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Chronic TNFα and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis
Authors:Véronic Bézaire  Aline Mairal  Rodica Anesia  Corinne Lefort  Dominique Langin
Institution:a Laboratoire de Recherches sur les Obésités, Inserm U858, Toulouse, France
b Université de Toulouse, UPS, Institut de Médecine Moléculaire de Rangueil, IFR150, Toulouse, France
c CHU de Toulouse, Laboratoire de Biochimie, Institut Fédératif de Biologie de Purpan, Toulouse, France
Abstract:We examined the effects of chronic TNFα and dibutyryl-cAMP (Db-cAMP) pre-treatment on the lipolytic machinery of human hMADS adipocytes. TNFα decreased adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein content and triglycerides (TG)-hydrolase activity but increased basal lipolysis due to a marked reduction in perilipin (PLIN) protein content. Conversely, Db-cAMP increased ATGL and HSL protein content but prevented PLIN phosphorylation, the net result being accentuated basal lipolysis. In forskolin-stimulated conditions, TNFα and Db-cAMP pre-treatment decreased stimulated TG-hydrolase activity and impaired PLIN phosphorylation. Together, this resulted in a severely attenuated response to forskolin-stimulated lipolysis.
Keywords:ACS  acyl-CoA synthase  ATGL  adipose triglyceride lipase  Bay  4-isopropyl-3-methyl-2-[1-(3-(S)-methyl-piperidin-1-yl)-methanoyl]-2H-isoxazol-5-one  DG  diglycerides  Db-cAMP  dibutyryl-cyclic AMP  FK  forskolin  hMADS cells  human adipose tissue derived-multipotent stem cells  HSL  hormone-sensitive lipase  JNK  c-jun NH2 terminal kinase  LD  lipid droplet  MAPK  mitogen-activated protein kinase  NF-κB  nuclear factor κB  NPRA  natriuretic peptide receptor A  OA  oleic acid  PAT  Perilipin  adipophilin  TIP-47  PDE3B  phosphodiesterase 3B  PKA  protein kinase A  PLIN  perilipin  TG  triglycerides
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