Cold Exposure Drives Weight Gain and Adiposity following Chronic Suppression of Brown Adipose Tissue

Peter Aldiss*, Jo E. Lewis, Irene Lupini, Ian Bloor, Ramyar Chavoshinejad, David J. Boocock, Amanda K. Miles, Francis J.P. Ebling, Helen Budge, Michael E. Symonds

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

2 Citationer (Scopus)
24 Downloads (Pure)

Abstract

Therapeutic activation of thermogenic brown adipose tissue (BAT) may be feasible to prevent, or treat, cardiometabolic disease. However, rodents are commonly housed below thermoneutrality (~20 °C) which can modulate their metabolism and physiology including the hyperactivation of brown (BAT) and beige white adipose tissue. We housed animals at thermoneutrality from weaning to chronically supress BAT, mimic human physiology and explore the efficacy of chronic, mild cold exposure (20 °C) and β3-adrenoreceptor agonism (YM-178) under these conditions. Using metabolic phenotyping and exploratory proteomics we show that transfer from 28 °C to 20 °C drives weight gain and a 125% increase in subcutaneous fat mass, an effect not seen with YM-178 administration, thus suggesting a direct effect of a cool ambient temperature in promoting weight gain and further adiposity in obese rats. Following chronic suppression of BAT, uncoupling protein 1 mRNA was undetectable in the subcutaneous inguinal white adipose tissue (IWAT) in all groups. Using exploratory adipose tissue proteomics, we reveal novel gene ontology terms associated with cold-induced weight gain in BAT and IWAT whilst Reactome pathway analysis highlights the regulation of mitotic (i.e., G2/M transition) and metabolism of amino acids and derivatives pathways. Conversely, YM-178 had minimal metabolic-related effects but modified pathways involved in proteolysis  i.e., eukaryotic translation initiation) and RNA surveillance across both tissues. Taken together these findings are indicative of a novel mechanism whereby animals increase body weight and fat mass following chronic suppression of adaptive thermogenesis from weaning. In addition, treatment with a B3-adrenoreceptor agonist did not improve metabolic health in obese animals raised at thermoneutrality.

OriginalsprogEngelsk
Artikelnummer1869
TidsskriftInternational Journal of Molecular Sciences
Vol/bind23
Udgave nummer3
Antal sider16
ISSN1661-6596
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Funding: This research was funded by The British Heart Foundation, grant number FS/15/4/31184/] and the APC was funded by the University of Nottingham/British Heart Foundation

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Citationsformater