Impaired thermogenesis observed in mice with whole-body ablation of peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β; officially known as PPARGC1B) may result from impaired brown fat (brown adipose tissue; BAT) function, but other mechanism(s) could be involved. Here, using adipose-specific PGC-1β knockout mice (PGC-1β-AT-KO mice) we aimed to learn whether specific PGC-1β ablation in adipocytes is sufficient to drive cold sensitivity. Indeed, we found that warm-adapted (30°C) mutant mice were relatively sensitive to acute cold exposure (6°C). When these mice were subjected to cold exposure for 7 days (7-day-CE), adrenergic stimulation of their metabolism was impaired, despite similar levels of thermogenic uncoupling protein 1 in BAT in PGC-1β-AT-KO and wild-type mice. Gene expression in BAT of mutant mice suggested a compensatory increase in lipid metabolism to counteract the thermogenic defect. Interestingly, a reduced number of contacts between mitochondria and lipid droplets associated with low levels of L-form of optic atrophy 1 was found in BAT of PGC-1β-AT-KO mice. These genotypic differences were observed in warm-adapted mutant mice, but they were partially masked by 7-day-CE. Collectively, our results suggest a role for PGC-1β in controlling BAT lipid metabolism and thermogenesis. This article has an associated First Person interview with the first author of the paper.

Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas Instituto de Salud Carlos 3 28029 Madrid Spain

Department of Physiology Faculty of Science Charles University Prague 128 44 Prague Czech Republic

Laboratory of Adipose Tissue Biology Institute of Physiology of the Czech Academy of Sciences 142 20 Prague Czech Republic

Laboratory of Metabolism and Obesity Vall d'Hebron Institut de Recerca Universitat Autònoma de Barcelona 08035 Barcelona Spain

Research Unit for Rare Diseases Department of Paediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital 128 08 Prague Czech Republic

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