Journal Article

Altered circadian feeding behavior and improvement of metabolic syndrome in obese Tac1-deficient mice

Kaiser, U B, Navarro, V M, León, S, Maguire, C A, Carroll, R S

2017

Overview

Background: Metabolic function is regulated by the interplay of central and peripheral factors that ultimately regulate food intake (FI) and energy expenditure. The tachykinin substance P (SP) has been identified as a novel regulator of energy balance, however, the mechanisms underlying this effect are ill-defined and conflicting data regarding the role of SP on FI have been reported by different groups. Objective: To further characterize the metabolic role of the Tac1 gene products (SP and neurokinin A) in mice through a series of genetic, metabolic and behavioral studies in Tac1 -deficient mice. Results: Tac1 −/− mice are leaner than controls and display reduced FI and altered feeding circadian rhythm, supported by disrupted expression of the clock genes Cry1 / 2 , Per1/2 in the suprachiasmatic nucleus, mediobasal hypothalamus (MBH) and liver, as well as increased proopiomelanocortin expression in the MBH. Tac1 ablation induced resistance to obesity, improved glucose tolerance, prevented insulin resistance under high-fat diet, increased activation of brown adipose tissue and improved hepatic steatosis. Moreover, deletion of Tac1 in ob/ob mice ameliorated body weight gain in females only but was sufficient to decrease fat and triglyceride content in the liver of males. Conclusions: These results provide further evidence that Tac1 controls circadian feeding behavior and metabolism in mice through mechanisms that involve the regulation of the melanocortin system. In addition, these studies suggest that the blockade of SP may offer a new method to treat metabolic syndrome.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38/22 / 631/378/1488/1562 / 64/60 / 692/163/2743/2037 / 96/63 / Ablation / Adipose tissue / Adipose tissue (brown) / Animal models / Animals / Body weight / Body weight gain / Care and treatment / Circadian Rhythm / Circadian rhythms / Complications and side effects / Cryptochromes / Development and progression / Disease Models, Animal / Energy balance / Energy expenditure / Energy Metabolism - drug effects / Epidemiology / Fatty liver / Feeding behavior / Feeding Behavior - drug effects / Food habits / Food intake / Gene expression / Genetic aspects / Genotypes / Glucose tolerance / Health aspects / Health Promotion and Disease Prevention / High fat diet / Hypothalamus / Insulin / Insulin resistance / Internal Medicine / Liver / Medicine / Medicine & Public Health / Melanocortin / Metabolic Diseases / Metabolic disorders / Metabolic syndrome / Metabolic Syndrome - drug therapy / Metabolic syndrome X / Mice / Mice, Knockout / Mice, Obese / Neurokinin / Neurokinin A / Neurokinin-1 Receptor Antagonists - pharmacology / Obesity / original-article / Period 1 protein / Physiological aspects / Proopiomelanocortin / Public Health / Receptors, Neurokinin-1 - drug effects / Risk factors / Rodents / Signal Transduction / Steatosis / Substance P / Substance P - pharmacology / Suprachiasmatic nucleus / Tachykinin / Tachykinins - deficiency / Triglycerides