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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Galvao Valdivia, Luis Felipe ; Castro, Erique ; dos Santos Eichler, Rosangela Aparecida ; Moreno, Mayara Franzoi ; de Sousa, Erica ; Rodrigues Jardim, Giovanna Freitas ; Peixoto, Albert Souza ; Moraes, Maria Nathalia ; de Lauro Castrucci, Ana Maria ; Nedergaard, Jan ; Petrovic, Natasa ; Festuccia, William T. ; Reckziegel, Patricia

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 324, n. 4, p. 16-pg., 2023-04-01.

Abstract

Cold acclimation and pharmacological peroxisome proliferator-activated receptor y (PPARy) 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 PPARy agonism combined have addi-tive 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 degrees C or exposed to cold (7 degrees 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 PPARy 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 I33-adrenergic agonist CL316,243 and iBAT and iWAT respiration induced by succinate and pyruvate in compari-son 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 PPARy 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. NEW & NOTEWORTHY Cold acclimation and PPARy agonism combined markedly increase brown and white adipose tissue total UCP1 content and mRNA levels of thermogenesis-related proteins. Higher UCP1 protein levels did not result in higher energy ex-penditure. The high thermogenic capacity induced by PPARy agonism in cold-exposed animals markedly increases animals' body temperature in response to the I33-adrenergic agonist CL316,243. (AU)

• FAPESP's process: 17/26651-9 - Glaucoma as a model of temporal information disruption: impact on the metabolism
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