Abstract
ObjectiveAdipose tissue expressed endogenous cystathionine gamma lyase (CSE)/hydrogen sulfide (H2S) system. H2S precursor inhibited catecholamine stimulated lipolysis. Thus, we hypothesized that CSE/H2S system regulates lipolysis which contributed to the pathogenesis of insulin resistance.MethodsWe treated rat adipocyte with DL-propargylglycine (PAG, a CSE inhibitor), L-cysteine (an H2S precursor) plus pyridoxial phosphate (co-enzyme) or the H2S chronic release donor GYY4137, then the glycerol level was assayed for assessing the lipolysis. Then, the effects of PAG and GYY4137 on insulin resistance in high fatty diet (HFD) induced obese mice were investigated.ResultsHere, we found that PAG time-dependently increased basal or isoproterenol stimulated lipolysis. However, L-cysteine plus pyridoxial phosphate or GYY4137 significantly reduced it. PAG increased phosphorylated protein kinase A substrate, perilipin 1 and hormone sensitive lipase, but L-cysteine and GYY4137 decreased the parameters. In HFD induced obese mice, PAG increased adipose basal lipolysis, thus blunted fat mass increase, resulting in lowering insulin resistance evidenced by reduction of fasting glucose, insulin level, HOMA index, oral glucose tolerance test (OGTT) curve area and elevating the insulin tolerance test (ITT) response. GYY4137 inhibited lipolysis in vivo without increasing fat mass, but also ameliorated the insulin resistance in HFD mice.ConclusionThese results implicated that inhibition endogenous CSE/H2S system in adipocytes increased lipolysis by a protein kinase A-perilipin/hormone-sensitive lipase pathway, thus blunted fat mass increase and reduced insulin resistance in obese mice; giving H2S donor decreased lipolysis, also reduced insulin resistance induced by HFD. Our data showed that increase or decrease H2S induced opposite lipolysis, but had the same effect on insulin resistance. The paradoxical regulation may be resulted from different action of H2S on metabolic and endocrine function in adipocyte.
Highlights
Obesity is popular diseases in developed and developing countries and major characteristic is fat mass increase
The excess free fatty acids (FFAs) from obese adipocyte induced target tissues local inflammatory response, oxidative stress, endoplasmic reticulum stress and metabolic disorder etc. which seem to be metabolic risk factors contributing to the pathogenesis of diabetes and insulin resistance [2]
To confirm the effect in vivo, we evaluated the effects of PAG and GYY4137 on lipolysis and insulin resistance in obesity mice induced by high fatty diet (HFD)
Summary
Obesity is popular diseases in developed and developing countries and major characteristic is fat mass increase. All mammals store excess amounts of energy in the form of intracellular triglycerides, mainly in lipid droplets. Starvation or stress-stimulated lipolysis reduced, but basal triglyceride lipolysis elevated released more free fatty acids (FFAs) into the bloodstream. Three major lipases control lipolysis: adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoglyceride lipase [3]. HSL is a well-known rate-limiting enzyme of lipolysis under starvation and stress [1]; PKA phosphorylated HSL at Ser659, and Ser660 site increased [6], and AMP-activated protein kinase (AMPK) phosphorylated HSL at Ser565 [7] inhibited HSL activity. Phosphorylation perilipin by PKA results in perilipin conformational changes that expose lipid droplet stores and facilitates translocation of phosphorylated HSL, thereby elevating the fat mobilization [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
