title: Upregulation of Pnpla2 and Abhd5 and downregulation of G0s2 gene expression in mesenteric white adipose tissue as a potential reason for elevated concentration of circulating NEFA after removal of retroperitoneal, epididymal, and inguinal adipose tissue.
abstract: Elevated concentrations of circulating non-esterified fatty acids (NEFA) were reported in (a) humans with lipodystrophy, (b) humans following bariatric surgery, and (c) transgenic mice with reduced amounts of adipose tissue. Paradoxically, these findings suggest that the reduction of adipose tissue mass is associated with elevated circulating NEFA concentrations. To explain a molecular background of this phenomenon, we analyzed the effects of surgical removal of inguinal, epididymal, and retroperitoneal white adipose tissue (WAT) on (a) circulating NEFA concentrations, (b) expression of Pnpla2, a gene that encodes adipose triglyceride lipase (ATGL), genes encoding abhydrolase domain containing 5 (ABHD5) and G0/G1 switch 2 (G0S2), i.e., a coactivator and inhibitor of ATGL, respectively, and (c) expression of Lipe gene coding hormone-sensitive lipase (HSL) in mesenteric WAT. Reduction of adipose tissue mass resulted in an increase in circulating NEFA concentration, which was associated with (a) an increase in the expressions of Pnpla2 and Abhd5, (b) decrease in G0s2 expression, and (c) upregulation of Lipe expression, all measured on both mRNA and protein levels in mesenteric WAT of male rats. The rate of lipolysis in mesenteric WAT explants and isolated adipocytes from lipectomized rats was significantly higher than that from the controls. In conclusion, upregulation of Pnpla2 expression and activation of ATGL (due to an increase in ABHD5 and decrease in G0S2 levels), as well as a coordinated interplay of these genes with Lipe in mesenteric WAT, contribute, at least in part, to an increase in the concentration of circulating NEFA in rats with reduced fat mass.
authors: Department of Biochemistry, Medical University of Gdansk, Dębinki 1, 80-211, Gdansk, Poland.
authors: Agnieszka
authors: A
authors: Dettlaff-Pokora
authors: Department of Pharmaceutical Biochemistry, Medical University of Gdansk, Dębinki 1, 80-211, Gdansk, Poland.
authors: Tomasz
authors: T
authors: Sledzinski
authors: Department of Biochemistry, Medical University of Gdansk, Dębinki 1, 80-211, Gdansk, Poland. juls@gumed.edu.pl.
authors: Julian
authors: J
authors: Swierczynski
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004822:Epididymis / Q000378:metabolism / Q000601:surgery; D008049:Lipase / Q000378:metabolism*; D008297:Male; D008643:Mesentery / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000080866:Nucleobindins; D051381:Rats; D017208:Rats, Wistar
chemical_list: C520594:Abhd5 protein, rat; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C586945:G0S2 protein, rat; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D000217:Acyltransferases; D008049:Lipase; C571275:PNPLA2 protein, rat
keywords: ABHD5; ATGL; Adipose tissue; G0S2; HSL; Lipolysis; NEFA