Notably it is also reported that changes in lipoprotein
Notably, it is also reported that changes in lipoprotein lipase (LPL) activity, HSL activity, and cAMP accumulation in WAT and BAT after ethanol exposure differ depending on the dose and route of ethanol exposure and tissue type. Moreover, a recent study also found that chronic feeding plus alcohol binging in mice increased adipose intracellular cAMP levels, resulting in the activation of lipolytic neuron specific enolase and increased lipolysis. This effect was reversed by recombinant human fibroblast growth factor 21 (FGF21) treatment. Therefore, it appears that the ethanol treatment conditions may affect how ethanol induces adipocyte lipolysis. While the mechanisms for ethanol-induced adipocyte lipolysis remain controversial, it is clear that alcohol consumption can lead to adipose tissue atrophy.
Effects of alcohol on protein metabolism and autophagy activity In addition to the known catecholamine and beta-adrenergic receptor-mediated lipolysis and insulin-mediated anti-lipolysis signaling in alcohol-induced adipocyte lipolysis, several other mechanisms are emerging that may also contribute to alcohol-induced adipose tissue homeostasis and lipolysis. Chronic alcohol consumption is known to cause mass loss and dysregulated protein metabolism in skeletal muscle. Investigators determined that the mechanisms include inhibited global protein synthesis and increased autophagy degradation. Surprisingly, a recent study demonstrated that mice with chronic ethanol consumption for 24 weeks displayed increased protein synthesis, which was associated with increased mTOR substrate protein phosphorylation and Atg gene expression. It is likely that increased mTOR-mediated protein synthesis may reflect an adaptive response by adipose tissue to alcohol-induced adipose tissue atrophy. While the authors observed increased Atg gene expression following alcohol exposure, autophagy flux assays were not performed in this study. It thus remains unclear whether autophagy is increased in adipocytes in this model. As discussed above, adipocyte-specific Atg5 or Atg7 knockout mice display decreased adipose tissue mass, which is similar to chronic alcohol-induced adipose tissue atrophy. One would assume that chronic alcohol intake may also impair autophagy in adipocytes. Determining autophagic flux in vivo, such as in mouse adipose tissue, is technically challenging. Thus, better animal models and autophagic flux markers need to be developed to further tackle this important question in the future.
Adipose tissue-liver axis in ALD Adipose tissue is an endocrine organ that secretes many bioactive substances, collectively called adipokines. To date, more than 600 adipokines have been found to play specific roles in the immune response, inflammation, glucose/lipid metabolism, insulin sensitivity, regulation of appetite and satiety, adipogenesis and bone morphogenesis, and other biological processes. Excess adiposity or adipocyte dysfunction leads to dysregulation of adipokines and nutritional metabolites and thus affects other organs, such as the liver and skeletal muscle. Correspondingly, disorders in the liver and skeletal muscle can also affect adipose tissue mass and function. Emerging evidence has revealed that adiponectin and FGF21 are two potential key mediators of the crosstalk between adipose tissue and liver. Adiponectin or 30 kDa adipocyte complement-related protein, encoded by Adipoq, is a protein hormone predominantly expressed in adipose tissue. Serving as an anti-diabetic adipocytokine, it regulates glucose levels and FA breakdown. Metabolically, it reduces body fat and improves insulin sensitivity. Moreover, adiponectin has anti-inflammatory effects, such as blocking macrophage function and nuclear factor-kappaB (NF-κB) signaling. Different forms of adiponectin supplementation have been shown to treat obesity, diabetes, and insulin resistance. Adiponectin has two receptors, AdipoR1 and AdipoR2, and the latter is highly expressed in the liver. Adiponectin is able to regulate liver steatosis, insulin resistance, inflammation, and fibrosis, all of which are important for ALD pathogenesis, by binding to these two receptors. Indeed, chronic alcohol intake decreases circulating adiponectin levels in mice and rats, and supplementation of recombinant adiponectin alleviates alcohol-induced liver steatosis and injury. These data clearly support the notion that modulating adipose tissue function can affect ALD pathogenesis.