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Suthat Liangpunsakul, MD

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Gastroenterology

Associate Professor of Medicine; Associate Professor of Biochemistry & Molecular Biology; Adjunct Associate Professor, School of Public Health
Associate Professor in Biochemistry and Molecular Biology

Academic Office

University Hospital, Suite 4100
550 University Blvd
Indianapolis IN 46202-5250 Map

Contact Information

Phone: (317) 988-3232
Fax: (317) 274-2091
Email:

Bio

Dr. Liangpunsakul is a guest lecturer for Epidemiology of Chronic Disease (P610: For Grad Students in Public Health Program)

Research Interests

Mechanism of alcoholic and non alcoholic liver disease, Serum markers for excessive alcohol consumption, Metabolic syndrome in post liver transplantation

Clinical Interests

End stage liver disease, cirrhosis, Alcoholic Liver Disease

Education and Training

Fellowship Indiana University School of Medicine
Residency University of Illinois at Chicago
Medicine (M.D.) Prtnce Of Songkhla University

Board Certifications

Internal Medicine
Gastroenterology
Transplant Hepatology

Publications (54)¹

Dissociation between diurnal cycles in locomotor activity, feeding behavior and hepatic PERIOD2 expression in chronic alcohol-fed mice.
Journal: Alcohol (Fayetteville, N.Y.)
Authors: Zhou P; Werner JH; Lee D; Sheppard AD; Liangpunsakul S; Duffield GE;
Publication Date: 2015 Apr 23

Abstract

Chronic alcohol consumption contributes to fatty liver disease. Our studies revealed that the hepatic circadian clock is disturbed in alcohol-induced hepatic steatosis, and effects of chronic alcohol administration upon the clock itself may contribute to steatosis. We extended these findings to explore the effects of chronic alcohol treatment on daily feeding and locomotor activity patterns. Mice were chronically pair-fed ad libitum for 4 weeks using the Lieber-DeCarli liquid diet, with calorie-controlled liquid and standard chow diets as control groups. Locomotor activity, feeding activity, and real-time bioluminescence recording of PERIOD2::LUCIFERASE expression in tissue explants were measured. Mice on liquid control and chow diets exhibited normal profiles of locomotor activity, with a ratio of 22:78% day/night activity and a peak during early night. This pattern was dramatically altered in alcohol-fed mice, marked by a 49:51% ratio and the absence of a distinct peak. While chow-diet fed mice had a normal 24:76% ratio of feeding activity, with a peak in the early night, this pattern was dramatically altered in both liquid-diet groups: mice had a 43:57% ratio, and an absence of a distinct peak. Temporal differences were also observed between the two liquid-diet groups during late day. Cosinor analysis revealed a ~4-h and ~6-h shift in the alcohol-fed group feeding and locomotor activity rhythms, respectively. Analysis of hepatic PER2 expression revealed that the molecular clock in alcohol-fed and control liquid-diet mice was shifted by ~11 h and ~6 h, respectively. No differences were observed in suprachiasmatic nucleus explants, suggesting that changes in circadian phase in the liver were generated independently from the central clock. These results suggest that chronic alcohol consumption and a liquid diet can differentially modulate the daily rhythmicity of locomotor and feeding behaviors, aspects that might contribute to disturbances in the circadian timing system and development of hepatic steatosis.
View details for PubMedID 25960184
Novel serum biomarkers for detection of excessive alcohol use.
Journal: Alcoholism, clinical and experimental research
Authors: Liangpunsakul S; Lai X; Ross RA; Yu Z; Modlik E; Westerhold C; Heathers L; Paul R; O'Connor S; Crabb DW; Witzmann F;
Publication Date: 2015 Feb 19

Abstract

Construct interview that correctly identifies those with alcohol use disorder have limitation, especially when the subjects are motivated to minimize the magnitude of drinking behavior. Current laboratory tests to detect excessive alcohol consumption are limited by marginal sensitivity/specificity. Excessive drinking has been shown to affect several organ systems, which may be reflected in changes in quantity of plasma proteins. Our aim was to employ novel proteomic analyses to identify potential markers for excessive alcohol use.
View details for PubMedID 25704570
Proteomic profiling of human sera for discovery of potential biomarkers to monitor abstinence from alcohol abuse.
Journal: Electrophoresis
Authors: Lai X; Liangpunsakul S; Li K; Witzmann FA;
Publication Date: 2015 Jan 22

Abstract

Although numerous biomarkers or biomarker candidates have been discovered to detect levels of drinking and intervals of time after last drinking episode, only a few biomarkers have been applied to monitor abstinence in a longer interval (=6 wks) from alcohol abuse. Considering sample sources, sensitivity, and specificity, new biomarkers from blood with better accuracy are needed. To address this, serum proteomic profiles were compared between pre- and post- treatment samples from subjects seeking treatment for alcohol abuse and dependence in an intensive 6wk daily outpatient program using high-abundance plasma protein immunodepletion and LC-MS/MS techniques. Protein identification, quantification, candidate biomarker selection, and prioritization analyses were carried out. Among the 246 quantified serum proteins, abundance of 13 and 45 proteins in female and male subjects were significantly changed (p = 0.05), respectively. Of these biomarker candidate proteins, 2 (female) and 8 (male) proteins were listed in category 1, with high area under the receiver operating characteristic curve, sensitivity, specificity, and fold change. In summary, several new biomarker candidates have been identified to monitor abstinence from alcohol abuse.
View details for PubMedID 25475211
A snapshot of the hepatic transcriptome: ad libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats.
Journal: PloS one
Authors: Klein JD; Sherrill JB; Morello GM; San Miguel PJ; Ding Z; Liangpunsakul S; Liang T; Muir WM; Lumeng L; Lossie AC;
Publication Date: 2014 Dec 26

Abstract

Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P) rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (~ 7.43 g ethanol/kg/day) in inbred alcohol-preferring (iP10a) rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake.
View details for PubMedID 25542004
Sestrin 3 Protein Enhances Hepatic Insulin Sensitivity by Direct Activation of the mTORC2-Akt Signaling.
Journal: Diabetes
Authors: Tao R; Xiong X; Liangpunsakul S; Dong XC;
Publication Date: 2014 Nov 5

