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POMC neurons expressing leptin receptors coordinate metabolic responses to fasting via suppression of leptin levels.
Caron, Alexandre; Dungan Lemko, Heather M; Castorena, Carlos M; Fujikawa, Teppei; Lee, Syann; Lord, Caleb C; Ahmed, Newaz; Lee, Charlotte E; Holland, William L; Liu, Chen; Elmquist, Joel K.
Afiliación
  • Caron A; Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
  • Dungan Lemko HM; Howard Community College, Columbia, United States.
  • Castorena CM; Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
  • Fujikawa T; Department of Cellular and Integrative Physiology, UT Health San Antonio, San Antonio, United States.
  • Lee S; Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
  • Lord CC; Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
  • Ahmed N; Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
  • Lee CE; Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
  • Holland WL; Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
  • Liu C; Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
  • Elmquist JK; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States.
Elife ; 72018 03 12.
Article en En | MEDLINE | ID: mdl-29528284
Leptin is critical for energy balance, glucose homeostasis, and for metabolic and neuroendocrine adaptations to starvation. A prevalent model predicts that leptin's actions are mediated through pro-opiomelanocortin (POMC) neurons that express leptin receptors (LEPRs). However, previous studies have used prenatal genetic manipulations, which may be subject to developmental compensation. Here, we tested the direct contribution of POMC neurons expressing LEPRs in regulating energy balance, glucose homeostasis and leptin secretion during fasting using a spatiotemporally controlled Lepr expression mouse model. We report a dissociation between leptin's effects on glucose homeostasis versus energy balance in POMC neurons. We show that these neurons are dispensable for regulating food intake, but are required for coordinating hepatic glucose production and for the fasting-induced fall in leptin levels, independent of changes in fat mass. We also identify a role for sympathetic nervous system regulation of the inhibitory adrenergic receptor (ADRA2A) in regulating leptin production. Collectively, our findings highlight a previously unrecognized role of POMC neurons in regulating leptin levels.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proopiomelanocortina / Receptores Adrenérgicos alfa 2 / Leptina / Neuronas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Elife Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proopiomelanocortina / Receptores Adrenérgicos alfa 2 / Leptina / Neuronas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Elife Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido