Adipose tissue-specific ablation of PGC-1 beta impairs thermogenesis in brown fat

0557788 - FGÚ 2023 RIV GB eng J - Journal Article
Funda, Jiří - Villena, J. A. - Bardová, Kristina - Adamcová, Kateřina - Irodenko, Ilaria - Flachs, Pavel - Jedličková, I. - Haasová, Eliška - Rossmeisl, Martin - Kopecký, Jan - Janovská, Petra
Adipose tissue-specific ablation of PGC-1 beta impairs thermogenesis in brown fat.
Disease Models & Mechanisms. Roč. 15, č. 4 (2022), č. článku dmm049223. ISSN 1754-8403. E-ISSN 1754-8411
R&D Projects: GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) EF16_013/0001775; GA ČR(CZ) GA18-04483S
Institutional support: RVO:67985823
Keywords : lipid metabolism * OPA1 * mice * adrenergic control
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 4.3, year: 2022
Method of publishing: Open access
https://doi.org/10.1242/dmm.049223

Impaired thermogenesis observed in mice with whole-body ablation of peroxisome proliferator-activated receptor-gamma coactivator-1 beta (PGC-1 beta, 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-1 beta knockout mice (PGC-1 beta-AT-KO mice) we aimed to learn whether specific PGC-1 beta ablation in adipocytes is sufficient to drive cold sensitivity. Indeed, we found that warm-adapted (30 degrees C) mutant mice were relatively sensitive to acute cold exposure (6 degrees 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-1 beta-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-1 beta-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-1 beta in controlling BAT lipid metabolism and thermogenesis.
Permanent Link: http://hdl.handle.net/11104/0331772