Abstract

Sestrin proteins have been implicated in multiple biological processes including resistance to oxidative and genotoxic stresses, protection against aging-related pathologies, and promotion of metabolic homeostasis; however, the underlying mechanisms are incompletely understood. Some evidence suggests that sestrins may inhibit mTORC1 (mechanistic target of rapamycin complex 1) through inhibition of RagA/B GTPases or activation of AMPK; however, whether sestrins are also involved in mTORC2 regulation and function is unclear. To investigate the functions and mechanisms of Sestrin 3 (Sesn3), we generated Sesn3 liver-specific transgenic and knockout mice. Our data show that Sesn3 liver-specific knockout mice exhibit insulin resistance and glucose intolerance, and Sesn3 transgenic mice were protected against insulin resistance induced by a high-fat diet. Using AMPK liver-specific knockout mice, we demonstrate that the Sesn3 insulin-sensitizing effect is largely independent of AMPK. Biochemical analysis reveals that Sesn3 interacts with and activates mTORC2 and subsequently stimulates Akt phosphorylation at Ser473. These findings suggest that Sesn3 can activate Akt via mTORC2 to regulate hepatic insulin sensitivity and glucose metabolism.
View details for PubMedID 25377878
Relationship between serum leptin and chronic obstructive pulmonary disease in US adults: results from the third National Health and Nutrition Examination Survey.
Journal: Journal of investigative medicine : the official publication of the American Federation for Clinical Research
Authors: Sueblinvong V; Liangpunsakul S;
Publication Date: 2014 Oct

Abstract

Recent studies suggest an important role for leptin in respiratory immune responses and pathogenesis of inflammatory respiratory diseases. There has been an interest to explore whether leptin plays any role in the pathogenesis of chronic obstructive pulmonary disease (COPD).
View details for PubMedID 25118115
Increasing serum pre-adipocyte factor-1 (Pref-1) correlates with decreased body fat, increased free fatty acids, and level of recent alcohol consumption in excessive alcohol drinkers.
Journal: Alcohol (Fayetteville, N.Y.)
Authors: Liangpunsakul S; Bennett R; Westerhold C; Ross RA; Crabb DW; Lai X; Witzmann FA;
Publication Date: 2014 Sep 28

Abstract

Patients with alcoholic liver disease have been reported to have a significantly lower percentage of body fat (%BF) than controls. The mechanism for the reduction in %BF in heavy alcohol users has not been elucidated. In adipose tissue, Pref-1 is specifically expressed in pre-adipocytes but not in adipocytes. Pref-1 inhibits adipogenesis and elevated levels are associated with reduced adipose tissue mass. We investigated the association between serum Pref-1 and %BF, alcohol consumption, and serum free fatty acids (FFA) in a well-characterized cohort of heavy alcohol users compared to controls. One hundred forty-eight subjects were prospectively recruited. The Time Line Follow-Back (TLFB) questionnaire was used to quantify the amount of alcohol consumed over the 30-day period before their enrollment. Anthropometric measurements were performed to calculate %BF. Serum Pref-1 and FFA were measured. Fifty-one subjects (mean age 32 ± 9 years, 88% men) were non-excessive drinkers whereas 97 were excessive drinkers (mean age 41 ± 18 years, 69% men). Compared to non-excessive drinkers, individuals with excessive drinking had significantly higher levels of Pref-1 (p<0.01), FFA (p < 0.001), and lower %BF (p = 0.03). Serum levels of Pref-1 were associated with the amount of alcohol consumed during the previous 30 days. Serum Pref-1 was negatively correlated with %BF, but positively associated with serum FFA. Our data suggest that elevated Pref-1 levels in excessive drinkers might inhibit the expansion of adipose tissue, decreasing %BF in alcoholics. Further work is needed to validate these findings and to better understand the role of Pref-1 and its clinical significance in subjects with heavy alcohol use.
View details for PubMedID 25449367
Cirrhotic cardiomyopathy: review of pathophysiology and treatment.
Journal: Hepatology international
Authors: Chayanupatkul M; Liangpunsakul S;
Publication Date: 2014 Jul

Abstract

Cirrhotic cardiomyopathy is a cardiac condition observed in patients with cirrhotic regardless of the etiologies. It is characterized by the impaired systolic response to physical stress, diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. Its pathophysiology and clinical significance has been a focus of various researchers for the past decades. The impairment of ß-adrenergic receptor, the increase in endogenous cannabinoids, the presence of cardiosuppressants such as nitric oxide and inflammatory cytokines are the proposed mechanisms of systolic dysfunction. The activation of cardiac renin-angiotensin system and salt retention play the role in the development of cardiac hypertrophy and impaired diastolic function. QT interval prolongation, which is observed in 40-50 % of cirrhotic patients, occurs as a result of the derangement in membrane fluidity and ion channel defect. The increased recognition of this disease will prevent the complications of overt heart failure after procedures such as transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Better understandings of the pathogenesis and pathology of cirrhotic cardiomyopathy is crucial in developing more accurate diagnostic tools and specific treatments of this condition.
View details for PubMedID 25221635
Trends in Alcoholic Hepatitis-related Hospitalizations, Financial Burden, and Mortality in the United States.
Journal: Journal of clinical gastroenterology
Authors: Jinjuvadia R; Liangpunsakul S; for the Translational Research and Evolving Alcoholic Hepatitis Treatment Consortium;
Publication Date: 2014 Jun 25

Abstract

Alcoholic hepatitis (AH) is the most florid manifestation of alcoholic liver disease which accounts for significant morbidity, mortality, and financial burden. Aim of this study is to evaluate temporal trend of hospitalizations from AH and evaluate its financial impact.
View details for PubMedID 25198164
Role of cardiac catheterization and percutaneous coronary intervention in the preoperative assessment and management of patients before orthotopic liver transplantation.
Journal: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
Authors: Maddur H; Bourdillon PD; Liangpunsakul S; Joseph Tector A; Fridell JA; Ghabril M; Lacerda MA; Bourdillon C; Shen C; Kwo PY;
Publication Date: 2014 Jun

Abstract

Limited data regarding the optimal risk assessment strategy for evaluating candidates for orthotopic liver transplantation (OLT) exist. Our center has adopted a policy of performing cardiac catheterization (CATH) in patients with predefined risk factors, and this is followed by percutaneous coronary intervention (PCI) when it is indicated, even in the presence of negative stress test findings. The aim of this single-center, retrospective study of all patients who underwent OLT between 2000 and 2010 was to assess the effect of our policy on cardiovascular (CV) complications and survival rates after OLT. Data, including 1-year all-cause and CV mortality, postoperative myocardial infarctions (MIs), and frequencies of CATH and PCI, were abstracted. The study was divided into 3 subperiods to reflect the changes in policy over this period: (A) 2000-2004, (B) 2005-2008, and (C) 2009-2010. One thousand two hundred twenty-one patients underwent OLT between 2000 and 2010. The rate of catheterization increased during the 3 time periods (P?
View details for PubMedID 24648247
Deep vein thrombosis and pulmonary embolism in cirrhotic patients: systematic review.
Journal: World journal of gastroenterology : WJG
Authors: Aggarwal A; Puri K; Liangpunsakul S;
Publication Date: 2014 May 21

