Restricted accessResearch articleFirst published online 2021-08
Activation of Endogenous H 2 S Biosynthesis or Supplementation with Exogenous H 2 S Enhances Adipose Tissue Adipogenesis and Preserves Adipocyte Physiology in Humans
To investigate the impact of exogenous hydrogen sulfide (H2S) and its endogenous biosynthesis on human adipocytes and adipose tissue in the context of obesity and insulin resistance.
Results:
Experiments in human adipose tissue explants and in isolated preadipocytes demonstrated that exogenous H2S or the activation of endogenous H2S biosynthesis resulted in increased adipogenesis, insulin action, sirtuin deacetylase, and PPARγ transcriptional activity, whereas chemical inhibition and gene knockdown of each enzyme generating H2S (CTH, CBS, MPST) led to altered adipocyte differentiation, cellular senescence, and increased inflammation. In agreement with these experimental data, visceral and subcutaneous adipose tissue expression of H2S-synthesising enzymes was significantly reduced in morbidly obese subjects in association with attenuated adipogenesis and increased markers of adipose tissue inflammation and senescence. Interestingly, weight-loss interventions (including bariatric surgery or diet/exercise) improved the expression of H2S biosynthesis-related genes. In human preadipocytes, the expression of CTH, CBS, and MPST genes and H2S production were dramatically increased during adipocyte differentiation. More importantly, the adipocyte proteome exhibiting persulfidation was characterized, disclosing that different proteins involved in fatty acid and lipid metabolism, the citrate cycle, insulin signaling, several adipokines, and PPAR, experienced the most dramatic persulfidation (85–98%).
Innovation:
No previous studies investigated the impact of H2S on human adipose tissue. This study suggests that the potentiation of adipose tissue H2S biosynthesis is a possible therapeutic approach to improve adipose tissue dysfunction in patients with obesity and insulin resistance.
Conclusion:
Altogether, these data supported the relevance of H2S biosynthesis in the modulation of human adipocyte physiology. Antioxid. Redox Signal. 35, 319–340.
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References
1.
Acín-PérezR, IborraS, Martí-MateosY, CookECL, Conde-GarrosaR, PetcherskiA, MuñozMaM, Martínez de MenaR, KrishnanKC, JiménezC, BolañosJP, LaaksoM, LusisAJ, ShirihaiOS, SanchoD, and EnríquezJA. Fgr kinase is required for proinflammatory macrophage activation during diet-induced obesity. Nat Metab, 2: 974–988, 2020.
2.
AklMG, FawzyE, DeifM, FaroukA, and ElshorbagyAK. Perturbed adipose tissue hydrogen peroxide metabolism in centrally obese men: association with insulin resistance. PLoS One, 12: e0177268, 2017.
3.
AlbertJS, Yerges-ArmstrongLM, HorensteinRB, PollinTI, SreenivasanUT, ChaiS, BlanerWS, SnitkerS, O'ConnellJR, GongD-W, BreyerRJ, RyanAS, McLenithanJC, ShuldinerAR, SztalrydC, and DamcottCM. Null Mutation in Hormone-Sensitive Lipase Gene and Risk of Type 2 Diabetes. N Engl J Med, 370: 2307–2315, 2014.
4.
ArnerE, WestermarkPO, SpaldingKL, BrittonT, RydénM, FrisénJ, BernardS, and ArnerP. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes, 59: 105–109, 2010.
5.
ArocaA, BenitoJM, GotorC, and RomeroLC. Persulfidation proteome reveals the regulation of protein function by hydrogen sulfide in diverse biological processes in Arabidopsis. J Exp Bot, 68: 4915–4927, 2017.
6.
ArocaA, GotorC, and RomeroLC. Hydrogen sulfide signaling in plants: emerging roles of protein persulfidation. Front Plant Sci, 9: 1369, 2018.
7.
