Hydrogen Sulfide, Adipose Tissue and Diabetes Mellitus

Figures & data

Figure 1 Generalised overview of H₂S production in the cell. The endogenous production of H₂S occurs via two main pathways-reverse transsulfuration and cysteine oxidation which take place partly inside mitochondria.

Figure 2 (A) Healthy and obese adipose tissue. Obese adipose tissue is characterized by inflammation and progressive infiltration by macrophages as obesity develops. (B) The anti-inflammation effect of H₂S on obese adipose tissue.

Figure 3 The bilateral regulation of H₂S on glucose metabolism and insulin sensitivity in adipocytes.

Figure 4 Generalised overview of the effects of H₂S on adipocyte lipolysis and adipogenesis.

Figure 5 The mechanisms of the vasorelaxation effect of adipocytes-derived and exogenous H₂S.

Table 1 Multiple Products Called Adipokines Involving Different Biological Processes Expressed and Secreted by White Adipose Tissue May Act at Both the Systemic (Endocrine) and Local (Autocrine and/Or Paracrine) Levels

Effects On	Adipokine	Full Name
Inflammation	IL-1Rα	Interleukin-1 Receptor α
	IL-1β	Interleukin-1β
	IL-8	Interleukin-8
	IL-10	Interleukin-10
	CRP	C-reactive protein
	MCP-1	Monocyte chemotactic protein1
	OPN	Osteopontin
	Visfatin
Glucose metabolism	FFA	Free fatty acids
	Resistin
Lipid metabolism	ApoE	Apolipoprotein E
	LPL	Lipoprotein lipase
	Glycerol
	CD36	Leukocyte differentiation antigen CD36
	HSL/ATGL	Hormone-sensitive lipase/Adipose triglyceride lipase
Vasoactive factors	Angiotensinogen
	Adiponectin
	PAI-1	Plasminogen activator inhibitor 1
	VEGF	Vascular endothelial growth factor
	Tissue factors
	NO	Nitric oxide
Growth factors	TGF-β	Transforming growth factor β
	IGF-1	Insulin-like growth factor 1
	HGF	Hepatocyte growth factor
	NGF	Nerve growth factor
	LIF	Leukaemia-inhibitory factor
	Fibronectin
Immune response	Adipsin
	ASP	Acylation stimulating protein
	Factors B and C3
	CSFs	Colony-stimulating factor
	IL-17D	Interleukin-17D
	SAA3	Serum amyloid A3
Cytokines	Leptin
	TNF-α	Tumour necrosis factor α
	Chemerin
Other proteins	CAV-1	Caveolin 1
	AQP-7	Aquaporin 7
	RBP-4	Retinol binding protein 4
	LCN-2	Lipocalin-2

Figure 6 The mechanisms of adipocytes apoptosis in obese adipose tissue and the anti-apoptosis effect of H₂S.

Table 2 Effects of H₂S on Adipose Tissue/Adipocyte Pathophysiological Functions

Adipose Tissue/Adipocyte Pathophysiological Function	Effects of H2S	References
Inflammation	Anti-inflammation	^Citation41,Citation42,Citation112
Insulin resistance	Ameliorate insulin resistance	^Citation53,Citation54,Citation56,Citation57,Citation64
	Exacerbate insulin resistance	^Citation21,Citation52
Lipogenesis/lipolysis	Promote lipogenesis	^Citation62^–^Citation64
	Reduce lipolysis	^Citation57,Citation64
Vascular tone	Anti-contractile	^Citation22,Citation71,Citation73^-^Citation75
	Pro-contractile	^Citation75
Adipokines	Abnormal secretion	^Citation41
Apoptosis	Anti-apoptosis	^Citation107

Pan Z, Wang H, Liu Y, et al. Involvement of CSE/H2S in high glucose induced aberrant secretion of adipokines in 3T3-L1 adipocytes. Lipids Health Dis. 2014;13(1):155. doi:10.1186/1476-511X-13-155

 PubMedGoogle Scholar

Velmurugan GV, Huang H, Sun H, et al. Depletion of H2S during obesity enhances store-operated Ca2+entry in adipose tissue macrophages to increase cytokine production. Sci Signal. 2015;8(407):ra128. doi:10.1126/scisignal.aac7135

 PubMedGoogle Scholar

Stein A, Bailey SM. Redox biology of hydrogen sulfide: implications for physiology, pathophysiology, and pharmacology. Redox Biol. 2013;1(1):32–39. doi:10.1016/j.redox.2012.11.006