Abstract

Patients with liver cirrhosis were traditionally believed to be protected against development of blood clots. Lately, studies have shown that these patients may probably be at an increased risk of venous thrombotic complications. Although the hemostatic changes in the chronic liver disease patients and the factors that may predict bleeding vs thrombotic complications remains an area of active research, it is believed that the coagulation cascade is delicately balanced in these patients because of parallel reduced hepatic synthesis of pro and anticoagulant factors. Thrombotic state in cirrhotic patients is responsible for not only portal or non-portal thrombosis [deep vein thrombosis (DVT) and pulmonary embolism (PE)]; it has also been associated with progression of liver fibrosis. The use of anticoagulants in cirrhosis patients is a challenging, and often a scary situation. This review summarizes the current literature on the prevalence of venous thrombosis (DVT and PE), risk factors and safety of prophylactic and therapeutic anticoagulation in patients with chronic liver disease.
View details for PubMedID 24914335
The inhibitory effect of ethanol on Sestrin3 in the pathogenesis of ethanol-induced liver injury.
Journal: American journal of physiology. Gastrointestinal and liver physiology
Authors: Kang X; Petyaykina K; Tao R; Xiong X; Dong XC; Liangpunsakul S;
Publication Date: 2014 May 15

Abstract

Sestrins (Sesns) are a family of stress-sensitive genes that have been suggested to regulate lipid metabolism. Chronic ethanol feeding is known to cause lipid accumulation in hepatocytes. This study was designed to investigate the role of Sesn3 in the pathogenesis of alcohol-induced hepatic steatosis. We demonstrated that ethanol inhibited the expression of Sesn3 in VL-17A cells. Overexpression of Sesn3 ameliorated triglyceride accumulation; downregulation using short hairpin RNA significantly deteriorated triglyceride accumulation in these cells. The expression of Sesn3 was also reduced in mice fed with ethanol for 4 wk. Overexpression of Sesn3 prevented hepatic steatosis, whereas knockdown of Sesn3 worsened hepatic steatosis in ethanol-fed mice. Overexpression of Sesn3 significantly reduced the expression of genes encoding for lipid synthesis through AMPK pathway. Overexpression of Sesn3 augmented the effect of ethanol on phospho-p70 S6 kinase. The levels of hepatic light chain 3, a marker for autophagy, expression were significantly decreased in ethanol-fed mice after Sesn3 gene was knocked down. Our findings suggest that inhibitory effect of ethanol on Sesn3 may play an important role in the development of ethanol-induced fatty liver.
View details for PubMedID 24833709
The alcoholic hepatitis histologic score: structured prognostic biopsy evaluation comes to alcoholic hepatitis.
Journal: Gastroenterology
Authors: Liangpunsakul S; Kleiner DE;
Publication Date: 2014 Mar 25
Past exposure to hepatitis B: a risk factor for increase in mortality?
Journal: Journal of clinical gastroenterology
Authors: Jinjuvadia R; Liangpunsakul S; Antaki F;
Publication Date: 2014 Mar

Abstract

Chronic hepatitis B has been shown to increase mortality, but association of past exposure to hepatitis B and mortality has not been studied well. The aim of this study was to evaluate the risk of overall and liver-related mortality in individuals with past exposure to hepatitis B.
View details for PubMedID 23751854
The association between metabolic syndrome and hepatocellular carcinoma: systemic review and meta-analysis.
Journal: Journal of clinical gastroenterology
Authors: Jinjuvadia R; Patel S; Liangpunsakul S;
Publication Date: 2014 Feb

Abstract

The metabolic syndrome (MetS) and/or its individual components have been linked to the development of cancer. Recent studies have suggested a similar link to hepatocellular carcinoma (HCC). The aim of this study was to evaluate the direction and magnitude of the association between the MetS and HCC.
View details for PubMedID 24402120
Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis.
Journal: Scientific reports
Authors: Zhou P; Ross RA; Pywell CM; Liangpunsakul S; Duffield GE;
Publication Date: 2014 Jan 16

Abstract

To investigate the role of the circadian clock in the development of alcohol-induced fatty liver disease we examined livers of mice chronically alcohol-fed over 4-weeks that resulted in steatosis. Here we show time-of-day specific changes in expression of clock genes and clock-controlled genes, including those associated with lipid and bile acid regulation. Such changes were not observed following a 1-week alcohol treatment with no hepatic lipid accumulation. Real-time bioluminescence reporting of PERIOD2 protein expression suggests that these changes occur independently of the suprachiasmatic nucleus pacemaker. Further, we find profound time-of-day specific changes to the rhythmic synthesis/accumulation of triglycerides, cholesterol and bile acid, and the NAD/NADH ratio, processes that are under clock control. These results highlight not only that the circadian timekeeping system is disturbed in the alcohol-induced hepatic steatosis state, but also that the effects of alcohol upon the clock itself may actually contribute to the development of hepatic steatosis.
View details for PubMedID 24430730
Association between metabolic syndrome and its individual components with viral hepatitis B.
Journal: The American journal of the medical sciences
Authors: Jinjuvadia R; Liangpunsakul S;
Publication Date: 2014 Jan

Abstract

The association between hepatitis B and metabolic syndrome (MetS) has not been well described. Overall epidemiologic evidences for this association have suggested conflicting results. The aim this study was to determine the association between hepatitis B infection and MetS using large U.S. population database, the Third National Health and Nutrition Examination Survey.
View details for PubMedID 23514672
Renal failure in cirrhosis: is it time to change the diagnosis and classification?
Journal: American journal of nephrology
Authors: Liangpunsakul S; Agarwal R;
Publication Date: 2013 Oct 5
Adult diffuse hepatic hemangiomatosis: a rare cause of dilated cardiomyopathy and sudden cardiac arrest.
Journal: Journal of general internal medicine
Authors: Supakul R; Vakili ST; Liangpunsakul S;
Publication Date: 2013 Jul 19
Activation of carbohydrate response element-binding protein by ethanol.
Journal: Journal of investigative medicine : the official publication of the American Federation for Clinical Research
Authors: Liangpunsakul S; Ross RA; Crabb DW;
Publication Date: 2013 Feb

