Abstract
The effect of hydrogen sulfide (H2S) on differentiation of 3T3L1-derived adipocytes was examined. Endogenous H2S was increased after 3T3L1 differentiation. The expression of the H2S-synthesising enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), was increased in a time-dependent manner during 3T3L1 differentiation. Expression of genes associated with adipogenesis related genes including fatty acid binding protein 4 (FABP4/aP2), a key regulator of this process, was increased by GYY4137 (a slow-releasing H2S donor compound) and sodium hydrosulfide (NaHS, a classical H2S donor) but not by ZYJ1122 or time-expired NaHS. Furthermore expression of these genes were reduced by aminooxyacetic acid (AOAA, CBS inhibitor), DL-propargylglycine (PAG, CSE inhibitor) as well as by CSE small interference RNA (siCSE) and siCBS. The size and number of lipid droplets in mature adipocytes was significantly increased by both GYY4137 and NaHS, which also impaired the ability of CL316,243 (β3-agonist) to promote lipolysis in these cells. In contrast, AOAA and PAG had the opposite effect. Taken together, we show that the H2S-synthesising enzymes CBS, CSE and 3-MST are endogenously expressed during adipogenesis and that both endogenous and exogenous H2S modulate adipogenesis and adipocyte maturation.
Highlights
Obesity, a major health issue in developed countries, is widely regarded as a chronic inflammatory state which contributes to numerous pathologies including dyslipidemia, coronary heart disease, non-alcoholic fatty liver, insulin resistance and type II diabetes [1,2,3,4]
Lipid accumulation in adipose tissue is tightly controlled by a range of adipogenesis-related molecules including fatty acids binding protein 4 (FABP4/aP2), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (CEBPα), sterol regulatory element binding protein-1 (SREBP1), carbohydrate responsive element binding protein (ChREBP), fatty acid synthase (FAS), hormone-sensitive lipase (HSL), perilipin A and a 47 kDa tail interacting protein
Goat anti-mouse FABP4/aP2 antibody was purchased from Santa Cruz Biotechnology (Santa Cruz, CA), rabbit anti-mouse CBS, β-actin and mouse anti-mouse cystathionine γ-lyase (CSE) were obtained from Abcam (Cambridge, MA), and rabbit anti-mouse 3-mercaptopyruvate sulfurtransferase (3-MST) was obtained from Sigma-Aldrich
Summary
A major health issue in developed countries, is widely regarded as a chronic inflammatory state which contributes to numerous pathologies including dyslipidemia, coronary heart disease, non-alcoholic fatty liver, insulin resistance and type II diabetes [1,2,3,4]. Obesity is associated with accumulation of excess triacylglyceride (TG) in adipocytes either due to innate hyperadipogenesis or to lipid overloading in adipose tissue [5,6,7]. Lipid accumulation in adipose tissue is tightly controlled by a range of adipogenesis-related molecules including fatty acids binding protein 4 (FABP4/aP2), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (CEBPα), sterol regulatory element binding protein-1 (SREBP1), carbohydrate responsive element binding protein (ChREBP), fatty acid synthase (FAS), hormone-sensitive lipase (HSL), perilipin A and a 47 kDa tail interacting protein. HSL, perilipin A and TIP47, enzymes which bind intracellular lipid droplets, serve to regulate TG breakdown and glycerol release from mature adipocytes [13,15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