AsimakopoulouA, PanopoulosP, ChasapisCT, ColettaC, ZhouZ, CirinoG, GiannisA, SzaboC, SpyrouliasGA, and PapapetropoulosA. Selectivity of commonly used pharmacological inhibitors for cystathionine β synthase (CBS) and cystathionine γ lyase (CSE). Br J Pharmacol, 169: 922–932, 2013.
8.
BenavidesGA, SquadritoGL, MillsRW, PatelHD, IsbellTS, PatelRP, Darley-UsmarVM, DoellerJE, and KrausDW. Hydrogen sulfide mediates the vasoactivity of garlic. Proc Natl Acad Sci U S A, 104: 17977–17982, 2007.
9.
CaiJ, ShiX, WangH, FanJ, FengY, LinX, YangJ, CuiQ, TangC, XuG, and GengB. Cystathionine γ lyase–hydrogen sulfide increases peroxisome proliferator-activated receptor γ activity by sulfhydration at C139 site thereby promoting glucose uptake and lipid storage in adipocytes. Biochim Biophys Acta Mol Cell Biol Lipids, 1861: 419–429, 2016.
10.
CarobbioS, PellegrinelliV, and Vidal-PuigA. Adipose tissue function and expandability as determinants of lipotoxicity and the metabolic syndrome. Adv Exp Med Biol, 960: 161–196, 2017.
11.
ChakarounR, RaschpichlerM, KlötingN, OberbachA, FlehmigG, KernM, SchönMR, ShangE, LohmannT, DreßlerM, FasshauerM, StumvollM, and BlüherM. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism, 61: 706–714, 2012.
12.
ChalkiadakiA and GuarenteL. High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction. Cell Metab, 16: 180–188, 2012.
13.
ChattopadhyayM, KhemkaVK, ChatterjeeG, GangulyA, MukhopadhyayS, and ChakrabartiS. Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects. Mol Cell Biochem, 399: 95–103, 2015.
14.
ChengX, XiQY, WeiS, WuD, YeRS, ChenT, QiQE, JiangQY, WangSB, WangLN, ZhuXT, and ZhangYL. Critical role of miR-125b in lipogenesis by targeting stearoyl-CoA desaturase-1 (SCD-1). J Anim Sci, 94: 65–76, 2016.
15.
ChoiSA, ParkCS, KwonOS, GiongHK, LeeJS, HaTH, and LeeCS. Structural effects of naphthalimide-based fluorescent sensor for hydrogen sulfide and imaging in live zebrafish. Sci Rep, 6: 26203–26203, 2016.
ComasF, LatorreJ, OrtegaF, Arnoriaga RodríguezM, LluchA, SabaterM, RiusF, RibasX, CostasM, RicartW, LecubeA, Fernández-RealJM, and Moreno-NavarreteJM. Morbidly obese subjects show increased serum sulfide in proportion to fat mass. Int J Obes, 45: 415–426, 2020.
18.
ComasF, LatorreJ, OrtegaF, Oliveras-CañellasN, LluchA, RicartW, Fernández-RealJM, Moreno-NavarreteJM, OliveresN, LluchA, RicartW, Fernández-RealJM, and Moreno-NavarreteJM. Permanent cystathionine-β-Synthase gene knockdown promotes inflammation and oxidative stress in immortalized human adipose-derived mesenchymal stem cells, enhancing their adipogenic capacity. Redox Biol [Epub ahead of print]; DOI: 10.1016/j.redox.2020.101668, 2020.
19.
CuiY, LiuZ, SunX, HouX, QuB, ZhaoF, GaoX, SunZ, and LiQ. Thyroid hormone responsive protein spot 14 enhances lipogenesis in bovine mammary epithelial cells. Vitr Cell Dev Biol Anim, 51: 586–594, 2015.
20.
DasA, HuangGX, BonkowskiMS, LongchampA, LiC, SchultzMB, KimLJ, OsborneB, JoshiS, LuY, Treviño-VillarrealJH, KangMJ, HungT tyng, LeeB, WilliamsEO, IgarashiM, MitchellJR, WuLE, TurnerN, AranyZ, GuarenteL, and SinclairDA. Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular aging. Cell, 173: 74–89.e20, 2018.