Abstract

Carbohydrate response element-binding protein (ChREBP) is a transcription factor involved in hepatic lipogenesis. Its function is in part under the control of AMP-activated protein kinase (AMPK) and protein phosphatase 2A (PP2A). Given known effects of ethanol on AMPK and PP2A, it is plausible that ethanol might enhance fatty acid synthesis by increasing the activity of ChREBP. We hypothesized that another potential pathway of ethanol-induced hepatic steatosis is mediated by activation of ChREBP.
View details for PubMedID 23266705
Prevalence and morbidity associated with muscle cramps in patients with cirrhosis.
Journal: The American journal of medicine
Authors: Chatrath H; Liangpunsakul S; Ghabril M; Otte J; Chalasani N; Vuppalanchi R;
Publication Date: 2012 Jul 24

Abstract

Patients with cirrhosis often experience muscle cramps with varying severity. We investigated the factors associated with the prevalence and morbidity associated with muscle cramps.
View details for PubMedID 22835465
Chronic free-choice drinking in crossed high alcohol preferring mice leads to sustained blood ethanol levels and metabolic tolerance without evidence of liver damage.
Journal: Alcoholism, clinical and experimental research
Authors: Matson L; Liangpunsakul S; Crabb D; Buckingham A; Ross RA; Halcomb M; Grahame N;
Publication Date: 2012 Jul 3

Abstract

Crossed high alcohol preferring (cHAP) mice were selectively bred from a cross of the HAP1 × HAP2 replicate lines, and we demonstrate blood ethanol concentrations (BECs) during free-choice drinking that are reminiscent of those observed in alcohol-dependent humans. Therefore, this line may provide an unprecedented opportunity to learn about the consequences of excessive voluntary ethanol (EtOH) consumption, including metabolic tolerance and liver pathology. Cytochrome p450 2E1 (CYP2E1) induction plays a prominent role in driving both metabolic tolerance and EtOH-induced liver injury. In this report, we sought to characterize cHAP drinking by assessing whether pharmacologically relevant BEC levels are sustained throughout the active portion of the light-dark cycle. Given that cHAP intakes and BECs are similar to those observed in mice given an EtOH liquid diet, we assessed whether free-choice exposure results in metabolic tolerance, hepatic enzyme induction, and hepatic steatosis.
View details for PubMedID 22757960
What should we recommend to our patients with NAFLD regarding alcohol use?
Journal: The American journal of gastroenterology
Authors: Liangpunsakul S; Chalasani N;
Publication Date: 2012 Jul

Abstract

It is generally recommended that patients with nonalcoholic fatty liver disease (NAFLD) not consume alcohol. However, because these patients are at increased cardiovascular risk, and light to moderate alcohol consumption may have hepatic benefits in people with or at risk for NAFLD, this recommendation may be ill-advised. We reviewed the literature on alcohol consumption and NAFLD and conclude that (i) heavy consumption has many harmful effects, including those on the liver, and should be discouraged whether a person has NAFLD or not; (ii) it is unknown whether cardiovascular and metabolic benefits of light to moderate consumption observed in the general population extend to those with NAFLD; (iii) epidemiological and cohort studies suggesting that light to moderate drinking may have hepatic benefits are largely cross-sectional and used surrogate end points; and (iv) until further data from rigorous prospective studies become available, people with NAFLD should avoid alcohol of any type or amount.
View details for PubMedID 22764020
Imipramine blocks ethanol-induced ASMase activation, ceramide generation, and PP2A activation, and ameliorates hepatic steatosis in ethanol-fed mice.
Journal: American journal of physiology. Gastrointestinal and liver physiology
Authors: Liangpunsakul S; Rahmini Y; Ross RA; Zhao Z; Xu Y; Crabb DW;
Publication Date: 2011 Dec 22

Abstract

Our previous data showed the inhibitory effect of ethanol on AMP-activated protein kinase phosphorylation, which appears to be mediated, in part, through increased levels of hepatic ceramide and activation of protein phosphatase 2A (Liangpunsakul S, Sozio MS, Shin E, Zhao Z, Xu Y, Ross RA, Zeng Y, Crabb DW. Am J Physiol Gastrointest Liver Physiol 298: G1004-G1012, 2010). The effect of ethanol on AMP-activated protein kinase phosphorylation was reversed by imipramine, suggesting that the generation of ceramide via acid sphingomyelinase (ASMase) is stimulated by ethanol. In this study, we determined the effects of imipramine on the development of hepatic steatosis, the generation of ceramide, and downstream effects of ceramide on inflammatory, insulin, and apoptotic signaling pathways, in ethanol-fed mice. The effect of ethanol and imipramine (10 µg/g body wt ip) on ceramide levels, as well as inflammatory, insulin, and apoptotic signaling pathways, was studied in C57BL/6J mice fed the Lieber-DeCarli diet. Ethanol-fed mice developed the expected steatosis, and cotreatment with imipramine for the last 2 wk of ethanol feeding resulted in improvement in hepatic steatosis. Ethanol feeding for 4 wk induced impaired glucose tolerance compared with controls, and this was modestly improved with imipramine treatment. There was a significant decrease in total ceramide concentrations in response to imipramine in ethanol-fed mice treated with and without imipramine (287 ± 11 vs. 348 ± 12 pmol/mg tissue). The magnitude and specificity of inhibition on each ceramide species differed. A significant decrease was observed for C16 (28 ± 3 vs. 33 ± 2 pmol/mg tissue) and C24 (164 ± 9 vs. 201 ± 4 pmol/mg tissue) ceramide. Ethanol feeding increased the levels of the phosphorylated forms of ERK slightly and increased phospho-p38 and phospho-JNK substantially. The levels of phospho-p38 and phospho-JNK were reduced by treatment with imipramine. The activation of ASMase and generation of ceramide in response to ethanol feeding may underlie several effects of ethanol. ASMase inhibitors may be considered as a therapeutic target for alcohol-induced hepatic steatosis and activation of stress kinases.
View details for PubMedID 22194417
Clinical characteristics and mortality of hospitalized alcoholic hepatitis patients in the United States.
Journal: Journal of clinical gastroenterology
Authors: Liangpunsakul S;
Publication Date: 2011 Sep

Abstract

Alcoholic hepatitis (AH) is the most florid manifestation of alcoholic liver disease. In this study, we examined the clinical characteristics and risk factors associated with mortality in hospitalized AH patients in the United States using the 2007 Nationwide inpatient sample of the Healthcare Cost and Utilization Project.
View details for PubMedID 21085006
Ethanol impairs differentiation of human adipocyte stromal cells in culture.
Journal: Alcoholism, clinical and experimental research
Authors: Crabb DW; Zeng Y; Liangpunsakul S; Jones R; Considine R;
Publication Date: 2011 May 20

