Unsilencing of native leptin receptors (LepR) in hypothalamic SF1 neurons does not rescue obese phenotype in LepR-deficient mice.

Unsilencing of native leptin receptors (LepR) in hypothalamic SF1 neurons does not rescue obese phenotype in LepR-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2019 Jul 17;: Authors: Senn SS, Le Foll C, Whiting L, Tarasco E, Duffy S, Lutz TA, Boyle CN Abstract Leptin receptor (LepR) signaling in neurons of the ventromedial nucleus of the hypothalamus (VMH), specifically those expressing steroidogenic factor-1 (SF1), have been proposed to play a key role in controlling energy balance. By crossing LepR-silenced (LepRloxTB) mice to those expressing SF1-Cre, we unsilenced native LepR specifically in the VMH and tested whether SF1 neurons in the VMH are critical mediators of leptin's effect on energy homeostasis. LepRloxTB x SF1-Cre (KO/Tg+) mice were metabolically phenotyped and compared to littermate controls that either expressed or were deficient in LepR. Leptin-induced pSTAT3 was present in the VMH of KO/Tg+ mice and absent in other hypothalamic nuclei. VMH leptin signaling did not ameliorate obesity resulting from LepR-deficiency in chow-fed mice. There was no change in food intake or energy expenditure when comparing complete LepR-null mice to KO/Tg+ mice, nor did KO/Tg+ show improved glucose tolerance. The presence of functional LepR in the VMH mildly enhanced sensitivity to the pancreatic hormone amylin. When maintained on high fat diet (HFD), there was no reduction in diet-induced obesity in KO/Tg+ mice, but KO/Tg+ mic...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research