Impact of leptin deficiency compared to neuronal specific leptin receptor deletion on cardiometabolic regulation.

08:00 EDT 14th August 2019 | BioPortfolio

Summary of "Impact of leptin deficiency compared to neuronal specific leptin receptor deletion on cardiometabolic regulation."

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 (VO) were monitored at 24 weeks 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), hyperphagic (6.2±0.5 and 6.1±0.7 vs 3.5±1.0 g/day), with reduced VO (27±1 and 33±1 vs 49±3 ml/kg/min) and decreased MA (3±1 and 7±2 vs 676±105 cm/hr). They were also hyperinsulinemic, and hyperglycemic compared to 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 and109±2 mmHg). Female LR/Nestin-Cre and ob/ob mice, however, had higher BP than WT females despite similar metabolic phenotypes compared to 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.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Regulatory, integrative and comparative physiology
ISSN: 1522-1490


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Medical and Biotech [MESH] Definitions

Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.

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A suppressor of cytokine signaling protein that consists of an N-terminal kinase-inhibitory region, a central SH2 DOMAIN, a characteristic C-terminal SOCS box (a 40-amino acid motif, which functions to recruit E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES). SOCS3 inhibits cytokine signaling by binding to RECEPTOR PROTEIN-TYROSINE KINASES as well as CYTOKINE RECEPTOR GP130; ERYTHROPOIETIN RECEPTORS; INSULIN RECEPTOR; and the LEPTIN RECEPTOR. Its functions include suppression of ERYTHROPOIESIS in the fetal liver.

Polypeptides produced by the ADIPOCYTES. They include LEPTIN; ADIPONECTIN; RESISTIN; and many cytokines of the immune system, such as TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-6; and COMPLEMENT FACTOR D (also known as ADIPSIN). They have potent autocrine, paracrine, and endocrine functions.

A specific subtype of muscarinic receptor that has a high affinity for the drug PIRENZEPINE. It is found in the peripheral GANGLIA where it signals a variety of physiological functions such as GASTRIC ACID secretion and BRONCHOCONSTRICTION. This subtype of muscarinic receptor is also found in neuronal tissues including the CEREBRAL CORTEX and HIPPOCAMPUS where it mediates the process of MEMORY and LEARNING.

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