21.
DingY, WangH, GengB, and XuG. Sulfhydration of perilipin 1 is involved in the inhibitory effects of cystathionine gamma lyase/hydrogen sulfide on adipocyte lipolysis. Biochem Biophys Res Commun, 521: 786–790, 2020.
22.
Dóka, IdaT, DagnellM, AbikoY, LuongNC, BalogN, TakataT, EspinosaB, NishimuraA, ChengQ, FunatoY, MikiH, FukutoJM, PriggeJR, SchmidtEE, ArnérESJ, KumagaiY, AkaikeT, and NagyP. Control of protein function through oxidation and reduction of persulfidated states. Sci Adv, 6: eaax8358, 2020.
23.
DuJ, HuangY, YanH, ZhangQ, ZhaoM, ZhuM, LiuJ, ChenSX, BuD, TangC, and JinH. Hydrogen sulfide suppresses oxidized low-density lipoprotein (Ox-LDL)-stimulated monocyte chemoattractant protein 1 generation from macrophages via the nuclear factor κb (NF-κB) pathway. J Biol Chem, 289: 9741–9753, 2014.
24.
ElrayessMA, AlmuraikhyS, KafienahW, Al-MenhaliA, Al-KhelaifiF, BashahM, ZarkovicK, ZarkovicN, WaegG, AlsayrafiM, and JaganjacM. 4-hydroxynonenal causes impairment of human subcutaneous adipogenesis and induction of adipocyte insulin resistance. Free Radic Biol Med, 104: 129–137, 2017.
25.
FilipovicMR.Persulfidation (S-sulfhydration) and H2S. Handb Exp Pharmacol, 230: 29–59, 2015.
26.
FuL, LiuK, HeJ, TianC, YuX, and YangJ. Direct proteomic mapping of cysteine persulfidation. Antioxidants Redox Signal, 33: 1061–1076, 2020.
27.
GarcíaI, Arenas-AlfonsecaL, MorenoI, GotorC, and RomeroLC. HCN regulates cellular processes through posttranslational modification of proteins by s-cyanylation. Plant Physiol, 179: 107–123, 2019.
28.
GengB, CaiB, LiaoF, ZhengY, ZengQ, FanX, GongY, YangJ, CuiQ hua, TangC, and XuG heng. Increase or decrease hydrogen sulfide exert opposite lipolysis, but reduce global insulin resistance in high fatty diet induced obese mice. PLoS One, 8: e73892–e73892, 2013.
GuptaS and KrugerWD. Cystathionine beta-synthase deficiency causes fat loss in mice. PLoS One, 6: e27598–e27598, 2011.
31.
GustafsonB, HedjazifarS, GoggS, HammarstedtA, and SmithU. Insulin resistance and impaired adipogenesis. Trends Endocrinol Metab, 26: 193–200, 2015.
32.
HineC, HarputlugilE, ZhangY, RuckenstuhlC, LeeBC, BraceL, LongchampA, Treviño-VillarrealJH, MejiaP, OzakiCK, WangR, GladyshevVN, MadeoF, MairWB, and MitchellJR. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell, 160: 132–144, 2015.
33.
KahnCR, WangG, and LeeKY. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest, 129: 3990–4000, 2019.
34.
KamounP.Endogenous production of hydrogen sulfide in mammals. Amino Acids, 26: 243–254, 2004.
35.
KatsoudaA, SzaboC, and PapapetropoulosA. Reduced adipose tissue H2S in obesity. Pharmacol Res, 128: 190–199, 2018.
36.
KhanahmadiM, ManafiB, TayebiniaH, KarimiJ, and KhodadadiI. Downregulation of sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease. EXCLI J, 19: 1387–1398, 2020.
37.
KrsticJ, ReinischI, SchuppM, SchulzTJ, and ProkeschA. P53 functions in adipose tissue metabolism and homeostasis. Int J Mol Sci, 19: 2622, 2018.
