Flegal, K.M., Carroll, M.D., Ogden, C.L. & Curtin, L.R. Prevalence and trends in obesity among US adults, 1999–2008. J. Am. Med. Assoc. 303, 235–241 (2010).
Yanovski, S.Z. & Yanovski, J.A. Obesity prevalence in the United States—up, down or sideways? N. Engl. J. Med. 364, 987–989 (2011).
Ljungvall, A. & Zimmerman, F.J. Bigger bodies: long-term trends and disparities in obesity and body-mass index among U.S. adults, 1960–2008. Soc. Sci. Med. 75, 109–119 (2012).
Morton, N.M. et al. A polygenic model of the metabolic syndrome with reduced circulating and intra-adipose glucocorticoid action. Diabetes 54, 3371–3378 (2005).
Horvat, S. et al. Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content. Mamm. Genome 11, 2–7 (2000).
Prevorsek, Z., Gorjanc, G., Paigen, B. & Horvat, S. Congenic and bioinformatics analyses resolved a major-effect Fob3b QTL on mouse chr 15 into two closely linked loci. Mamm. Genome 21, 172–185 (2010).
Bünger, L. et al. Long-term divergent selection on fatness in mice indicates a regulation system independent of leptin production and reception. FASEB J. 17, 85–87 (2003).
Morton, N.M. et al. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. PLoS One 6, e23944 (2011).
Westley, J. Rhodanese. Adv. Enzymol. 39, 327–368 (1973).
Hall, A.H., Saiers, J. & Baud, F. Which cyanide antidote? Crit. Rev. Toxicol. 39, 541–552 (2009).
Bonomi, F., Pagani, S., Cerletti, P. & Cannella, C. Rhodanese-mediated sulfur transfer to succinate dehydrogenase. Eur. J. Biochem. 72, 17–24 (1977).
Pagani, S. & Galante, Y.M. Interaction of rhodanese with mitochondrial NADH dehydrogenase. Biochim. Biophys. Acta 742, 278–284 (1983).
Nandi, D.L., Horowitz, P.M. & Westley, J. Rhodanese as a thioredoxin oxidase. Int. J. Biochem. Cell Biol. 32, 465–473 (2000).
Wang, R. Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol. Rev. 92, 791–896 (2012).
Tiranti, V. et al. Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy. Nat. Med. 15, 200–205 (2009).
Smirnov, A. et al. Mitochondrial enzyme rhodanese is essential for 5 S ribosomal RNA import into human mitochondria. J. Biol. Chem. 285, 30792–30803 (2010).
Vernochet, C. et al. Adipose-specific deletion of Tfam increases mitochondrial oxidation and protects mice against obesity and insulin resistance. Cell Metab. 16, 765–776 (2012).
Tormos, K.V. et al. Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab. 14, 537–544 (2011).
Kusminski, C.M. et al. MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity. Nat. Med. 18, 1539–1549 (2012).
Geng, B. et al. Increase or decrease hydrogen sulfide exert opposite lipolysis but reduce global insulin resistance in high-fat-diet-induced obese mice. PLoS One 8, e73892 (2013).
Feng, X. et al. Hydrogen sulfide from adipose tissue is a novel insulin resistance regulator. Biochem. Biophys. Res. Commun. 380, 153–159 (2009).
Simoncic, M. et al. Divergent physical activity and novel alternative responses to high-fat feeding in polygenic fat and lean mice. Behav. Genet. 38, 292–300 (2008).
Svenson, K.L. et al. High-resolution genetic mapping using the Mouse Diversity outbred population. Genetics 190, 437–447 (2012).
Wang, Z.V., Deng, Y., Wang, Q.A., Sun, K. & Scherer, P.E. Identification and characterization of a promoter cassette conferring adipocyte-specific gene expression. Endocrinology 151, 2933–2939 (2010).
Xu, A. et al. The fat-derived hormone adiponectin alleviates alcoholic and non-alcoholic fatty liver diseases in mice. J. Clin. Invest. 112, 91–100 (2003).
Herman, M.A. et al. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature 484, 333–338 (2012).
Sen, U. et al. Cardioprotective role of sodium thiosulfate on chronic heart failure by modulating endogenous H2S generation. Pharmacology 82, 201–213 (2008).
Sabelli, R. et al. Rhodanese–thioredoxin system and allyl sulfur compounds. FEBS J. 275, 3884–3899 (2008).
Koh, E.H. et al. Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes 56, 2973–2981 (2007).
Emilsson, V. et al. Genetics of gene expression and its effect on disease. Nature 452, 423–428 (2008).
Moreno-Navarrete, J.M. et al. Decreased RB1 mRNA, protein and activity reflect obesity-induced altered adipogenic capacity in human adipose tissue. Diabetes 62, 1923–1931 (2013).
Wabitsch, M. et al. Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation. Int. J. Obes. Relat. Metab. Disord. 25, 8–15 (2001).
Loos, R.J. The genetic epidemiology of melanocortin 4 receptor variants. Eur. J. Pharmacol. 660, 156–164 (2011).
Smemo, S. et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507, 371–375 (2014).
Kilpeläinen, T.O. et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat. Genet. 43, 753–760 (2011).
Heid, I.M. et al. Meta-analysis identifies 13 new loci associated with waist–hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat. Genet. 42, 949–960 (2010).
Rung, J. et al. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat. Genet. 41, 1110–1115 (2009).
Vigouroux, C., Caron-Debarle, M., Le Dour, C., Magré, J. & Capeau, J. Molecular mechanisms of human lipodystrophies: from adipocyte lipid droplet to oxidative stress and lipotoxicity. Int. J. Biochem. Cell Biol. 43, 862–876 (2011).
Jacquemont, S. et al. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature 478, 97–102 (2011).
Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homolog. Nature 372, 425–432 (1994).
Mathes, W.F., Kelly, S.A. & Pomp, D. Advances in comparative genetics: influence of genetics on obesity. Br. J. Nutr. 106 (suppl. 1), S1–S10 (2011).
Soloveva, V., Graves, R.A., Rasenick, M.M., Spiegelman, B.M. & Ross, S.R. Transgenic mice overexpressing the β1-adrenergic receptor in adipose tissue are resistant to obesity. Mol. Endocrinol. 11, 27–38 (1997).
Harms, M. & Seale, P. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 19, 1252–1263 (2013).
Hawley, S.A. et al. The ancient drug salicylate directly activates AMP-activated protein kinase. Science 336, 918–922 (2012).
Hawley, S.A. et al. Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab. 11, 554–565 (2010).
Munger, S.C. et al. RNA-seq alignment to individualized genomes improves transcript abundance estimates in multiparent populations. Genetics 198, 59–73 (2014).
Steele, R., Wall, J.S., De Bodo, R.C. & Altszuler, N. Measurement of size and turnover rate of body glucose pool by the isotope-dilution method. Am. J. Physiol. 187, 15–24 (1956).
Hildebrandt, T.M. & Grieshaber, M.K. Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria. FEBS J. 275, 3352–3361 (2008).