Chronic TNFα and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis

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.

Abbreviations: 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

Keywords: Hormone-sensitive lipase, Adipose triglyceride lipase, Lipolysis, TNFα, Forskolin, Protein kinase A