| First Author | Defour M | Year | 2018 |
| Journal | Mol Metab | Volume | 10 |
| Pages | 39-54 | PubMed ID | 29455954 |
| Mgi Jnum | J:327377 | Mgi Id | MGI:6791668 |
| Doi | 10.1016/j.molmet.2018.01.023 | Citation | Defour M, et al. (2018) The Peroxisome Proliferator-Activated Receptor alpha is dispensable for cold-induced adipose tissue browning in mice. Mol Metab 10:39-54 |
| abstractText | OBJECTIVE: Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue (BAT), a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARalpha) in cold-induced browning. Here we aimed to investigate the importance of PPARalpha in driving transcriptional changes during cold-induced browning in mice. METHODS: Male wildtype and PPARalpha-/- mice were housed at thermoneutrality (28 degrees C) or cold (5 degrees C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPARalpha-/- mice fasted for 24 h served as positive control for PPARalpha-dependent gene regulation. RESULTS: Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPARalpha-/- mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPARalpha genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPARalpha-/- mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPARalpha-/- mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid beta-oxidation to a similar extent in wildtype and PPARalpha-/- mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPARalpha-/- mice. Finally, pharmacological PPARalpha activation had a minimal effect on expression of cold-induced genes in murine WAT. CONCLUSION: Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPARalpha, indicating that PPARalpha is dispensable for cold-induced browning. |