Abstract

Bioinformatic resources suggest that adipose tissue expresses mRNAs for alcohol dehydrogenases (ADHs) and ALDH2, and epidemiological studies indicate that heavy alcohol use reduces adipose tissue mass. We therefore characterized the expression of alcohol metabolizing enzymes in human, rat and mouse adipose tissue, preadipocytes, and adipocytes, the ability of adipocytes to metabolize ethanol, and the effects of ethanol on differentiation of human adipose stromal cells (hASCs).
View details for PubMedID 21599713
Alcoholic-induced hepatic steatosis--role of ceramide and protein phosphatase 2A.
Journal: Translational research : the journal of laboratory and clinical medicine
Authors: Supakul R; Liangpunsakul S;
Publication Date: 2011 Apr 20

Abstract

The mechanisms underlying alcohol-induced hepatic steatosis are complex, involving the disturbance of several signaling pathways. We have gained a better understanding of the role of the innate immune system in the liver and its effects on lipid metabolism and uncovered a number of circulating factors that can influence the response of the liver to ethanol. In this report, we will focus on the potential role of ceramide on AMP-activated protein kinase, as a mediator of alcohol-induced hepatic steatosis.
View details for PubMedID 21757150
Serum vitamin D concentrations and unexplained elevation in ALT among US adults.
Journal: Digestive diseases and sciences
Authors: Liangpunsakul S; Chalasani N;
Publication Date: 2011 Apr 19

Abstract

Low serum levels of vitamin D are associated with metabolic syndrome. Participants in NHANES III with unexplained elevation in ALT levels have high prevalence of metabolic syndrome. We hypothesized that the serum concentrations of vitamin D were inversely associated with unexplained elevation in ALT.
View details for PubMedID 21503677
Ethanol metabolism by HeLa cells transduced with human alcohol dehydrogenase isoenzymes: control of the pathway by acetaldehyde concentration.
Journal: Alcoholism, clinical and experimental research
Authors: Matsumoto M; Cyganek I; Sanghani PC; Cho WK; Liangpunsakul S; Crabb DW;
Publication Date: 2011 Jan

Abstract

Human class I alcohol dehydrogenase 2 isoenzymes (encoded by the ADH1B locus) have large differences in kinetic properties; however, individuals inheriting the alleles for the different isoenzymes exhibit only small differences in alcohol elimination rates. This suggests that other cellular factors must regulate the activity of the isoenzymes.
View details for PubMedID 21166830
Hepatic and extrahepatic cancer in cirrhosis: a longitudinal cohort study.
Journal: The American journal of gastroenterology
Authors: Berman K; Tandra S; Vuppalanchi R; Ghabril M; Sandrasegaran K; Nguyen J; Caffrey H; Liangpunsakul S; Lumeng L; Kwo P; Chalasani N;
Publication Date: 2010 Dec 21

Abstract

We conducted a retrospective cohort study in cirrhotic patients to understand (i) the risk of developing hepatocellular carcinoma (HCC) after an initial negative screening computed tomography (CT) scan and its relationship with underlying etiology and (ii) the risk of extrahepatic cancers (EHCs).
View details for PubMedID 21179013
Ethanol-induced alterations in fatty acid-related lipids in serum and tissues in mice.
Journal: Alcoholism, clinical and experimental research
Authors: Zhao Z; Yu M; Crabb D; Xu Y; Liangpunsakul S;
Publication Date: 2010 Nov 8

Abstract

Chronic alcohol consumption is a major factor for several human diseases, and alcoholism is associated with a host of societal problems. One of the major alcohol-induced metabolic changes is the increased NADH levels, which reduces glucose synthesis and increases fatty acid (FA) synthesis. Probably more important is the induction of FA synthesizing enzymes under the control of sterol regulatory element binding proteins (SREBP), plus increased malonyl-CoA, which blocks FA entry to the mitochondria for oxidation. The changes in FA-related lipids, particularly lysophospholipids and ceramides (Cers), in different tissues in ethanol-fed mice have not been reported.
View details for PubMedID 21058963
The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis.
Journal: Seminars in liver disease
Authors: Sozio MS; Liangpunsakul S; Crabb D;
Publication Date: 2010 Oct 19

Abstract

Hepatic steatosis is now understood to play an important role in the development of advanced liver disease. Alcoholic and nonalcoholic fatty liver each begin with the accumulation of lipids in the liver. Lipid accumulation in the liver can occur through maladaptations of fatty acid uptake (either through dietary sources or from fat tissue), fatty acid synthesis, fatty acid oxidation, or export of lipids from the liver. Alterations in mechanisms of fatty acid uptake through both dietary uptake and lipolysis in adipose tissue can contribute to the pathogenesis of both disorders, as can effects on fatty acid transporters. Effects on lipid synthesis in alcoholic and nonalcoholic fatty liver involve the endoplasmic reticulum (ER) stress response, homocysteine metabolism pathway, and different transcription factors regulating genes in the lipid synthesis pathway. Fatty acid oxidation, through effects on AMP-activated protein kinase (AMPK), adiponectin, peroxisome proliferator-activated receptors (PPARs), and mitochondrial function is predominantly altered in alcoholic liver disease, although studies suggest that activation of this pathway may improve nonalcoholic fatty liver disease. Finally, changes in fatty acid export, through effects on apolipoprotein B and microsomal transport protein are seen in both diseases. Thus, the similarities and differences in the mechanism of fat accumulation in the liver in nonalcoholic and alcoholic liver disease are explored in detail.
View details for PubMedID 20960377
Relationship among alcohol intake, body fat, and physical activity: a population-based study.
Journal: Annals of epidemiology
Authors: Liangpunsakul S; Crabb DW; Qi R;
Publication Date: 2010 Sep

Abstract

Aside from fat, ethanol is the macronutrient with the greatest energy density. Whether the energy derived from ethanol affects body composition and fat mass is debatable. We investigated the relationship of alcohol intake, body composition, and physical activity in the U.S. population by using data from the Third National Health and Nutrition Examination Survey (NHANES III).
View details for PubMedID 20696406
Relationship between alcohol intake and dietary pattern: findings from NHANES III.
Journal: World journal of gastroenterology : WJG
Authors: Liangpunsakul S;
Publication Date: 2010 Aug 28

Abstract

To examine the association between macronutrient dietary patterns and alcohol consumption using the Third National Health and Nutritional Examination Survey III.
View details for PubMedID 20731019
Inhibitory effect of ethanol on AMPK phosphorylation is mediated in part through elevated ceramide levels.
Journal: American journal of physiology. Gastrointestinal and liver physiology
Authors: Liangpunsakul S; Sozio MS; Shin E; Zhao Z; Xu Y; Ross RA; Zeng Y; Crabb DW;
Publication Date: 2010 Mar 11

