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Cold acclimation and pioglitazone combined increase thermogenic capacity of brown and white adipose tissues but this does not translate into higher energy expenditure in mice
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Number of Authors: 132023 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 324, no 4, p. E358-E373Article in journal (Refereed) Published
Abstract [en]

Cold acclimation and pharmacological peroxisome proliferator-activated receptor γ (PPARγ) activation have each earlier been shown to recruit brown adipose tissue (BAT) and beige adipocytes thermogenic machinery, enhancing uncoupling protein 1 (UCP1)-mediated thermogenic capacity. We here investigated whether cold acclimation and PPARγ agonism combined have additive effects in inducing brown and beige adipocytes UCP1 content and whether this translates into a higher thermogenic capacity and energy expenditure. C57BL/6J mice treated or not with pioglitazone (30 mg/kg/day) were maintained at 21°C or exposed to cold (7°C) for 15 days and evaluated for thermogenic capacity, energy expenditure and interscapular BAT (iBAT) and inguinal white adipose tissue (iWAT) mass, morphology, UCP1 content and gene expression, glucose uptake and oxygen consumption. Cold acclimation and PPARγ agonism combined synergistically increased iBAT and iWAT total UCP1 content and mRNA levels of the thermogenesis-related proteins PGC1a, CIDEA, FABP4, GYK, PPARa, LPL, GLUTs (GLUT1 in iBAT and GLUT4 in iWAT), and ATG when compared to cold and pioglitazone individually. This translated into a stronger increase in body temperature in response to the β3-adrenergic agonist CL316,243 and iBAT and iWAT respiration induced by succinate and pyruvate in comparison to that seen in either cold-acclimated or pioglitazone-treated mice. However, basal energy expenditure, BAT glucose uptake and glucose tolerance were not increased above that seen in cold-acclimated untreated mice. In conclusion, cold acclimation and PPARγ agonism combined induced a robust increase in brown and beige adipocytes UCP1 content and thermogenic capacity, much higher than each treatment individually. However, our findings enforce the concept that increases in total UCP1 do not innately lead to higher energy expenditure.

Place, publisher, year, edition, pages
2023. Vol. 324, no 4, p. E358-E373
Keywords [en]
adipogenesis, browning, pioglitazone, thermogenesis, UCP1
National Category
Physiology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-216979DOI: 10.1152/ajpendo.00217.2022ISI: 000974585600001PubMedID: 36856189Scopus ID: 2-s2.0-85152170431OAI: oai:DiVA.org:su-216979DiVA, id: diva2:1755814
Available from: 2023-05-09 Created: 2023-05-09 Last updated: 2023-05-09Bibliographically approved

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Nedergaard, JanPetrovic, Natasa

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Nedergaard, JanPetrovic, Natasa
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Department of Molecular Biosciences, The Wenner-Gren Institute
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