Cold exposure drives weight gain and adiposity following chronic suppression of brown adipose tissue

Aldiss, P., Lewis, J.E., Lupini, I., Bloor, I., Chavoshinejad, R., Boocock, D. ORCID: 0000-0002-7333-3549, Miles, A.K., Ebling, F.J.P., Budge, H. and Symonds, M.E., 2022. Cold exposure drives weight gain and adiposity following chronic suppression of brown adipose tissue. International Journal of Molecular Sciences, 23 (3): 1869. ISSN 1661-6596

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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 and β3-adrenoreceptor agonism 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 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.

Item Type: Journal article
Publication Title: International Journal of Molecular Sciences
Creators: Aldiss, P., Lewis, J.E., Lupini, I., Bloor, I., Chavoshinejad, R., Boocock, D., Miles, A.K., Ebling, F.J.P., Budge, H. and Symonds, M.E.
Publisher: MDPI
Date: 7 February 2022
Volume: 23
Number: 3
ISSN: 1661-6596
Identifiers:
NumberType
10.3390/ijms23031869DOI
1510277Other
Divisions: Schools > School of Science and Technology
Record created by: Jeremy Silvester
Date Added: 28 Jan 2022 15:22
Last Modified: 10 Feb 2022 08:52
Related URLs:
URI: http://irep.ntu.ac.uk/id/eprint/45441

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