Abstract

Ethanol treatment of cultured hepatoma cells and of mice inhibited the activity of AMP-activated protein kinase (AMPK). This study shows that the inhibitory effect of ethanol on AMPK phosphorylation is exerted through the inhibition of the phosphorylation of upstream kinases and the activation of protein phosphatase 2A (PP2A).Inhibition of AMPK phosphorylation by palmitate was attributed to ceramide-dependent PP2A activation. We hypothesized that the inhibitory effect of ethanol on AMPK phosphorylation was mediated partly through the generation of ceramide. The effect of ethanol and inhibitors of ceramide synthesis on AMPK phosphorylation, ceramide levels, and PP2A activity were assessed in rat hepatoma cells (H4IIEC3). The effect of ethanol on hepatic ceramide levels was also studied in C57BL/6J mice fed the Lieber-DeCarli diet. In H4IIEC3 cells, ceramide reduced AMPK phosphorylation when they were treated for between 4 and 12 h. The basal level of AMPK phosphorylation in hepatoma cells was increased with the treatment of ceramide synthase inhibitor, fumonisin B1. Ethanol treatment significantly increased cellular ceramide content and PP2A activity by approximately 18-23%, when the cells were treated with ethanol for between 4 and 12 h. These changes in intracellular ceramide concentrations and PP2A activity correlated with the time course over which ethanol inhibited AMPK phosphorylation. The activation of PP2A and inhibition of AMPK phosphorylation caused by ethanol was attenuated by fumonisin B1 and imipramine, an acid sphingomyelinase (SMase) inhibitor. There was a significant increase in the levels of ceramide and acid SMase mRNA in the livers of ethanol-fed mice compared with controls. We concluded that the effect of ethanol on AMPK appears to be mediated in part through increased cellular levels of ceramide and activation of PP2A.
View details for PubMedID 20224005
Relationship between alcohol drinking and aspartate aminotransferase:alanine aminotransferase (AST:ALT) ratio, mean corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), and apolipoprotein A1 and B in the U.S. population.
Journal: Journal of studies on alcohol and drugs
Authors: Liangpunsakul S; Qi R; Crabb DW; Witzmann F;
Publication Date: 2010 Mar

Abstract

The misuse of alcohol, even at levels just above two drinks per day, is a public health problem, but identifying patients with this potentially unhealthy drinking is hindered by the lack of tests. Several blood tests, such as those testing for gamma-glutamyl transpeptidase (GGT) or mean corpuscular volume (MCV), are among the commonly used markers to identify very heavy drinking, but combinations of these markers have rarely been tested in lighter drinkers. We examined the relationship between alcohol drinking and the levels of these markers in a national population-based study composed primarily of lighter drinkers.
View details for PubMedID 20230722
A proteomic workflow for discovery of serum carrier protein-bound biomarker candidates of alcohol abuse using LC-MS/MS.
Journal: Electrophoresis
Authors: Lai X; Liangpunsakul S; Crabb DW; Ringham HN; Witzmann FA;
Publication Date: 2009 Jun

Abstract

The diagnosis and care of patients with alcohol abuse and dependence is hampered by a lack of sensitive and specific screening and monitoring tests. Proteomics is a good approach to search for biomarkers of alcohol abuse. Serum carrier protein-bound proteins have attracted significant interest because they remain a relatively un-mined region of the proteome. In the present study, a proteomic workflow including LC-MS/MS with enrichment of serum carrier protein-bound biomarkers technique was applied to profile the changes in quality and quantity of serum carrier protein-bound proteins for the discovery of novel biomarker candidates of alcohol abuse. In total, 311 proteins identified with high confidence were discovered to be bound to serum carrier proteins. Complement isoforms, Ig fragments, and apolipoprotein family proteins are the main serum carrier-bound proteins. Protein quantification analysis with and without concern as to gender revealed that gender is a critical consideration for biomarker development in alcohol abuse. Identified proteins not previously associated with alcohol abuse include gelsolin, selenoprotein P, serotransferrin, tetranectin, hemopexin, histidine-rich glycoprotein, plasma kallikrein, and vitronectin. Altered abundance of these proteins suggests that they may be potential novel biomarkers for alcohol abuse.
View details for PubMedID 19544491
Serum Proteomic Profiles In Subjects with Heavy Alcohol Abuse.
Journal: Journal of proteomics & bioinformatics
Authors: Liangpunsakul S; Lai X; Ringham HN; Crabb DW; Witzmann FA;
Publication Date: 2009 May 20

Abstract

OBJECTIVES: The abuse of alcohol is a major public health problem, and the diagnosis and care of patients with alcohol abuse and dependence is hindered by the lack of tests that can detect dangerous levels of drinking or relapse during therapy. Gastroenterologists and other healthcare providers find it very challenging to obtain an accurate alcohol drinking history. We hypothesized that the effects of ethanol on numerous systems may well be reflected in changes in quantity or qualities of constituent or novel plasma proteins or protein fragments. Organ/tissue-specific proteins may be released into the blood stream when cells are injured by alcohol, or when systemic changes are induced by alcohol, and such proteins would be detected using a proteomic approach. The objective of this pilot study was to determine if there are plasma proteome profiles that correlate with heavy alcohol use. METHODS: Paired serum samples, before and after intensive alcohol treatment, were obtained from subjects who attended an outpatient alcohol treatment program. Serum proteomic profiles using MALDI -OTOF Mass Spectrometry were compared between pre- and post treatment samples. RESULTS: Of 16 subjects who enrolled in the study, 8 were females. The mean age of the study subjects was 49 yrs. The baseline laboratory data showed elevated AST (54 ± 37 IU/L), ALT (37 ± 19 IU/L), and MCV (99 ± 5 fl). Self-reported pre-treatment drinking levels for these subjects averaged 17 ± 7drinks/day and 103 ± 37 drinks/week. Mass spectrometry analyses showed a novel 5.9 kDa protein, a fragment of alpha fibrinogen, isoform 1, that might be might be a new novel marker for abusive alcohol drinking. CONCLUSIONS: We have shown in this pilot study that several potential protein markers have appeared in mass spectral profiles and that they may be useful clinically to determine the status of alcohol drinking by MALDI -OTOF mass spectrometry, especially a fragment of alpha fibrinogen, isoform 1. However, a large-scale study is needed to confirm and validate our current results.
View details for PubMedID 19672327
Effects of WY-14,643 on the phosphorylation and activation of AMP-dependent protein kinase.
Journal: Archives of biochemistry and biophysics
Authors: Liangpunsakul S; Wou SE; Wineinger KD; Zeng Y; Cyganek I; Jayaram HN; Crabb DW;
Publication Date: 2009 Feb 21

