Leptin Engages a Hypothalamic Neurocircuitry to Permit Survival in the Absence of Insulin

Teppei Fujikawa, Eric D. Berglund, Vishal R. Patel, Giorgio Ramadori, Claudia R. Vianna, Linh Vong, Fabrizio Thorel, Simona Chera, Pedro L. Herrera, Bradford B. Lowell, Joel K. Elmquist, Pierre Baldi, Roberto Coppari

Research output: Contribution to journalArticle

72 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)431-444
Number of pages14
JournalCell Metabolism
Volume18
Issue number3
DOIs
StatePublished - Sep 3 2013

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Fujikawa, T., Berglund, E. D., Patel, V. R., Ramadori, G., Vianna, C. R., Vong, L., Thorel, F., Chera, S., Herrera, P. L., Lowell, B. B., Elmquist, J. K., Baldi, P., & Coppari, R. (2013). Leptin Engages a Hypothalamic Neurocircuitry to Permit Survival in the Absence of Insulin. Cell Metabolism, 18(3), 431-444. https://doi.org/10.1016/j.cmet.2013.08.004