Role of Hydrogen Sulfide and Polysulfides in the Regulation of Lipolysis in the Adipose Tissue: Possible Implications for the Pathogenesis of Metabolic Syndrome.

Jerzy Bełtowski,Krzysztof Wiórkowski

doi:10.3390/ijms23031346

Jerzy Bełtowski, Krzysztof Wiórkowski

Open Access

https://doi.org/10.3390/ijms23031346

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Abstract

Hydrogen sulfide (H2S) and inorganic polysulfides are important signaling molecules; however, little is known about their role in the adipose tissue. We examined the effect of H2S and polysulfides on adipose tissue lipolysis. H2S and polysulfide production by mesenteric adipose tissue explants in rats was measured. The effect of Na2S and Na2S4, the H2S and polysulfide donors, respectively, on lipolysis markers, plasma non-esterified fatty acids (NEFA) and glycerol, was examined. Na2S but not Na2S4 increased plasma NEFA and glycerol in a time- and dose-dependent manner. Na2S increased cyclic AMP but not cyclic GMP concentration in the adipose tissue. The effect of Na2S on NEFA and glycerol was abolished by the specific inhibitor of protein kinase A, KT5720. The effect of Na2S on lipolysis was not abolished by propranolol, suggesting no involvement of β-adrenergic receptors. In addition, Na2S had no effect on phosphodiesterase activity in the adipose tissue. Obesity induced by feeding rats a highly palatable diet for 1 month was associated with increased plasma NEFA and glycerol concentrations, as well as greater H2S production in the adipose tissue. In conclusion, H2S stimulates lipolysis and may contribute to the enhanced lipolysis associated with obesity.

Highlights

Adipose tissue is one of the most abundant tissues in human body
Very small amounts of H2S and H2Sn were produced by adipose tissue in the absence of L-cysteine (L-Cys) and pyridoxal 5 -phosphate (PLP), which are the substrate and cofactor, respectively, of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE)
Inhibitors of mercaptopyruvate sulfurtransferase (MST), L-aspartate and phenylpyruvate, reduced H2S and H2Sn production in the presence of 3-MP but had no effect on H2S production in the presence of L-Cys and pyridoxal -phosphate (PLP). These results suggest that H2S is produced in the adipose tissue mainly by CSE and, to a lesser extent, by MST, whereas the latter enzyme is responsible for polysulfide production (Figure 1)

Summary

Introduction

Adipose tissue is one of the most abundant tissues in human body. For a long time considered only as a passive site of energy storage, adipose tissue is recognized as a very active metabolic and endocrine organ. Fatty acids liberated from triglycerides stored in the adipose tissue represent an important source of energy for many organs. Perivascular adipose tissue (PVAT), which surrounds the blood vessels, produces vasodilating and anti-inflammatory mediators, which have an important role in maintaining vascular homeostasis; obesity is associated with PVAT dysfunction due to its inflammation and local oxidative stress [5,6]. Research interest in adipose tissue has expanded due to increasing prevalence of obesity and metabolic syndrome, which is a cluster of obesity-associated abnormalities such as dyslipidemia, impaired glucose tolerance/Type 2 diabetes, arterial hypertension, chronic prothrombotic and pro-inflammatory states, all of which contribute to the development of atherosclerosis, ischemic heart disease, heart failure, nephropathy, neuroinflammation and certain cancers [1,9,10]

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