38.
KrugerWD.Cystathionine β-synthase deficiency: of mice and men. Mol Genet Metab, 121: 199–205, 2017.
39.
KuoMM, KimDH, JanduS, BergmanY, TanS, WangH, PandeyDR, AbrahamTP, ShoukasAA, BerkowitzDE, and SanthanamL. MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery. Am J Physiol Hear Circ Physiol, 310: H71–H79, 2016.
40.
KursaweR, NarayanD, CaliAMG, ShawM, PierpontB, ShulmanGI, and CaprioS. Downregulation of ADIPOQ and PPARγ2 gene expression in subcutaneous adipose tissue of obese adolescents with hepatic steatosis. Obesity, 18: 1911–1917, 2010.
41.
LeeZW, ZhouJ, ChenCS, ZhaoY, TanCH, LiL, MoorePK, and DengLW. The slow-releasing Hydrogen Sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo. PLoS One, 6: e21077, 2011.
42.
LevertKL, WaldropGL, and StephensJM. A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis. J Biol Chem, 277: 16347–16350, 2002.
43.
LiuT, MaX, OuyangT, ChenH, LinJ, LiuJ, XiaoY, YuJ, and HuangY. SIRT1 reverses senescence via enhancing autophagy and attenuates oxidative stress-induced apoptosis through promoting p53 degradation. Int J Biol Macromol, 117: 225–234, 2018.
44.
LiuZ, WuKKL, JiangX, XuA, and ChengKKY. The role of adipose tissue senescence in obesity and ageing-related metabolic disorders. Clin Sci, 134: 315–330, 2020.
45.
LongoM, ZatteraleF, NaderiJ, ParrilloL, FormisanoP, RacitiGA, BeguinotF, and MieleC. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int J Mol Sci, 20: 2358, 2019.
46.
LyuY, SuX, DengJ, LiuS, ZouL, ZhaoX, WeiS, GengB, and XuG. Defective differentiation of adipose precursor cells from lipodystrophic mice lacking perilipin 1. PLoS One, 10: e0117536, 2015.
47.
ManiS, YangG, and WangR. A critical life-supporting role for cystathionine γ-lyase in the absence of dietary cysteine supply. Free Radic Biol Med, 50: 1280–1287, 2011.
48.
MannaP and JainSK. 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 (A. J Biol Chem, 286: 39848–39859, 2011.
49.
MannaP and JainSK. Vitamin D up-regulates glucose transporter 4 (GLUT4) translocation and glucose utilization mediated by cystathionine-γ-lyase (CSE) activation and H2S formation in 3T3L1 adipocytes. J Biol Chem, 287: 42324–42332, 2012.
50.
MasschelinPM, CoxAR, ChernisN, and HartigSM.The Impact of Oxidative Stress on Adipose Tissue Energy Balance. Front Physiol, 10, 2020.
51.
MillerDL and RothMB. Hydrogen sulfide increases thermotolerance and lifespan in Caenorhabditis elegans. Proc Natl Acad Sci U S A, 104: 20618–20622, 2007.
52.
MinaminoT, OrimoM, ShimizuI, KuniedaT, YokoyamaM, ItoT, NojimaA, NabetaniA, OikeY, MatsubaraH, IshikawaF, and KomuroI. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med, 15: 1082–1087, 2009.
53.
Moreno-NavarreteJM, EscotéX, OrtegaF, SerinoM, CampbellM, MichalskiM-CC, LavilleM, XifraG, LucheE, DomingoP, SabaterM, PardoG, WagetA, SalvadorJ, GiraltM, Rodriguez-HermosaJI, CampsM, KolditzCI, ViguerieN, GalitzkyJ, DecaunesP, RicartW, FrühbeckG, VillarroyaF, MingroneG, LanginD, ZorzanoA, VidalH, VendrellJ, BurcelinR, Vidal-PuigA, and Fernández-RealJM. A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction. Diabetologia, 56: 2524–2537, 2013.
