Atrial Natriuretic Peptide Orchestrates a Coordinated Physiological Response to Fuel Non-shivering Thermogenesis

Deborah Carper,Audrey Carrière,Carine Pestourie,Justine Vily Petit,Nathalie Viguerie,Marine Coué,Claire Laurens,Damien Lagarde,Frank Lezoualc’H,Maud Soty,Aline Mairal,Dominique Langin,Virginie Bourlier,Laurent Monbrun,Patrick Schrauwen,Arne Astrup,Louis Casteilla,Wouter Van Marken Lichtenbelt,Sébastien Déjean,Geneviève Tavernier,Valentin Barquissau,Yannick Jeanson,Gilles Mithieux,Wim H M Saris ,Emmani B M Nascimento ,Marie-Adeline Marquès ,Yannis Sainte–Marie ,Cédric Moro

doi:10.1016/j.celrep.2020.108075

Abstract

Atrial natriuretic peptide (ANP) is a cardiac hormone controlling blood volume and pressure in mammals. It is still unclear whether ANP controls cold-induced thermogenesis invivo. Here, we show that acute cold exposure induces cardiac ANP secretion in mice and humans. Genetic inactivation of ANP promotes cold intolerance and suppresses half of cold-induced brown adipose tissue (BAT) activation in mice. While white adipocytes are resistant to ANP-mediated lipolysis at thermoneutral temperature in mice, cold exposure renders white adipocytes fully responsive to ANP to activate lipolysis and a thermogenic program, a physiological response that is dramatically suppressed in ANP null mice. ANP deficiency also blunts liver triglycerides and glycogen metabolism, thus impairing fuel availability for BAT thermogenesis. ANP directly increases mitochondrial uncoupling and thermogenic gene expression in human white and brown adipocytes. Together, these results indicate that ANP is a major physiological trigger of BAT thermogenesis upon cold exposure in mammals.

Highlights

Warm-blooded animals have acquired the ability to maintain a constant core body temperature in fluctuating temperature environments through an adaptive physiological process called thermogenesis
Atrial natriuretic peptide (ANP) Is Required for Non-shivering Thermogenesis during Acute Cold Exposure [18F]Fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET/CT) imaging indicate that acute cold exposure at 4C for 5 h induces the recruitment of several brown adipose tissue (BAT) depots in the neck and clavicular areas in wildtype mice (Figures 1A and S1A)
BAT activation upon cold exposure was associated with a 3- to 4-fold increase of cardiac Nppa (ANP) expression (Figure 1B) and a 2-fold increase of plasma ANP (Figure 1C), while no change in cardiac Nppb (BNP) expression (Figure 1D) and plasma B-type NP (BNP) (Figure 1E) was observed

Summary

Introduction

Warm-blooded animals have acquired the ability to maintain a constant core body temperature in fluctuating temperature environments through an adaptive physiological process called thermogenesis. Brown adipose tissue (BAT) is considered the major site of non-shivering thermogenesis and heat production, which allows rodents to maintain euthermia at temperatures below thermoneutrality (Nedergaard and Cannon, 2010). Thermogenic genes can be readily induced in brown and beige adipocytes within white adipose tissue (WAT) in response to cold exposure (Cannon and Nedergaard, 2004; Harms and Seale, 2013; Wu et al, 2012). Thermogenic adipocytes consume a large amount of circulating triglycerides, glucose, and non-esterified fatty acid (NEFA) (Heine et al, 2018). BAT and WAT are innervated by sympathetic fibers (Jiang et al, 2017), which, upon cold exposure, release norepinephrine to acutely activate thermogenesis and lipolysis. In WAT, b3-adrenergic signaling activates adipocyte lipolysis through adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). WAT lipolysis is essential to provide fatty acid (FA) fuels in the fasting state to sustain high respiration rates in BAT (Schreiber et al, 2017; Shin et al, 2017)

Methods

Results

Discussion

Conclusion