| First Author | Senn SS | Year | 2019 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 317 |
| Issue | 3 | Pages | R451-R460 |
| PubMed ID | 31314542 | Mgi Jnum | J:279262 |
| Mgi Id | MGI:6360419 | Doi | 10.1152/ajpregu.00111.2019 |
| Citation | Senn SS, et al. (2019) Unsilencing of native LepRs in hypothalamic SF1 neurons does not rescue obese phenotype in LepR-deficient mice. Am J Physiol Regul Integr Comp Physiol 317(3):R451-R460 |
| abstractText | 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 (LepR(loxTB)) mice with 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. LepR(loxTB) x SF1-Cre [knockout (KO)/Tg+] mice were metabolically phenotyped and compared with littermate controls that either expressed or were deficient in LepRs. Leptin-induced phosphorylated STAT3 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 with KO/Tg+ mice, nor did KO/Tg+ mice show improved glucose tolerance. The presence of functional LepRs in the VMH mildly enhanced sensitivity to the pancreatic hormone amylin. When maintained on a high-fat diet (HFD), there was no reduction in diet-induced obesity in KO/Tg+ mice, but KO/Tg+ mice had improved glucose tolerance after 7 wk on an HFD compared with LepR-null mice. We conclude that LepR signaling in the VMH alone is not sufficient to correct metabolic dysfunction observed in LepR-null mice. |
