Hydrogen Sulfide in the Adipose Tissue—Physiology, Pathology and a Target for Pharmacotherapy

Abstract

Hydrogen sulfide (H2S) is synthesized in the adipose tissue mainly by cystathionine γ-lyase (CSE). Several studies have demonstrated that H2S is involved in adipogenesis, that is the differentiation of preadipocytes to adipocytes, most likely by inhibiting phosphodiesterases and increasing cyclic AMP concentration. The effect of H2S on adipose tissue insulin sensitivity and glucose uptake is controversial. Some studies suggest that H2S inhibits insulin-induced glucose uptake and that excess of H2S contributes to adipose tissue insulin resistance in metabolic syndrome. In contrast, other studies have demonstrated that H2S stimulates glucose uptake and its deficiency contributes to insulin resistance. Similarly, the effect of H2S on adipose tissue lipolysis is controversial. H2S produced by perivascular adipose tissue decreases vascular tone by activating ATP-sensitive and/or voltage-gated potassium channels in smooth muscle cells. Experimental obesity induced by high calorie diet has a time dependent effect on H2S in perivascular adipose tissue; short and long-term obesity increase and decrease H2S production, respectively. Hyperglycemia has been consistently demonstrated to suppress CSE-H2S pathway in various adipose tissue depots. Finally, H2S deficiency may contribute to adipose tissue inflammation associated with obesity/metabolic syndrome.

Nuclear factor erythroid 2-related factor 2 activation mediates hyperhomocysteinemia-associated lipolysis suppression in adipocytes

“…HHcy has been implicated as an independent risk factor of atherosclerosis, potentially via inducing oxidative stress on the endothelium of blood vessels, 28,29,30,31 which is counteracted by a series of antioxidants and detoxification enzymes, especially glutathione S-transferase (GSTs). 14 Nrf2 is an important transcription factor that regulates cellular anti-oxidative stress.…”

Regulation of vascular tone homeostasis by NO and H2S: Implications in hypertension

“…Four-aminopiridine (4-AP), which blocks many classes of K v channels other than K v 7, did not affect H 2 S-induced vasorelaxation while linopiridine, a rather selective K v 7 blocker, significantly reduced H 2 S-induced vasorelaxation in the rat thoracic aorta [3]. The molecular target for PAT-derived H 2 S in smooth muscle cells varies depending on the vessel size (reviewed in [159]). PAT-derived H 2 S induces hyperpolarization of adjacent VSM cells in large conduit and small resistance arteries by activating K ATP and K v 7.x channels, respectively [160].…”

Sulfur-containing gaseous signaling molecules

“…Вазодилататорна дія сірководню показана на різних судинах, починаючи з ізольованої аорти і включаючи мезентеріальні артерії людини [25]. Релаксацію судин спричиняє H 2 S, що синтезується в гладеньком'язових і ендотеліальних клітинах, а також у періадвентиціальній (периваскулярній) жировій тканині [23,26]. Механізм вазорелаксуючої дії H 2 S включає відкривання калієвих каналів, блокаду Са 2+ -каналів, підвищення продукції ендотелієм NO, ПГІ 2 та EDHF (endothelium-derived hyperpolarizing factor) і зниження рН [13].…”