Elevated adiponectin serum levels in patients with chronic alcohol abuse rapidly decline during alcohol withdrawal

Buechler, Christa; Schäffler, Andréas; Johann, Monika; Neumeier, Markus; Köhl, Philip; Weiss, Thomas S.; Wodarz, Norbert; Kiefer, Paul; Hellerbrand, Claus

doi:10.1111/j.1440-1746.2008.05693.x

Cited by 37 publications

(28 citation statements)

References 31 publications

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“…ARL15 was previously shown to be associated with adiponectin levels, but the exact function of this gene is still unknown (Richards et al, 2009). Several studies have found that adiponectin levels are elevated in patients with chronic alcohol abuse (Buechler et al, 2009) and might also be associated with alcohol craving (Hillemacher et al, 2009). The enrichment analysis using HaploReg showed that SNPs identified at this locus in the COGA dataset predicted significant (p < 5.2 × 10 −4 ) enrichment of enhancers in H1 and leukemia cell lines.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families

Kapoor¹,

Wang²,

Wetherill

et al. 2014

Drug and Alcohol Dependence

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Background The age at onset of alcohol dependence (AD) is a critical moderator of genetic associations for alcohol dependence. The present study evaluated whether single nucleotide polymorphisms (SNPs) can influence the age at onset of AD in large high-risk families from the Collaborative Study on the Genetics of Alcoholism (COGA). Methods Genomewide SNP genotyping was performed in 1788 regular drinkers from 118 large European American families densely affected with alcoholism. We used a genome-wide Cox proportional hazards regression model to test for association between age at onset of AD and SNPs. Results This family-based analysis identified an intergenic SNP, rs2168784 on chromosome 3 that showed strong evidence of association (p= 5 × 10−9) with age at onset of AD among regular drinkers. Carriers of the minor allele of rs2168784 had 1.5 times the hazard of AD onset as compared with those homozygous for the major allele. By the age of 20 years, nearly 30% of subjects homozygous for the minor allele were alcohol dependent while only 19% of those homozygous for the major allele were. We also identified intronic SNPs in the ADP-ribosylation factor like 15 (ARL15) gene on chromosome 5 (P = 1.11 × 10−8) and the UTP20 small subunit (UTP20) gene on chromosome 12 (P = 4.32 × 10−8) that were associated with age at onset of AD. Conclusions This extended family based genome-wide cox-proportional hazards analysis identified several loci that might be associated with age at onset of AD.

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Section: Discussionmentioning

confidence: 99%

Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families

Kapoor¹,

Wang²,

Wetherill

et al. 2014

Drug and Alcohol Dependence

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“…Several reports have shown that ethanol feeding reduces the plasma adiponectin level in mice, rats, or micropigs (36,43,48). In contrast, some studies demonstrated that ethanol exposure increases the plasma adiponectin level in mice or patients with alcoholic hepatitis (5,11,44). Despite the controversial results, administration mouse recombinant adiponectin has been shown to attenuate alcohol-induced steatosis and inflammation (43).…”

Section: G554 Rosiglitazone Reverses Ethanol-induced Adipose Dysfunctionmentioning

confidence: 95%

Activation of peroxisome proliferator-activated receptor-γ by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice

Sun

Tang²,

Tan

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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The development of alcohol-induced fatty liver is associated with a reduction of white adipose tissue (WAT). Peroxisome proliferator-activated receptor (PPAR)-γ prominently distributes in the WAT and plays a crucial role in maintaining adiposity. The present study investigated the effects of PPAR-γ activation by rosiglitazone on lipid homeostasis at the adipose tissue-liver axis. Adult C57BL/6 male mice were pair fed liquid diet containing ethanol or isocaloric maltose dextrin for 8 wk with or without rosiglitazone supplementation to ethanol-fed mice for the last 3 wk. Ethanol exposure downregulated adipose PPAR-γ gene and reduced the WAT mass in association with induction of inflammation, which was attenuated by rosiglitazone. Ethanol exposure stimulated lipolysis but reduced fatty acid uptake capacity in association with dysregulation of lipid metabolism genes. Rosiglitazone normalized adipose gene expression and corrected ethanol-induced lipid dyshomeostasis. Ethanol exposure induced steatosis and upregulated inflammatory genes in the liver, which were attenuated by rosiglitazone. Hepatic peroxisomal fatty acid β-oxidation was suppressed by ethanol in associated with inhibition of acyl-coenzyme A oxidase 1. Rosiglitazone elevated plasma adiponectin level and normalized peroxisomal fatty acid β-oxidation rate. However, rosiglitazone did not affect ethanol-reduced very low-density lipoprotein secretion from the liver. These results demonstrated that activation of PPAR-γ by rosiglitazone reverses ethanol-induced adipose dysfunction and lipid dyshomeostasis at the WAT-liver axis, thereby abrogating alcoholic fatty liver.

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“…While MCD diet alone preferentially causes bile duct injury and cholestasis, ethanol interferes with protective antioxidative pathways, and subsequently combination of MCD diet and ethanol aggerates liver injury [88]. In humans chronic alcohol abuse is even associated with higher circulating levels of the hepatoprotective adipokine adiponectin which is significantly reduced in obesity and NAFLD [25,89]. Moderate alcohol intake has been shown to exert protective effects by increasing systemic high density lipoprotein thereby lowering inflammation and stimulating reverse cholesterol transport.…”

Section: Alcohol and Alcohol Metabolizing Enzymesmentioning

confidence: 98%

Does Hepatic Steatosis Affect Drug Metabolizing Enzymes in the Liver?

Buechler¹,

Weiss

2011

CDM

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Bioavailability and effects of xenobiotics are dependent on absorption, metabolism and elimination of the respective compounds. Hepatocytes are critically important in drug modification and excretion. Molecules like organic anion transporters mediate hepatocyte uptake of xenobiotics, which are subsequently modified by phase I enzymes with cytochrome (CYP) P450 isoenzymes like CYP3A4 being the most important. Phase II enzymes including glucuronosyltransferases further increase aqueous solubility of the respective compounds. The canalicular transport of these substances into the bile is mainly arranged by ATP-binding cassette transporters. Variations in the activity of these enzymes and transporters explain altered drug activity, elimination and eventually increased half-life and toxicity of xenobiotics. Body composition affects distribution of several drugs and fat mass may have to be taken into account in determining appropriate doses of lipophilic compounds. Adiposity is increasingly prevalent in western countries and about half of the adult population is overweight or even obese. Obesity is often associated with an enhanced storage of fat in hepatocytes and hepatic steatosis is diagnosed in nearly 30% of adults. Although this is a benign condition fatty liver is more susceptible to insults leading to non-alcoholic steatohepatitis (NASH) associated with inflammation and liver fibrosis. There is increasing evidence that drug metabolizing enzymes/transporters are differentially expressed in hepatic steatosis and NASH. Studies in animals, humans and in-vitro models suggesting altered expression of transcription factors, transporters and enzymes involved in drug metabolism in non-alcoholic fatty liver disease are summarized in the current review.

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Elevated adiponectin serum levels in patients with chronic alcohol abuse rapidly decline during alcohol withdrawal

Cited by 37 publications

References 31 publications

Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families

Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families

Activation of peroxisome proliferator-activated receptor-γ by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice

Does Hepatic Steatosis Affect Drug Metabolizing Enzymes in the Liver?

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