 PubMedGoogle Scholar

Manna P, Jain SK. Vitamin D up-regulates glucose transporter 4 (GLUT4) translocation and glucose utilization mediated by cystathionine-gamma-lyase (CSE) activation and H2S formation in 3T3L1 adipocytes. J Biol Chem. 2012;287:42324–42332. doi:10.1074/jbc.M112.407833

 PubMed Web of Science ®Google Scholar

Manna P, Jain SK. Hydrogen sulfide and L-cysteine increase phosphatidylinositol 3,4,5-trisphosphate (PIP3) and glucose utilization by inhibiting phosphatase and tensin homolog (PTEN) protein and activating phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/protein kinase Czeta/lambda (PKCzeta/lambda) in 3T3l1 adipocytes. J Biol Chem. 2011;286:39848–39859.

 PubMed Web of Science ®Google Scholar

Xue R, Hao DD, Sun JP, et al. Hydrogen sulfide treatment promotes glucose uptake by increasing insulin receptor sensitivity and ameliorates kidney lesions in type 2 diabetes. Antioxid Redox Signal. 2013;19:5–23. doi:10.1089/ars.2012.5024

 PubMed Web of Science ®Google Scholar

Geng B, Cai B, Liao F, et al. Increase or decrease hydrogen sulfide exert opposite lipolysis, but reduce global insulin resistance in high fatty diet induced obese mice. PLoS One. 2013;8(9):e73892. doi:10.1371/journal.pone.0073892

 PubMed Web of Science ®Google Scholar

Cai J, Shi X, Wang H, et al. Cystathionine gamma lyase-hydrogen sulfide increases peroxisome proliferator-activated receptor gamma activity by sulfhydration at C139 site thereby promoting glucose uptake and lipid storage in adipocytes. Biochim Biophys Acta. 2016;1861:419–429. doi:10.1016/j.bbalip.2016.03.001

 PubMed Web of Science ®Google Scholar

Feng X, Chen Y, Zhao J, Tang C, Jiang Z, Geng B. Hydrogen sulfide from adipose tissue is a novel insulin resistance regulator. Biochem Biophys Res Commun. 2009;380(1):153–159. doi:10.1016/j.bbrc.2009.01.059

 PubMed Web of Science ®Google Scholar

Huang CY, Yao WF, Wu WG, Lu YL, Wan H, Wang W. Endogenous CSE/H2 S system mediates TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes. Cell Biochem Funct. 2013;31:468–475. doi:10.1002/cbf.2920

 PubMedGoogle Scholar

Tsai CY, Peh MT, Feng W, Dymock BW, Moore PK. Hydrogen sulfide promotes adipogenesis in 3T3L1 cells. PLoS One. 2015;10:e0119511. doi:10.1371/journal.pone.0119511

 PubMed Web of Science ®Google Scholar

Fang L, Zhao J, Chen Y, et al. Hydrogen sulfide derived from periadventitial adipose tissue is a vasodilator. J Hypertens. 2009;27(11):2174–2185. doi:10.1097/HJH.0b013e328330a900

 PubMed Web of Science ®Google Scholar

Stasko A, Brezova V, Zalibera M, Biskupic S, Ondrias K. Electron transfer: a primary step in the reactions of sodium hydrosulphide, an H2S/HS−donor. Free Radic Res. 2009;43(6):581–593. doi:10.1080/10715760902977416

 PubMed Web of Science ®Google Scholar

Schleifenbaum J, Kohn C, Voblova N, et al. Systemic peripheral artery relaxation by KCNQ channel openers and hydrogen sulfide. J Hypertens. 2010;28(9):1875–1882. doi:10.1097/HJH.0b013e32833c20d5

 PubMed Web of Science ®Google Scholar

Emilova R, Dimitrova D, Mladenov M, Daneva T, Schubert R, Gagov H. Cystathionine gamma-lyase of perivascular adipose tissue with reversed regulatory effect in diabetic rat artery. Biotechnol Biotechnol Equip. 2015;29(1):147–151. doi:10.1080/13102818.2014.991565

 PubMed Web of Science ®Google Scholar

Aykan A, Ozturk S, Sahin I, Avcu F, Sagkan RI, Isik S. The effects of hydrogen sulfide on adipocyte viability in human adipocyte and adipocyte-derived mesenchymal stem cell cultures under ischemic conditions. Ann Plast Surg. 2015;75(6):657–665. doi:10.1097/SAP.0000000000000595

 PubMedGoogle Scholar