Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta.

Patricia Pazos,Luis Lima,Carlos Diéguez,María C García

doi:10.1155/2014/537603

Abstract

The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6), a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY) and agouti-related peptide (AgRP) and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART). Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18) were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice) on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta.

Highlights

Energy homeostasis, defined as the process whereby body weight and energy reserves are maintained stable over long periods of time, is tightly regulated through the complex interactions of the brain and peripheral organs [1, 2]
Afferent endocrine signals projecting to the brain to encode short- and long-term energy status comprise a wide variety of tissue-specific signalling molecules including: (i) adipokines (e.g., leptin, adiponectin, resistin, and interleukin-6 (IL-6)), secreted by the expanding adipose tissue; (ii) pancreatic hormones such as insulin and amylin; (iii) gastrointestinal peptides, such as ghrelin, glucagon-like peptide I, and peptide YY; and (iv) gonadal and placental hormones, such as steroids and placental lactogens [2, 6,7,8]
The other produces cocaine and amphetamine regulated transcript (CART) and proopiomelanocortin- (POMC-) derived peptides, such as alpha melanocyte stimulating hormone, that promote anorexia by inhibiting food intake and increases catabolic processes. αMSH modulates its downstream homeostatic signalling via their action at melanocortin receptors MC3R and MC4R, which are antagonized by agouti-related peptide (AgRP) [2]

Summary

Introduction

Energy homeostasis, defined as the process whereby body weight and energy reserves are maintained stable over long periods of time, is tightly regulated through the complex interactions of the brain and peripheral organs [1, 2]. Reciprocal neural networks within the hypothalamus and the brain stem act in response to peripheral (metabolic, endocrine, and neural) signals of metabolic status, matching energy intake with energy outputs such as basal metabolism, activity, thermogenesis, and reproduction [3,4,5]. Several hypothalamic neuronal populations express specific receptors for these metabolic hormones and communicate within each other via chemical synapses and the release of neurotransmitters and neuropeptides, characterized by having either direct or indirect effects on body weight regulation and reproductive function [9]. The coordinated regulation of these neurons and their efferent projections to key brain regions such as the paraventricular nucleus (PVN) and the medial preoptic and lateral hypothalamic area (LH) contributes to regulate energy metabolism, gonadotropin-releasing hormone (GnRH) release, and pituitary-gonadal axis activity [2, 10, 11]

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