title: Long-term moderate ethanol consumption restores insulin sensitivity in high-fat-fed rats by increasing SLC2A4 (GLUT4) in the adipose tissue by AMP-activated protein kinase activation.
abstract: The sole effect of either saturated fatty acid or moderate ethanol consumption on SLC2A4 (GLUT4) expression is widely reported but the combined effects of them remain obscure. Here, we observed their combined effects on SLC2A4 expression, explored the underlying mechanism mediated by AMP-activated protein kinase alpha (PRKAA2) and myocyte enhancer factor 2 (MEF2) both in vivo and in vitro. In the in vivo experiments, 36 male Wistar rats, divided into three groups, were fed with normal diet, high-fat (HF) diet, or HF diet plus ethanol for 22 weeks. We measured the expressions of total-PRKAA2 (T-PRKAA2), phosphorylated-PRKAA2 (pPRKAA2, activated form of PRKAA2), MEF2, and SLC2A4 in epididymal adipose tissues. In the in vitro experiments, primary adipocytes, isolated from normal Wistar rats, were incubated in the presence or absence of palmitate, ethanol, and compound C (an PRKAA2 inhibitor) for 1 h. Thereafter, T-PRKAA2, pPRKAA2, MEF2, and SLC2A4 expressions were measured. We found that both HF diet and in vitro exposition to palmitate impaired SLC2A4 expression in rat adipocytes with a parallel reduction in PRKAA2 activation and MEF2 expression. This impairment was reversed by ethanol administration. We further demonstrated that ethanol-mediated PRKAA2 activation stimulates MEF2 and SLC2A4 expressions in adipocytes, as evidenced by compound C blockade of these effects. In summary, long-term moderate ethanol consumption reversed the adverse effect of saturated fatty acid on SLC2A4 expression in adipocytes, which was likely to be a result of PRKAA2 activation and subsequent up-regulation of MEF2 and SLC2A4 expressions.
authors: Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, People's Republic of China.
authors: Li
authors: L
authors: Feng
authors: Ling
authors: L
authors: Gao
authors: Qingbo
authors: Q
authors: Guan
authors: Xiaolei
authors: X
authors: Hou
authors: Qiang
authors: Q
authors: Wan
authors: Xiangdong
authors: X
authors: Wang
authors: Jiajun
authors: J
authors: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004041:Dietary Fats / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D018149:Glucose Intolerance / Q000139:chemically induced / Q000517:prevention & control*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D008297:Male; D018006:Myogenic Regulatory Factors / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D052242:Adiponectin; D004041:Dietary Fats; D051275:Glucose Transporter Type 4; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D018006:Myogenic Regulatory Factors; C495693:Slc2a4 protein, mouse; D000431:Ethanol; D055372:AMP-Activated Protein Kinases