Taurine supplementation prevents ethanol‐induced decrease in serum adiponectin and reduces hepatic steatosis in rats

Adiponectin, an adipokine primarily secreted by adipose tissue, comprises about 0.01% of total serum protein (1). It circulates in three oligomeric forms: high molecular weight (HMW), middle molecular weight (MMW) and low molecular weight (LMW). Adiponectin interacts with two receptors, AdipoR1 and AdipoR2, which are expressed at high levels in skeletal muscle and liver, respectively (1). Adiponectin has important metabolic functions regulating both glucose and lipid homeostasis. Adiponectin stimulates fatty acid oxidation and decreases triglyceride accumulation in both liver and skeletal muscle (1). Serum adiponectin concentrations are decreased in both human and murine models of obesity, insulin resistance and type 2 diabetes (2;3). Adiponectin also has potent anti-inflammatory functions, acting to decrease the production of inflammatory cytokines, such as TNF-α and IL-6, by macrophages and adipocytes (1;4). Chronic alcohol consumption results in the development of alcoholic liver disease, characterized by the development of hepatic steatosis and an increase in the expression of a number of inflammatory mediators, including cytokines, reactive oxygen species and nitrogen species (5). Recent studies have implicated ethanol-induced changes in the expression of adipokines in mediating the pathophysiological effects of ethanol in the liver. Chronic ethanol exposure decreases serum adiponectin concentration in mice (6–8) and rats (9;10). Ethanol-induced decreases in circulating adiponectin are associated with lower adiponectin mRNA in subcutaneous adipose tissue, as well as a reduced rates of adiponectin secretion by subcutaneous adipocytes (10). Importantly, treatment of mice with adiponectin during chronic ethanol exposure prevents the development of ethanol-induced liver injury (7), in part by increasing fatty acid oxidation in the liver, thus preventing ethanol-induced steatosis, as well as decreasing TNF-α expression (7). While the mechanisms by which ethanol feeding decreases adiponectin expression and secretion are not well understood, a growing body of evidence indicates that adipose tissue is an important target for ethanol action. For example, chronic ethanol impairs insulin-stimulated glucose uptake (11) and disrupts the hormonal regulation of lipolysis (12). Chronic ethanol increases macrophage infiltration and inflammatory cytokine expression (13) and causes endoplasmic reticulum (ER) stress in adipose tissue (8). These changes in adipose tissue in response to chronic ethanol are similar to the increased numbers of infiltrating macrophages, increased proinflammatory cytokine expression (14;15), as well as ER stress (16), observed in adipose tissue in models of obesity and insulin resistance. “Chemical chaperones” is a term given to a group of low molecular weight osmolytes which stabilize protein conformation, thus improving the folding of proteins within the ER (17). Treatment of ob/ob mice with chemical chaperones, such as taurodeoxycholate, reduced ER stress in the liver and restored normal glucose homeostasis (18). Given the parallels between the impact of obesity-induced insulin resistance and chronic ethanol exposure on adipose tissue, both resulting in decreased adiponectin expression, as well as the development of ER stress and inflammation, here we have tested the ability of taurine, an endogenous sulfur containing amino acid that functions both as a chemical chaperone/osmolyte and enhances cellular anti-oxidant activity (19;20), to prevent the effects of ethanol on adipose tissue in rats. Here we report that chronic ethanol feeding for 1 week depleted taurine from subcutaneous adipose tissue, increased inflammatory cytokine expression and decreased adiponectin expression. Supplementation with taurine restored the concentration of taurine in adipose tissue and normalized cytokine and adiponectin expression. Importantly, taurine supplementation to rats also attenuated ethanol-induced steatosis, oxidative stress and TNF-α expression in the liver. These data indicate that the development of therapeutic interventions targeting the effects of ethanol on adipose tissue may be efficacious in the prevention of ethanol-induced liver injury.