Chronic ethanol and triglyceride turnover in white adipose tissue in rats - Inhibition of the anti-lipolytic action of insulin after chronic ethanol contributes to increased triglyceride degradation

Department of Mathematics, Case Western Reserve University, Cleveland, Ohio, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 10/2007; 282(39):28465-73. DOI: 10.1074/jbc.M705503200
Source: PubMed


Chronic ethanol consumption disrupts whole-body lipid metabolism. Here we tested the hypothesis that regulation of triglyceride homeostasis in adipose tissue is vulnerable to long-term ethanol exposure. After chronic ethanol feeding, total body fat content as well as the quantity of epididymal adipose tissue of male Wistar rats was decreased compared with pair-fed controls. Integrated rates of in vivo triglyceride turnover in epididymal adipose tissue were measured using (2)H(2)O as a tracer. Triglyceride turnover in adipose tissue was increased due to a 2.3-fold increase in triglyceride degradation in ethanol-fed rats compared with pair-fed controls with no effect of ethanol on triglyceride synthesis. Because increased lipolysis accompanied by the release of free fatty acids into the circulation is associated with insulin resistance and liver injury, we focused on determining the mechanisms for increased lipolysis in adipose tissue after chronic ethanol feeding. Chronic ethanol feeding suppressed beta-adrenergic receptor-stimulated lipolysis in both in vivo and ex vivo assays; thus, enhanced triglyceride degradation during ethanol feeding was not due to increased beta-adrenergic-mediated lipolysis. Instead, chronic ethanol feeding markedly impaired insulin-mediated suppression of lipolysis in conscious rats during a hyperinsulinemic-euglycemic clamp as well as in adipocytes isolated from epididymal and subcutaneous adipose tissue. These data demonstrate for the first time that chronic ethanol feeding increased the rate of triglyceride degradation in adipose tissue. Furthermore, this enhanced rate of lipolysis was due to a suppression of the anti-lipolytic effects of insulin in adipocytes after chronic ethanol feeding.

  • Source
    • "Another mechanism which may contribute to postprandial HT is a decrease of lipogenesis and glucose oxidation in adipose tissue, as shown in rats after chronic ethanol feeding [10]. Kang et al. [11] studied triglyceride turnover in white adipose tissue and showed that chronic alcohol consumption inhibits the antilipolytic action of insulin. It has also been shown that the lipemic response to alcohol is related to the stage of liver disease, since in cirrhosis, in contrast to steatosis, fasting lipid response is neglectable, but postmeal chylomicron response is increased [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alcohol has a significant additive effect on the postprandial triglyceride peak when it accompanies a meal containing fat, especially saturated fat. This results from a decrease in the breakdown of chylomicrons and VLDL remnants due to an acute inhibitory effect of alcohol on lipoprotein lipase activity. Furthermore, alcohol increases the synthesis of large VLDL particles in the liver, which is the main source of triglycerides in the hypertriglyceridemia associated with chronic excessive alcohol intake. In case of chronic consumption, lipoprotein lipase activity seems to adapt itself. The effect of alcohol on adipose tissues is less clear. Sometimes, a severe hypertriglyceridemia induced by alcohol (SHIBA) can be observed, especially in patients with type 2 diabetes mellitus and/or obesity increasing the risk of pancreatitis.
    Full-text · Article · Jan 2012 · International journal of vascular medicine
  • Source
    • "At present, ethanol is the most widely abused addictive substance. In addition to decreasing glucose uptake in rat adipocytes10, chronic ethanol exposure in rats has been shown to increase the rate of triglyceride degradation in adipose tissue, resulting in elevated circulating free fatty acids (FFAs)11. Our prior results measured depressed insulin-stimulated glucose uptake and increased insulin resistance in isolated skeletal muscle of rats exposed to chronic excess ethanol12. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the effects of ethanol on adipokines (leptin, adiponectin, resistin, visfatin and cartonectin) levels in visceral adipose tissue (VAT) and sera, and explore the correlation between VAT and serum adipokine levels. Forty-eight Wistar rats were randomly divided into control, low, middle and high ethanol treatment groups that received 0, 0.5, 2.5, or 5.0 g of ethanol x kg(-1) x d(-1), respectively, via gastric tubes for 22 weeks. The levels of fasting blood glucose (FBG) and fasting serum insulin (FINS) were measured and homeostasis model assessment of insulin resistance (HOMA-IR) values were calculated. Adipokines in perirenal and epididymal VAT and sera were measured by enzyme-linked immunosorbent assays (ELISAs). High-dose treatments of ethanol (vs control group) significantly increased FINS (eg 37.86%) and HOMA-IR values (eg 40.63%). In VAT, levels of leptin, resistin and visfatin in the middle- and high-dose groups were significantly elevated, whereas adiponectin and cartonectin levels decreased. In sera, changes in adipokine levels were similar to that observed in VAT, with the exception of cartonectin. These ethanol-induced effects were dose-dependent. A positive correlation existed between VAT and serum adipokine levels, except for cartonectin. Chronic ethanol consumption affects adipokine levels in VAT and sera in a dose-dependent manner, with the exception of serum cartonectin. The altered levels of adipokines in VAT and sera are positively correlated.
    Full-text · Article · Mar 2010 · Acta Pharmacologica Sinica
  • Source
    • "Besides the major pathways indicated in this diagram, ethanol intake is also known to promote fat transport into the liver from peripheral tissues (e.g. adipose tissues) while ethanol inhibits fat export from the liver (Baraona and Lieber, 1979;Kang et al., 2007a;Lieber, 2004). Because of common features of fat accumulation and disease progression (Diehl et al., 1988;Wilfred de Alwis and Day, 2007), it is expected that similar mechanisms of the major pathways for alcoholic fatty liver (Fig. 1) could also exist in animal models and human patients suffering from nonalcoholic steatohepatitis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. Alcohol exposure may induce fatty liver by increasing NADH/NAD(+) ratio, increasing sterol regulatory element-binding protein-1 (SREBP-1) activity, decreasing peroxisome proliferator-activated receptor-alpha (PPAR-alpha) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP-1 activity by decreasing the activities of AMP-activated protein kinase and sirtuin-1. Tumor necrosis factor-alpha (TNF-alpha) produced in response to alcohol exposure may cause fatty liver by up-regulating SREBP-1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down-regulating SREBP-1 activity. PPAR-alpha agonists have potentials to attenuate alcoholic fatty liver. Adiponectin and interleukin-6 may attenuate alcoholic fatty liver by up-regulating PPAR-alpha and insulin signaling pathways while down-regulating SREBP-1 activity and suppressing TNF-alpha production. Recent studies show that paracrine activation of hepatic cannabinoid receptor 1 by hepatic stellate cell-derived endocannabinoids also contributes to the development of alcoholic fatty liver. Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal beta-oxidation of fatty acids could contribute to fat accumulation in the liver.
    Preview · Article · Dec 2008 · Alcoholism Clinical and Experimental Research
Show more