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Publication : Impact of leptin deficiency compared with neuronal-specific leptin receptor deletion on cardiometabolic regulation.

First Author  do Carmo JM Year  2019
Journal  Am J Physiol Regul Integr Comp Physiol Volume  317
Issue  4 Pages  R552-R562
PubMed ID  31411897 Mgi Jnum  J:280788
Mgi Id  MGI:6361825 Doi  10.1152/ajpregu.00077.2019
Citation  do Carmo JM, et al. (2019) Impact of leptin deficiency compared with neuronal-specific leptin receptor deletion on cardiometabolic regulation. Am J Physiol Regul Integr Comp Physiol 317(4):R552-R562
abstractText  The main goal of this study was to compare the impact of total body leptin deficiency with neuronal-specific leptin receptor (LR) deletion on metabolic and cardiovascular regulation. Liver fat, diacylglycerol acyltransferase-2 (DGTA2), and CD36 protein content were measured in wild-type (WT), nervous system LR-deficient (LR/Nestin-Cre), and leptin deficient (ob/ob) mice. Blood pressure (BP) and heart rate (HR) were recorded by telemetry, and motor activity (MA) and oxygen consumption (Vo2) were monitored at 24 wk of age. Female and male LR/Nestin-Cre and ob/ob mice were heavier than WT mice (62 +/- 5 and 61 +/- 3 vs. 31 +/- 1 g) and hyperphagic (6.2 +/- 0.5 and 6.1 +/- 0.7 vs. 3.5 +/- 1.0 g/day), with reduced Vo2 (27 +/- 1 and 33 +/- 1 vs 49 +/- 3 ml.kg(-1).min(-1)) and decreased MA (3 +/- 1 and 7 +/- 2 vs 676 +/- 105 cm/h). They were also hyperinsulinemic and hyperglycemic compared with WT mice. LR/Nestin-Cre mice had high levels of plasma leptin, while ob/ob mice had undetectable leptin levels. Despite comparable obesity, LR/Nestin-Cre mice had lower liver fat content, DGTA2, and CD36 protein levels than ob/ob mice. Male WT, LR/Nestin-Cre, and ob/ob mice exhibited similar BP (111 +/- 3, 110 +/- 1 and 109 +/- 2 mmHg). Female LR/Nestin-Cre and ob/ob mice, however, had higher BP than WT females despite similar metabolic phenotypes compared with male LR/Nestin-Cre and ob/ob mice. These results indicate that although nervous system LRs play a crucial role in regulating body weight and glucose homeostasis, peripheral LRs regulate liver fat deposition. In addition, our results suggest potential sex differences in the impact of obesity on BP regulation.
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