Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats

Shklyaev, Stanislav; Aslanidi, George; Tennant, M; Prima, Victor; Kohlbrenner, Eric; Kroutov, Vadim; Campbell-Thompson, Martha; Crawford, James M.; Shek, Eugene W.; Scarpace, Philip J.; Zolotukhin, Sergei

doi:10.1073/pnas.2333912100

Cited by 228 publications

(188 citation statements)

References 57 publications

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“…Stimulation of fatty acid oxidation by adiponectin occurs through activation of AMPK, diminished ACC activity, and reduction of malonyl CoA content in the liver. [16][17][18] The phosphorylation of Thr172 in the ␣ subunit of AMPK is essential for AMPK activity, and the phosphorylation of ACC at Ser79 by AMPK is associated with reduced activity. 12 To determine whether the changes in serum adiponectin concentrations resulted in altered activities of AMPK and ACC in the livers of ethanol-fed mice, the phosphorylation states of AMPK-␣ and ACC were analyzed.…”

Section: A Hsf Diet Attenuated Hepatic Steatosis and Reversed Alaninementioning

confidence: 99%

“…[12][13][14][15] These molecules are the major mediators of the metabolic effect of adiponectin. 16,17 Adiponectin is exclusively expressed and secreted from adipose tissue. Circulating adiponectin concentrations account for approximately 0.01% of total plasma protein.…”

mentioning

confidence: 99%

“…16 AdipoR2 is predominantly expressed in the liver, where it mainly serves as the transducer of adiponectin-mediated activation of AMPK and PPAR-␣, leading to increased fatty acid oxidation and reduced fat accumulation. 16,17 Altered expression of adiponectin may be associated with alcohol-induced liver injury. Chronic ethanol consumption significantly decreased circulating concentrations of adiponectin in mice.…”

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confidence: 99%

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Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice

et al. 2005

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The protective effect of dietary saturated fatty acids against the development of alcoholic liver disease has long been known, but the underlying mechanism is not completely understood. We examined the involvement of the adipocyte hormone adiponectin. Circulating adiponectin levels were significantly elevated by chronic ethanol administration to mice consuming a diet high in saturated fat. The increase in circulating adiponectin was associated with the activation a set of hepatic signaling pathways mediated through AMP-activated protein kinase, PPAR-␣, and PPAR-␥ coactivator ␣, which in turn led to markedly increased rates of fatty acid oxidation, prevention of hepatic steatosis, and alleviation of liver enzyme changes. Furthermore, treatment of rat 3T3-L1 adipocytes with saturated fatty acids (palmitic or stearic acids) in the presence of ethanol increased secretion of adiponectin and enhanced activity of a mouse adiponectin promoter. In conclusion, the protective action of saturated fat against the development of alcoholic fatty liver in mice is partially mediated through induction of adiponectin. The present findings suggest a novel paradigm for dietary fatty acids in the pathogenesis of alcoholic liver disease and provide a promising therapeutic strategy-nutritional modulation of adiponectin-in treating human alcoholic fatty liver disease. (HEPATOLOGY 2005;42:568 -577.)

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Section: A Hsf Diet Attenuated Hepatic Steatosis and Reversed Alaninementioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice

et al. 2005

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“…Peripheral adiponectin treatment decreases body fat by enhancing energy expenditure and fatty acid oxidation (76). Chronic adiponectin treatment reduces food intake, weight, glucose, and lipids in obese rats (77). Moreover, adiponectin and leptin are inversely related to seasonal changes in WAT mass and adipocyte lipid content in mammalian hibernators (78).…”

Section: Role Of Leptin In Famine and Feastmentioning

confidence: 99%

Brain Adipocytokine Action and Metabolic Regulation

et al. 2006

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Adipose tissue secretes factors that control various physiological systems. The fall in leptin during fasting mediates hyperphagia and suppresses thermogenesis, thyroid and reproductive hormones, and immune system. On the other hand, rising leptin levels in the fed state stimulate fatty acid oxidation, decrease appetite, and limit weight gain. These divergent effects of leptin occur through neuronal circuits in the hypothalamus and other brain areas. Leptin also regulates the activities of enzymes involved in lipid metabolism, e.g., AMP-activated protein kinase and stearoyl-CoA desaturase-1, and also interacts with insulin signaling in the brain. Adiponectin enhances fatty acid oxidation and insulin sensitivity, in part by stimulating AMP-activated protein kinase phosphorylation and activity in liver and muscle. Moreover, adiponectin decreases body fat by increasing energy expenditure and lipid catabolism. These effects involve peripheral and possibly central mechanisms. Adipose tissue mediates interconversion of steroid hormones and secretes proinflammatory cytokines, vasoactive peptides, and coagulation and complement proteins. Understanding the actions of these "adipocytokines" will provide insight into the pathogenesis and treatment of obesity and related diseases. Diabetes 55 (Suppl. 2): S145-S154, 2006 ADIPOSE TISSUE

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“…Several studies demonstrate that reduced SREBP-1 mRNA and protein expression in rat hepatocytes and liver result from AMPK activation. Activation of AMPK decreased the stability of mature SREBP-1 protein in hepatocytes by acceleration of its proteasomal degradation (25,16). Therefore, we tested the hypothesis that AMPK may play a role in mediating the effects of ethanol on SREBP-1.…”

Section: Involvement Of Ampk In Ethanol Effectsmentioning

confidence: 99%

Recent Advances in Alcoholic Liver Disease II. Minireview: molecular mechanisms of alcoholic fatty liver

You

Crabb

2004

American Journal of Physiology-Gastrointestinal and Liver Physi

199

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Alcohol has long been thought to cause fatty liver by way of altered NADH/NAD+ redox potential in the liver, which, in turn, inhibits fatty acid oxidation and the activity of tricarboxylic acid cycle reactions. More recent studies indicate that additional effects of ethanol both impair fat oxidation and stimulate lipogenesis. Ethanol interferes with DNA binding and transcription-activating properties of peroxisome proliferator-activated receptor-α (PPARα), as demonstrated with cultured cells and in ethanol-fed mice. Treatment of ethanol-fed mice with a PPARα agonist can reverse fatty liver even in the face of continued ethanol consumption. Ethanol also activated sterol regulatory element binding protein 1, inducing a battery of lipogenic enzymes. These effects may be due in part to inhibition of AMP-dependent protein kinase, reduction in plasma adiponectin, or increased levels of TNF-α in the liver. The understanding of these ethanol effects provides new therapeutic targets to reverse alcoholic fatty liver.

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Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats

Cited by 228 publications

References 57 publications

Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice

Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice

Brain Adipocytokine Action and Metabolic Regulation

Recent Advances in Alcoholic Liver Disease II. Minireview: molecular mechanisms of alcoholic fatty liver

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