Danaei, G. et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378, 31â€"40 (2011).
Wild, S., Roglic, G., Green, A., Sicree, R. & King, H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27, 1047â€"1053 (2004).
Carey, A. L. et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes 55, 2688â€"2697 (2006).
Watt, M. J. et al. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat. Med. 12, 541â€"548 (2006).
Steinberg, G. R. et al. Ciliary neurotrophic factor suppresses hypothalamic AMP-kinase signaling in leptin-resistant obese mice. Endocrinology 147, 3906â€"3914 (2006).
Matthews, V. B. et al. Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia 53, 2431â€"2441 (2010).
ACTS. A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. ALS CNTF Treatment Study Group. Neurology 46, 1244â€"1249 (1996).
Duff, E. & Baile, C. A. Ciliary neurotrophic factor: a role in obesity? Nutr. Rev. 61, 423â€"426 (2003).
Ettinger, M. P. et al. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized, dose-ranging study. J. Am. Med. Assoc. 289, 1826â€"1832 (2003).
Febbraio, M. A. Role of interleukins in obesity: implications for metabolic disease. Trends Endocrinol. Metab. 25, 312â€"319 (2014).
Kraakman, M. J. et al. Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance. Cell Metab. 21, 403â€"416 (2015).
Rabe, B. et al. Transgenic blockade of interleukin 6 transsignaling abrogates inflammation. Blood 111, 1021â€"1028 (2008).
Febbraio, M. A. gp130 receptor ligands as potential therapeutic targets for obesity. J. Clin. Invest. 117, 841â€"849 (2007).
Kallen, K. J. et al. Receptor recognition sites of cytokines are organized as exchangeable modules. Transfer of the leukemia inhibitory factor receptor-binding site from ciliary neurotrophic factor to interleukin-6. J. Biol. Chem. 274, 11859â€"11867 (1999).
Rakemann, T. et al. The designer cytokine hyper-interleukin-6 is a potent activator of STAT3-dependent gene transcription in vivo and in vitro. J. Biol. Chem. 274, 1257â€"1266 (1999).
Harris, J. M. & Chess, R. B. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2, 214â€"221 (2003).
Jazayeri, J. A. & Carroll, G. J. Fc-based cytokines: prospects for engineering superior therapeutics. BioDrugs 22, 11â€"26 (2008).
Srikanthan, P. & Karlamangla, A. S. Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J. Clin. Endocrinol. Metab. 96, 2898â€"2903 (2011).
Taniguchi, K. et al. A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature 519, 57â€"62 (2015).
Watt, K. I. et al. The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size. Nat. Commun. 6, 6048 (2015).
Grey, A. Thiazolidinedione-induced skeletal fragility-mechanisms and implications. Diabetes Obes. Metab. 11, 275â€"284 (2009).
Mannaerts, I. et al. The Hippo pathway effector YAP controls mouse hepatic stellate cell activation. J. Hepatol. 63, 679â€"688 (2015).
Ellingsgaard, H. et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat. Med. 17, 1481â€"1489 (2011).
Scheidt-Nave, C. et al. Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause. J. Clin. Endocrinol. Metab. 86, 2032â€"2042 (2001).
Whitham, M. & Febbraio, M. A. The ever-expanding myokinome: discovery challenges and therapeutic implications. Nat. Rev. Drug Discov. 15, 719â€"729 (2016).
Tibble, C. A., Cavaiola, T. S. & Henry, R. R. Longer acting GLP-1 receptor agonists and the potential for improved cardiovascular outcomes: a review of current literature. Expert Rev. Endocrinol. Metab. 8, 247â€"259 (2013).
Glaesner, W. et al. Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab. Res. Rev. 26, 287â€"296 (2010).
Nauck, M. et al. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care 37, 2149â€"2158 (2014).
Larsson, L. et al. Sarcopenia: aging-related loss of muscle mass and function. Physiol. Rev. 99, 427â€"511 (2019).
Ma, C., Tonks, K. T., Center, J. R., Samocha-Bonet, D. & Greenfield, J. R. Complex interplay among adiposity, insulin resistance and bone health. Clin. Obes. 8, 131â€"139 (2018).
Xie, D. et al. Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass. Bone 40, 1352â€"1360 (2007).
Askmyr, M. et al. Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure. Sci. Rep. 5, 15529 (2015).
Hezareh, M., Hessell, A. J., Jensen, R. C., van de Winkel, J. G. & Parren, P. W. Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. J. Virol. 75, 12161â€"12168 (2001).
Schmittgen, T. D. & Livak, K. J. Analyzing real-time PCR data by the comparative C T method. Nat. Protocols 3, 1101â€"1108 (2008).
Chen, Z. P. et al. Effect of exercise intensity on skeletal muscle AMPK signaling in humans. Diabetes 52, 2205â€"2212 (2003).
Henstridge, D. C. et al. Genetic manipulation of cardiac Hsp72 levels does not alter substrate metabolism but reveals insights into high-fat feeding-induced cardiac insulin resistance. Cell Stress Chaperones 20, 461â€"472 (2015).
Jordy, A. B. et al. Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-fat diet-induced hepatosteatosis in mice. Am. J. Physiol. Endocrinol. Metab. 308, E778â€"E791 (2015).
Kowalski, G. M. et al. Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet. Biochim. Biophys. Acta 1851, 210â€"219 (2015).
Brandon, A. E. et al. Protein kinase C epsilon deletion in adipose tissue, but not in liver, improves glucose tolerance. Cell Metab. 29, 183â€"191.e7 (2019).
Hansotia, T. et al. Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes 53, 1326â€"1335 (2004).
Pal, M. et al. Alteration of JNK-1 signaling in skeletal muscle fails to affect glucose homeostasis and obesity-associated insulin resistance in mice. PLoS ONE 8, e54247 (2013).