54.
Moreno-NavarreteJM, OrtegaF, SerranoM, Rodriguez-HermosaJI, RicartW, MingroneG, and Fernández-RealJM. CIDEC/FSP27 and PLIN1 gene expression run in parallel to mitochondrial genes in human adipose tissue, both increasing after weight loss. Int J Obes, 38: 865–872, 2014.
55.
MorleyTS, XiaJY, and SchererPE. Selective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements. Nat Commun, 6: 7906, 2015.
56.
NagaharaN, NirasawaT, YoshiiT, and NiimuraY. Is novel signal transducer sulfur oxide involved in the redox cycle of persulfide at the catalytic site cysteine in a stable reaction intermediate of mercaptopyruvate sulfurtransferase?. Antioxidants Redox Signal, 16: 747–753, 2012.
57.
OrtegaFJ, MercaderJM, Moreno-NavarreteJM, NonellL, PuigdecanetE, Rodriquez-HermosaJI, RoviraO, XifraG, GuerraE, MorenoM, MayasD, Moreno-CastellanosN, Fernández-FormosoJA, RicartW, TinahonesFJ, TorrentsD, MalagónMM, and Fernández-RealJM. Surgery-induced weight loss is associated with the downregulation of genes targeted by MicroRNAs in adipose tissue. J Clin Endocrinol Metab, 100: E1467–E1476, 2015.
58.
PadiyaR, KhatuaTN, BagulPK, KunchaM, and BanerjeeSK. Garlic improves insulin sensitivity and associated metabolic syndromes in fructose fed rats. Nutr Metab, 8: 53, 2011.
59.
PanZ, WangH, LiuY, YuC, ZhangY, ChenJ, WangX, and GuanQ. Involvement of CSE/H2S in high glucose induced aberrant secretion of adipokines in 3T3-L1 adipocytes. Lipids Health Dis, 13: 155, 2014.
60.
PaulBD and SnyderSH. H 2S signalling through protein sulfhydration and beyond. Nat Rev Mol Cell Biol, 13: 499–507, 2012.
61.
Pérez-PérezR, LópezJA, García-SantosE, CamafeitaE, Gómez-SerranoM, Ortega-DelgadoFJ, RicartW, Fernández-RealJM, and PeralB. Uncovering suitable reference proteins for expression studies in human adipose tissue with relevance to obesity. PLoS One, 7: e30326, 2012.
62.
Politis-BarberV, BrunettaHS, PaglialungaS, PetrickHL, and HollowayGP. Long-term, high-fat feeding exacerbates short-term increases in adipose mitochondrial reactive oxygen species, without impairing mitochondrial respiration. Am J Physiol Endocrinol Metab, 319: E373–E387, 2020.
63.
PowellCR, DillonKM, and MatsonJB. A review of hydrogen sulfide (H2S) donors: chemistry and potential therapeutic applications. Biochem Pharmacol, 149: 110–123, 2018.
64.
RappouE, JukarainenS, Rinnankoski-TuikkaR, KayeS, HeinonenS, HakkarainenA, LundbomJ, LundbomN, SaunavaaraV, RissanenA, VirtanenKA, PirinenE, and PietiläinenKH. Weight Loss Is Associated With Increased NAD+/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue. J Clin Endocrinol Metab, 101: 1263–1273, 2016.
65.
Sanokawa-AkakuraR, AkakuraS, and TabibzadehS. Replicative senescence in human fibroblasts is delayed by hydrogen sulfide in a NAMPT/SIRT1 dependent manner. PLoS One, 11: e0164710–e0164710, 2016.
66.
SchmidB, RippmannJF, TadayyonM, and HamiltonBS. Inhibition of fatty acid synthase prevents preadipocyte differentiation. Biochem Biophys Res Commun, 328: 1073–1082, 2005.
67.
ShearinAL, MonksBR, SealeP, and BirnbaumMJ. Lack of AKT in adipocytes causes severe lipodystrophy. Mol Metab, 5: 472–479, 2016.
