Leptin Receptor Signaling in Sim1-Expressing Neurons Regulates Body Temperature and Adaptive Thermogenesis

Endocrinology
Isin CakirMasoud Ghamari-Langroudi

Abstract

Leptin signals to regulate food intake and energy expenditure under conditions of normative energy homeostasis. The central expression and function of leptin receptor B (LepRb) have been extensively studied during the past two decades; however, the mechanisms by which LepRb signaling dysregulation contributes to the pathophysiology of obesity remains unclear. The paraventricular nucleus of the hypothalamus (PVN) plays a crucial role in regulating energy balance as well as the neuroendocrine axes. The role of LepRb expression in the PVN in regard to the regulation of physiological function of leptin has been controversial. The single-minded homolog 1 gene (Sim1) is densely expressed in the PVN and in parts of the amygdala, making Sim1-Cre mice a useful model for examining molecular mechanisms regulating PVN function. In this study, we characterized the physiological role of LepRb in Sim1-expressing neurons using LepRb-floxed × Sim1-Cre mice. Sim1-specific LepRb-deficient mice were surprisingly hypophagic on regular chow but gained more weight upon exposure to a high-fat diet than did their control littermates. We show that Sim1-specific deletion of a single LepRb gene copy caused decreased surface and core body temperatures as w...Continue Reading

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Citations

Oct 1, 2019·Hypertension·Snigdha MukerjeeEric Lazartigues
Feb 20, 2020·Nutrients·Patricia Seoane-CollazoCristina Contreras
Dec 18, 2019·Journal of Physiology and Biochemistry·Ismael González-GarcíaCristina Contreras
Nov 6, 2020·Endocrine Reviews·Sandra PereiraTimothy J Kieffer
Jul 3, 2021·International Journal of Molecular Sciences·Valentina Annamaria GenchiSebastio Perrini

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