Impact of leptin deficiency compared with neuronal-specific leptin receptor deletion on cardiometabolic regulation
| Autor: | Xuemei Dai, Alexandre A. da Silva, F. N. Gava, Jussara M. do Carmo, John E. Hall, Sydney P. Moak |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Blood Glucose CD36 Antigens Leptin Male medicine.medical_specialty Adrenergic Antagonists Physiology media_common.quotation_subject Mice Obese Blood Pressure 030204 cardiovascular system & hematology Body weight 03 medical and health sciences Angiotensin Receptor Antagonists Mice 0302 clinical medicine Heart Rate Stress Physiological Physiology (medical) Internal medicine Liver fat medicine Animals Diacylglycerol O-Acyltransferase Aldosterone media_common Mineralocorticoid Receptor Antagonists Mice Knockout Leptin Deficiency Leptin receptor business.industry Fatty liver Appetite Total body medicine.disease Receptors Adrenergic 030104 developmental biology Blood pressure Endocrinology Adipose Tissue Gene Expression Regulation Receptors Leptin Female business Research Article |
| Zdroj: | Am J Physiol Regul Integr Comp Physiol |
| ISSN: | 1522-1490 |
| Popis: | 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 (V̇o2) 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 V̇o2 (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. |
| Databáze: | OpenAIRE |
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