El-Sayed Moustafa, J. S. & Froguel, P. From obesity genetics to the future of personalized obesity therapy. Nat. Rev. Endocrinol. 9, 402–413 (2013).
Froguel, P. & Blakemore, A. I. The power of the extreme in elucidating obesity. N. Engl. J. Med. 359, 891–893 (2008).
Saeed, S. et al. Novel LEPR mutations in obese Pakistani children identified by PCR-based enrichment and next-generation sequencing. Obesity (Silver Spring) 22, 1112–1117 (2014).
Saeed, S. et al. Genetic variants in LEP, LEPR and MC4R explain 30% of severeobesity in children from a consanguineous population. Obesity (Silver Spring) 23, 1687–1695 (2015).
Saeed, S., Butt, T. A., Anwer, M., Arslan, M. & Froguel, P. High prevalence of leptin and melanocortin-4 receptor gene mutations in children with severe obesity from Pakistani consanguineous families. Mol. Genet. Metab. 106, 121–126 (2012).
Kopelman, P. G. Obesity as a medical problem. Nature 404, 635–643 (2000).
World Health Organization. A Snapshot of Global Health (World Health Organization, Geneva, 2012).
Stunkard, A. J., Harris, J. R., Pedersen, N. L. & McClearn, G. E. The body mass index of twins who have been reared apart. N. Engl. J. Med. 322, 1483–1487 (1990).
Wang, Z. et al. Adult type 3 adenylyl-cyclase-deficient mice are obese. PLoS One 4, e6979 (2009).
Wong, S. T. et al. Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Neuron 27, 487–497 (2000).
Cao, H., Chen, X., Yang, Y. & Storm, D. R. Disruption of type 3 adenylyl cyclase expression in the hypothalamus leads to obesity. Integr Obes Diabetes 2, 225–228 (2016).
Pitman, J. L. et al. A gain-of-function mutation in adenylate cyclase 3 protects mice from diet-induced obesity. PLoS One 9, e110226 (2014).
Hanoune, J. & Defer, N. Regulation and role of adenylyl cyclase isoforms. Annu. Rev. Pharmacol. Toxicol. 41, 145–174 (2001).
Kanoski, S. E., Fortin, S. M., Arnold, M., Grill, H. J. & Hayes, M. R. Peripheral and central GLP1 receptor populations mediate the anorectic effects of peripherally administered GLP1 receptor agonists, liraglutide and exendin-4. Endocrinology 152, 3103–3112 (2011).
Liang, Y. et al. Hepatic adenylate cyclase 3 is upregulated by liraglutide and subsequently plays a protective role in insulin resistance and obesity. Nutr. Diabetes 6, e191 (2016).
Ando, T. et al. Liraglutide as a potentially useful agent for regulating appetite in diabetic patients with hypothalamic hyperphagia and obesity. Intern. Med. 53, 1791–1795 (2014).
Madsen, L. & Kristiansen, K. The importance of dietary modulation of cAMP and insulin signaling in adipose tissue and the development of obesity. Ann. NY Acad. Sci. 1190, 1–14 (2010).
Tong, T., Shen, Y., Lee, H. W., Yu, R. & Park, T. Adenylyl cyclase 3 haplo-insufficiency confers susceptibility to diet-induced obesity and insulin resistance in mice. Sci. Rep. 6, 34179 (2016).
Warrington, N. M. et al. A genome-wide association study of body mass index across early life and childhood. Int. J. Epidemiol. 44, 700–712 (2015).
Speliotes, E. K. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 42, 937–948 (2010).
Wen, W. et al. Meta-analysis identifies common variants associated with body mass index in east Asians. Nat. Genet. 44, 307–311 (2012).
Monda, K. L. et al. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat. Genet. 45, 690–696 (2013).
Stergiakouli, E. et al. Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3. Obesity (Silver Spring) 22, 2252–2259 (2014).
Felix, J. F. et al. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Hum. Mol. Genet. 25, 389–403 (2016).
Liu, J. Z. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat. Genet. 47, 979–986 (2015).
Voisin, S. et al. Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers. Genome Med. 7, 103 (2015).
Liu, X. et al. Maternal preconception body mass index and offspring cord blood DNA methylation: exploration of early life origins of disease. Environ. Mol. Mutagen. 55, 223–230 (2014).
Trott, O. & Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J. Comput. Chem. 31, 455–461 (2010).
Boal, F., Laguerre, M., Milochau, A., Lang, J. & Scotti, P. A. A charged prominence in the linker domain of the cysteine-string protein Cspα mediates its regulated interaction with the calcium sensor synaptotagmin 9 during exocytosis. FASEB J. 25, 132–143 (2011).
Roger, B. et al. Adenylyl cyclase 8 is central to glucagon-like peptide 1 signaling and effects of chronically elevated glucose in rat and human pancreatic beta cells. Diabetologia 54, 390–402 (2011).
Ferdaoussi, M. et al. Exendin-4 protects beta cells from interleukin-1β-induced apoptosis by interfering with the c-Jun NH2-terminal kinase pathway. Diabetes 57, 1205–1215 (2008).