Abstract

AMP-dependent protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR) alpha facilitate fatty acid oxidation. We have shown that treatment of hepatoma cells with ethanol or feeding ethanol-containing diets to mice inhibited both PPARalpha and AMPK activity. Importantly, WY-14,643 reversed the development of fatty liver in alcohol-fed mice. Whether WY-14,643, a PPARalpha agonist, has any effects on AMPK is not known. The aim of this study was to investigate the effect of WY-14,643 on AMPK activity.
View details for PubMedID 19236843
What advice should be given to patients with NAFLD about the consumption of alcohol?
Journal: Nature clinical practice. Gastroenterology & hepatology
Authors: Sozio MS; Chalasani N; Liangpunsakul S;
Publication Date: 2008 Nov 18
Effect of ethanol on hydrogen peroxide-induced AMPK phosphorylation.
Journal: American journal of physiology. Gastrointestinal and liver physiology
Authors: Liangpunsakul S; Wou SE; Zeng Y; Ross RA; Jayaram HN; Crabb DW;
Publication Date: 2008 Oct 2

Abstract

AMP-activated protein kinase (AMPK) responds to oxidative stress. Previous work has shown that ethanol treatment of cultured hepatoma cells and of mice inhibited the activity of AMPK and reduced the amount of AMPK protein. Ethanol generates oxidative stress in the liver. Since AMPK is activated by reactive oxygen species, it seems paradoxical that ethanol would inhibit AMPK in the hepatoma cells. In an attempt to understand the mechanism whereby ethanol inhibits AMPK, we studied the effect of ethanol on AMPK activation by exogenous hydrogen peroxide. The effects of ethanol, hydrogen peroxide, and inhibitors of protein phosphatase 2A (PP2A) [either okadaic acid or PP2A small interference RNA (siRNA)] on AMPK phosphorylation and activity were examined in rat hepatoma cells (H4IIEC3) and HeLa cells. In H4IIEC3 cells, hydrogen peroxide (H(2)O(2), 1 mM) transiently increased the level of phospho-AMPK to 1.5-fold over control (P < 0.05). Similar findings were observed in HeLa cells, which do not express the upstream AMPK kinase, LKB1. H(2)O(2) markedly increased the phosphorylation of LKB1 in H4IIEC3 cells. Ethanol significantly inhibited the phosphorylation of PKC-zeta, LKB1, and AMPK caused by exposure to H(2)O(2). This inhibitory effect of ethanol required its metabolism. More importantly, the inhibitory effects of ethanol on H(2)O(2)-induced AMPK phosphorylation were attenuated by the presence of the PP2A inhibitor, okadaic acid, or PP2A siRNA. The inhibitory effect of ethanol on AMPK phosphorylation is exerted through the inhibition of PKC-zeta and LKB1 phosphorylation and the activation of PP2A.
View details for PubMedID 18832448
Gastrointestinal plasmacytoma presenting as gastrointestinal bleeding.
Journal: Clinical lymphoma & myeloma
Authors: Suvannasankha A; Abonour R; Cummings OW; Liangpunsakul S;
Publication Date: 2008 Oct

Abstract

Clinical manifestations of gastrointestinal (GI) involvement in multiple myeloma (MM) are uncommon. We report a case of plasmacytoma presenting as upper GI bleeding in a patient with a known diagnosis of MM. Gastrointestinal bleeding persists despite aggressive medical and endoscopic treatment. The aim of our report is to heighten the awareness of plasmacytoma as an etiology of GI bleeding in patients with MM. Abnormal hemostasis, specifically the imbalance in function of all major components of the coagulation cascade, increasing bleeding risk in patients with MM, is also discussed.
View details for PubMedID 18854287
Forestier disease: a rare cause of dysphagia.
Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Authors: Khashab MA; Liangpunsakul S;
Publication Date: 2008 Sep 27
Deep vein thrombosis and pulmonary embolism in cirrhosis patients.
Journal: Digestive diseases and sciences
Authors: Gulley D; Teal E; Suvannasankha A; Chalasani N; Liangpunsakul S;
Publication Date: 2008 Apr 29

Abstract

It is a commonly held notion that patients with cirrhosis do not suffer from deep vein thrombosis (DVT) or pulmonary embolism (PE) because they are naturally anticoagulated. However, to date, no studies have been carried out that objectively address this issue. We conducted a study to examine the relationship between cirrhosis and DVT/PE events.
View details for PubMedID 18443906
Nonalcoholic fatty liver disease as a component of the metabolic syndrome.
Journal: Current gastroenterology reports
Authors: Khashab MA; Liangpunsakul S; Chalasani N;
Publication Date: 2008 Feb

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver-related morbidity and mortality. The association between NAFLD and the metabolic syndrome is well established: the presence of the metabolic syndrome signifies advanced histology in NAFLD patients. Emerging data indicate that patients with NAFLD have a significantly higher prevalence of cardiovascular disease. This article reviews the definitions of the two syndromes, their association, and the cardiovascular risk conferred by both when they occur separately and together. This review also discusses management options for the syndromes, including treating the individual components of the metabolic syndrome in NAFLD patients.
View details for PubMedID 18417046
Role of hemoclips in the management of acute bleeding from a gastric stromal tumor: a case report and review of the literature.
Journal: Journal of medical case reports
Authors: Khashab MA; Cramer HM; Liangpunsakul S;
Publication Date: 2007 Nov 14

Abstract

Though gastrointestinal stromal tumors (GISTs) frequently present with gastrointestinal bleeding, the guidelines for the management and control of bleeding are unclear especially in patients who are not appropriate for surgical resection.
View details for PubMedID 18001470
Predictors of outcome in patients with unresectable hepatocellular carcinoma receiving transcatheter arterial chemoembolization.
Journal: Alimentary pharmacology & therapeutics
Authors: Shen H; Agarwal D; Qi R; Chalasani N; Liangpunsakul S; Lumeng L; Yoo H; Kwo P;
Publication Date: 2007 Aug 1

Abstract

Transcatheter arterial chemoembolization (TACE) has been shown to improve survival in patients with unresectable hepatocellular carcinoma (HCC).
View details for PubMedID 17635374
Etiology of new-onset jaundice: how often is it caused by idiosyncratic drug-induced liver injury in the United States?
Journal: The American journal of gastroenterology
Authors: Vuppalanchi R; Liangpunsakul S; Chalasani N;
Publication Date: 2007 Mar

