Omega-3 polyunsaturated fatty acids ameliorate ethanol-induced adipose hyperlipolysis: A mechanism for hepatoprotective effect against alcoholic liver disease

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2017-12, Vol.1863 (12), p.3190-3201
• Main Authors: Wang, Meng, Zhang, Xiaojiao, Ma, Li-Juan, Feng, Rui-Bing, Yan, Chunyan, Su, Huanxing, He, Chengwei, Kang, Jing X., Liu, Baolin, Wan, Jian-Bo
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes - drug effects; Adipocytes - metabolism; Adipocytes - pathology; Adipose lipolysis; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adiposity - drug effects; Alcoholic liver disease; Animals; Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism; CaMKKβ; Cyclic AMP - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism; Docosahexaenoic Acids - pharmacology; Eicosapentaenoic Acid - pharmacology; Ethanol - pharmacology; Fatty Acids, Omega-3 - pharmacology; Fatty Liver, Alcoholic - prevention & control; Female; GPR120; Lipolysis - drug effects; Liver Diseases, Alcoholic - metabolism; Liver Diseases, Alcoholic - prevention & control; Mice; Mice, Inbred C57BL; Mice, Transgenic; Omega-3 polyunsaturated fatty acids; Protective Agents - pharmacology; Protein Kinases - metabolism; Receptors, G-Protein-Coupled - metabolism; Signal Transduction
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2017.08.026

Alcohol exposure induces adipose hyperlipolysis and causes excess fatty acid influx into the liver, leading to alcoholic steatosis. The impacts of omega-3 polyunsaturated fatty acids (n-3 PUFA) on ethanol-induced fatty liver are well documented. However, the role of n-3 PUFA in ethanol-induced adipose lipolysis has not been sufficiently addressed. In this study, the fat-1 transgenic mice that synthesizes endogenous n-3 from n-6 PUFA and their wild type littermates with an exogenous n-3 PUFA enriched diet were subjected to a chronic ethanol feeding plus a single binge as model to induce liver injury with adipose lipolysis. Additionally, the differentiated adipocytes from 3T3-L1 cells were treated with docosahexaenoic acid or eicosapentaenoic acid for mechanism studies. Our results demonstrated that endogenous and exogenous n-3 PUFA enrichment ameliorates ethanol-stimulated adipose lipolysis by increasing PDE3B activity and reducing cAMP accumulation in adipocyte, which was associated with activation of GPR120 and regulation of Ca2+/CaMKKβ/AMPK signaling, resultantly blocking fatty acid trafficking from adipose tissue to the liver, which contributing to ameliorating ethanol-induced adipose dysfunction and liver injury. Our findings identify that endogenous and exogenous n-3 PUFA enrichment ameliorated alcoholic liver injury by activation of GPR120 to suppress ethanol-stimulated adipose lipolysis, which provides the new insight to the hepatoprotective effect of n-3 PUFA against alcoholic liver disease. [Display omitted] •N-3 PUFA enrichment ameliorates ethanol-stimulated adipose lipolysis.•The anti-lipolysis effect of n-3 PUFA is associated with activation of GPR120.•The activation of GPR120 regulated Ca2+/CaMKKβ/AMPK/PDE3B/cAMP signaling.•The anti-lipolysis effect of n-3 PUFA alleviated ethanol-induced liver injury.