Infusion of a lipid emulsion modulates AMPK and related proteins in rat liver, muscle, and adipose tissues.
The primary objective of this study was to investigate the impact of lipid oversupply on the AMPK pathway in skeletal muscle, liver, and adipose tissue. Male Wistar rats were infused with lipid emulsion (LE) or phosphate-buffered saline for 5 h/day for 6 days. Muscles exposed to LE for 6 days exhibited increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, along with a greater association between AMPK and Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK). No differences in muscle protein phosphatase 2C (PP2C) activity, LKB1 phosphorylation or AMPK and LKB1 association were observed. Muscle ACCbeta, and adiponectin receptor 1 (AdipoR1) mRNA levels and PPARgamma-co-activator 1alpha (PGC1alpha) protein levels were also increased in LE-treated rats. In contrast, AMPK and ACC phosphorylation decreased and PP2C activity increased in rat livers exposed to LE. Hepatic mRNA levels of ACCalpha, PPARalpha, AdipoR1, AdipoR2, and sterol regulatory element-binding protein-1c (SREBP1c) were also reduced after LE infusion. In adipose tissue, there was no significant alteration in AMPK or ACC phosphorylation. These results demonstrate that following lipid oversupply the AMPK pathway was enhanced in rat skeletal muscle while diminished in the liver and was unchanged in adipose tissue. CaMKK in skeletal muscle and PP2C in the liver, at least in part, appear to mediate these alterations. Alterations in AMPK pathway in the liver induced metabolic defects associated with lipid oversupply.
Anavi
Sarit
S
The Hebrew University of Jerusalem, Faculty of Agricultural, Food and Environmental Quality Sciences, Institute of Biochemistry, Food Science and Nutrition, Rehovot, Israel.
Ilan
Erez
E
Tirosh
Oren
O
Madar
Zecharia
Z
D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007262:Infusions, Intravenous; D007333:Insulin Resistance / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D000071636:Protein Phosphatase 2C; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D052242:Adiponectin; D005217:Fat Emulsions, Intravenous; D007527:Isoenzymes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D011506:Proteins; D016601:RNA-Binding Proteins; D054419:Receptors, Adiponectin; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; D000103:Acetyl-CoA Carboxylase