@article{bf7afb4ed3d0401da943c20006a5ae1c,
title = "Leptin Engages a Hypothalamic Neurocircuitry to Permit Survival in the Absence of Insulin",
abstract = "Summary The dogma that life without insulin is incompatible has recently been challenged by results showing the viability of insulin-deficient rodents undergoing leptin monotherapy. Yet, the mechanisms underlying these actions of leptin are unknown. Here, the metabolic outcomes of intracerebroventricular (i.c.v.) administration of leptin in mice devoid of insulin and lacking or re-expressing leptin receptors (LEPRs) only in selected neuronal groups were assessed. Our results demonstrate that concomitant re-expression of LEPRs only in hypothalamic γ-aminobutyric acid (GABA) and pro-opiomelanocortin (POMC) neurons is sufficient to fully mediate the lifesaving and antidiabetic actions of leptin in insulin deficiency. Our analyses indicate that enhanced glucose uptake by brown adipose tissue and soleus muscle, as well as improved hepatic metabolism, underlies these effects of leptin. Collectively, our data elucidate a hypothalamic-dependent pathway enabling life without insulin and hence pave the way for developing better treatments for diseases of insulin deficiency.",
author = "Teppei Fujikawa and Berglund, {Eric D.} and Patel, {Vishal R.} and Giorgio Ramadori and Vianna, {Claudia R.} and Linh Vong and Fabrizio Thorel and Simona Chera and Herrera, {Pedro L.} and Lowell, {Bradford B.} and Elmquist, {Joel K.} and Pierre Baldi and Roberto Coppari",
note = "Funding Information: We thank Drs. Mirco Gallie and Kim Ki Woo for providing technical advice; Massimo Attanasio, Claes Wollheim, Christian Bj{\o}rb{\ae}k, and Paolo Sassone-Corsi for critical reading of the manuscript; and Joyce Repa for providing some of the quantitative real-time PCR primers. This work was supported by the Juvenile Diabetes Research Foundation (postdoctoral fellowship 3-2011-405 to T.F.), the American Heart Association (postdoctoral fellowship to G.R. and Scientist Development Grant to R.C.), the National Science Foundation (NSFIIS-0513376 to P.B.), and National Institutes of Health Grants (FDK092083A to E.D.B.; F32 DK078478 to L.V; R01 DK089044, R01 DK075632, P30 DK046200, and P30DK057521 to B.B.L.; RL1 DK081185 and R37 DK053301 to J.K.E.; LM010235 and NLM T15LM07443 to P.B.; and R01 DK080836 and R01 DK091680 to R.C.). This work has also received the unrestricted support of the Louis-Jeantet Foundation (to R.C.). ",
year = "2013",
month = sep,
day = "3",
doi = "10.1016/j.cmet.2013.08.004",
language = "English (US)",
volume = "18",
pages = "431--444",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}