68.
ShibuyaN, TanakaM, YoshidaM, OgasawaraY, TogawaT, IshiiK, and KimuraH. 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxidants Redox Signal, 11: 703–714, 2009.
69.
SpassovSG, DonusR, IhlePM, EngelstaedterH, HoetzelA, and FallerS. Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury. Oxid Med Cell Longev, 2017: 3715037, 2017.
70.
SzabóC.Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov, 6: 917–935, 2007.
71.
TinahonesFJ, AraguezLCI, MurriM, OliveraWO, TorresMDM, BarbarrojaN, HuelgasRG, MalagónMM, and Bekay REl. Caspase induction and BCL2 inhibition in human adipose tissue. Diabetes Care, 36: 513–521, 2013.
72.
TrayhurnP.Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev, 93: 1–21, 2013.
73.
TsaiCY, PehMT, FengW, DymockBW, and MoorePK. Hydrogen sulfide promotes adipogenesis in 3T3L1 cells. PLoS One, 10: e0119511–e0119511, 2015.
74.
VeilleuxA, BlouinK, RhéaumeC, DarisM, MaretteA, and TchernofA. Glucose transporter 4 and insulin receptor substrate-1 messenger RNA expression in omental and subcutaneous adipose tissue in women. Metabolism, 58: 624–631, 2009.
75.
VizcaínoJA, CsordasA, del-ToroN, DianesJA, GrissJ, LavidasI, MayerG, Perez-RiverolY, ReisingerF, TernentT, XuQ-W, WangR, and HermjakobH. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res, 44: D447–D456, 2016.
76.
VowinckelJ, CapuanoF, CampbellK, DeeryMJ, LilleyKS, and RalserM. The beauty of being (label)-free: sample preparation methods for SWATH-MS and next-generation targeted proteomics. F1000Research, 2: 272, 2014.
77.
WhitemanM, GoodingKM, WhatmoreJL, BallCI, MawsonD, SkinnerK, TookeJE, and ShoreAC. Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide. Diabetologia, 53: 1722–1726, 2010.
78.
XuC, CaiY, FanP, BaiB, ChenJ, DengHB, CheCM, XuA, VanhouttePM, and WangY. Calorie restriction prevents metabolic aging caused by abnormal sirt1 function in adipose tissues. Diabetes, 64: 1576–1590, 2015.
79.
XueR, HaoDD, SunJP, LiWW, ZhaoMM, LiXH, ChenY, ZhuJH, DingYJ, LiuJ, and ZhuYC. Hydrogen sulfide treatment promotes glucose uptake by increasing insulin receptor sensitivity and ameliorates kidney lesions in type 2 diabetes. Antioxidants Redox Signal, 19: 5–23, 2013.
80.
YangG, JuY, FuM, ZhangY, PeiY, RacineM, BaathS, MerrittTJS, WangR, and WuL. Cystathionine gamma-lyase/hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice. Biochim Biophys Acta Mol Cell Biol Lipids, 1863: 165–176, 2018.
81.
YangG, WuL, JiangB, YangW, QiJ, CaoK, MengQ, MustafaAK, MuW, ZhangS, SnyderSH, and WangR. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine γ-lyase. Science (80-), 322: 587–590, 2008.
82.
ZhanT, PoppelreutherM, EhehaltR, and FüllekrugJ.Overexpressed FATP1, ACSVL4/FATP4 and ACSL1 Increase the Cellular Fatty Acid Uptake of 3T3-L1 adipocytes but are localized on intracellular membranes. PLoS One 7: e45087, 2012.
83.
ZhangD, MacInkovicI, Devarie-BaezNO, PanJ, ParkCM, CarrollKS, FilipovicMR, and XianM. Detection of protein S-sulfhydration by a tag-switch technique. Angew Chemie - Int Ed, 53: 575–581, 2014.
American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care, 38: S8–S16, 2015.
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