Abstract

The epidemiology of acute drug-induced liver injury (DILI) in the United States has not been well studied. We conducted a study of adults with new-onset jaundice at a nonreferral community hospital to better understand the epidemiology of acute DILI.
View details for PubMedID 17156142
Acetaldehyde generating enzyme systems: roles of alcohol dehydrogenase, CYP2E1 and catalase, and speculations on the role of other enzymes and processes.
Journal: Novartis Foundation symposium
Authors: Crabb DW; Liangpunsakul S;
Publication Date: 2007

Abstract

Most acetaldehyde is generated in the liver by alcohol dehydrogenase (ADH) during ethanol metabolism. Polymorphic variants of these genes encode enzymes with altered kinetic properties, and pathophysiological effects of these variants may be mediated by accumulation of acetaldehyde. Two additional pathways of acetaldehyde generation are by the cytochrome P450 2E1 (CYP2E1) and catalase. While the amount of ethanol oxidized by these enzymes comprises a small fraction of total body ethanol clearance, the local formation of acetaldehyde by these enzymes may have important effects. Additional sources of acetaldehyde include other minor enzymes (nitric oxide synthase, other cytochrome P450s, P450 reductase, xanthine oxidoreductase) as well as non-enzymatic pathways (formation of hydroxyethyl radicals from the reaction of ethanol with hydroxyl radical, and its subsequent decomposition to acetaldehyde). Acetaldehyde may have effects locally (in the cells generating it), or when delivered to other cells by the blood stream or saliva, or by diffusion from the lumen of the gastrointestinal tract. The ultimate determinants of acetaldehyde toxicity include rates of its formation, rates of oxidation, and the capacity of cellular systems to prevent or repair chemical effects of acetaldehyde (e.g. formation of protein adducts or modification of nucleic acid bases).
View details for PubMedID 17590984
Alcohol and lipid metabolism.
Journal: Journal of gastroenterology and hepatology
Authors: Crabb DW; Liangpunsakul S;
Publication Date: 2006 Oct

Abstract

Hepatic lipid metabolism is controlled by several master transcription factors, in particular peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and sterol response element binding protein-1 (SREBP-1). Peroxisome proliferator-activated receptor-alpha is a receptor for free fatty acids (FFA), and can activate genes involved in transport, oxidation, and export of FFA. Sterol response element binding protein-1 is a sensor for the level of cholesterol in the liver, and is able to activate genes involved in synthesis of cholesterol and FFA. Chronic ethanol treatment of cells or animals inhibited PPAR-alpha function and activated SREBP. In addition, ethanol inhibited adenosine monophosphate-dependent protein kinase (AMPK). The AMPK controls fatty acid metabolism by inhibiting acetyl-coenzyme A carboxylase, reducing malonyl-coenzyme A, and thereby permitting fatty acid transport into and oxidation in the mitochondrion. Adenosine monophosphate-dependent protein kinase was inhibited in alcohol-treated animals and cells. The mechanisms by which ethanol affects AMPK and the transcription factors are as yet incompletely understood.
View details for PubMedID 16958674
Preprocedure patient values regarding sedation for colonoscopy.
Journal: Journal of clinical gastroenterology
Authors: Subramanian S; Liangpunsakul S; Rex DK;
Publication Date: 2005 Jul

Abstract

Adherence rates for screening colonoscopy remain low. There are little data describing pre-colonoscopy patient concepts, values, and preferences for sedation during colonoscopy. In this study, we sought to investigate preprocedure patient values regarding sedation use for colonoscopy.
View details for PubMedID 15942439
Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: a comparison with nonalcoholics.
Journal: Hepatology (Baltimore, Md.)
Authors: Liangpunsakul S; Kolwankar D; Pinto A; Gorski JC; Hall SD; Chalasani N;
Publication Date: 2005 May

Abstract

Alcohol consumption is known to induce hepatic CYP2E1 activity, but its effect on hepatic and intestinal CYP3A in humans is not known. We have conducted a study to compare the CYP2E1 and CYP3A activities in 20 individuals with moderate alcohol consumption and 20 gender-, race-. and body mass index (BMI)-matched nonalcoholics. Intravenous and oral midazolam (MDZ) clearances were used to measure the in vivo CYP3A activity, and chlorzoxazone (CHZ) oral clearance was used to assess in vivo CYP2E1 activity. Furthermore, we assessed the relationship between hepatic CYP2E1 and CYP3A activities and their messenger RNA (mRNA) expression in the peripheral lymphocytes. The systemic clearance (CL) of MDZ was not different between alcoholics (36.9 +/- 12 L/hr) and nonalcoholics (36.6 +/- 14.1; P = .9). The oral availability of MDZ was significantly lower in alcoholics than in the nonalcoholics (0.28 +/- .09 vs. 0.38 +/- .17, respectively, P = .03). The maximum serum concentration after oral midazolam dosing was significantly different between the 2 groups. CHZ CL was significantly higher in alcoholics than in nonalcoholics (31.5 +/- 11.9 vs. 23.4 +/- 8.7 L/hr, P < 0.05). CYP3A4 and CYP2E1 mRNA levels were not significantly different between the groups, and no correlation was observed between lymphocyte CYP mRNA and in vivo CYP activity. In conclusion, in individuals with moderate alcohol consumption, there was no alteration in the hepatic CYP3A activity, but the reduced midazolam oral bioavailability suggests that moderate alcohol consumption may cause intestinal CYP3A induction. Lymphocyte CYP2E1 and CYP3A4 mRNA levels did not correlate with CYP2E1 and CYP3A activities.
View details for PubMedID 15841467
Watermelon colon treated by argon plasma coagulation.
Journal: Gastrointestinal endoscopy
Authors: Chen SC; Liangpunsakul S; Rex DK;
Publication Date: 2005 Apr
Unexplained elevations in alanine aminotransferase in individuals with the metabolic syndrome: results from the third National Health and Nutrition Survey (NHANES III).
Journal: The American journal of the medical sciences
Authors: Liangpunsakul S; Chalasani N;
Publication Date: 2005 Mar

Abstract

Unexplained elevations in alanine aminotransferase (ALT) level have been suggested to signify the presence of nonalcoholic fatty liver disease (NAFLD) in adult NHANES III participants. In this study, we examined the relationship between unexplained elevations in ALT level and the metabolic syndrome and the relationship between unexplained elevations in ALT level and microalbuminuria.
View details for PubMedID 15767815