Chronic AICAR-induced AMP-kinase activation regulates adipocyte lipolysis in a time-dependent and fat depot-specific manner in rats.
This study investigated the effects of chronic in vivo AMP-kinase activation with 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) on lipolysis in subcutaneous inguinal, epididymal, and retroperitoneal fat pads. Male Wistar rats received daily single intraperitoneal injections of either saline or AICAR (0.7 g/kg body wt) for a period of 8 wk. The fat pads were used either to isolate adipocytes and measure basal and catecholamine-stimulated lipolysis or to assess signaling steps of lipolysis after 4 and 8 wk of AICAR treatment. Blood was sampled weekly to measure nonesterified fatty acids (NEFAs). AICAR treatment reduced basal and catecholamine-stimulated lipolysis at week 4 in adipocytes from all fat depots. However, at week 8, catecholamine-induced lipolysis significantly increased in inguinal and retroperitoneal adipocytes. Interestingly, plasma levels of NEFAs were also decreased and subsequently increased at 4 and 8 wk, respectively. The lipolytic cascade of the inguinal fat pad was the most drastically affected by the treatment, since the phosphorylation and content of most proteins involved in lipolysis were consistently undetected in this tissue after 4 and 8 wk of AICAR treatment. The enhancement of catecholamine-induced lipolysis in inguinal and retroperitoneal adipocytes after 8 wk of AICAR treatment was accompanied by increased contents of adipose triglyceride lipase (ATGL) and perilipin A in these fat depots. In summary, despite depot-specific regulation of the lipolytic cascade, catecholamine-induced lipolysis in isolated adipocytes correlated well with plasma NEFA concentrations in the course of chronic AICAR-induced AMPK activation. The mechanisms underlying these effects also involved time-dependent and depot-specific regulation of hormone-sensitive lipase, ATGL, and perilipin.
Muscle Health Research Center–School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
Mandeep P
MP
Gaidhu
George
G
Bikopoulos
Rolando B
RB
Ceddia
D000263:Adenylate Kinase / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology; D000273:Adipose Tissue / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D002395:Catecholamines / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008049:Lipase / Q000032:analysis; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000008:administration & dosage*; D000217:Acyltransferases
D000263:Adenylate Kinase; D000620:Aminoimidazole Carboxamide; D002352:Carrier Proteins; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D008049:Lipase; D000070778:Perilipin-1; D010750:Phosphoproteins; D012265:Ribonucleotides; C571275:PNPLA2 protein, rat; D000217:Acyltransferases; C031143:AICA ribonucleotide