UCP1 in adipose tissues: two steps to full browning
- PMID: 28109720
- DOI: 10.1016/j.biochi.2017.01.007
UCP1 in adipose tissues: two steps to full browning
Abstract
The possibility that brown adipose tissue thermogenesis can be recruited in order to combat the development of obesity has led to a high interest in the identification of "browning agents", i.e. agents that increase the amount and activity of UCP1 in brown and brite/beige adipose tissues. However, functional analysis of the browning process yields confusingly different results when the analysis is performed in one of two alternative steps. Thus, in one of the steps, using cold acclimation as a potent model browning agent, we find that if the browning process is followed in mice initially housed at 21 °C (the most common procedure), there is only weak molecular evidence for increases in UCP1 gene expression or UCP1 protein abundance in classical brown adipose tissue; however, in brite/beige adipose depots, there are large increases, apparently associating functional browning with events only in the brite/beige tissues. Contrastingly, in another step, if the process is followed starting with mice initially housed at 30 °C (thermoneutrality for mice, thus similar to normal human conditions), large increases in UCP1 gene expression and UCP1 protein abundance are observed in the classical brown adipose tissue depots; there is then practically no observable UCP1 gene expression in brite/beige tissues. This apparent conundrum can be resolved when it is realized that the classical brown adipose tissue at 21 °C is already essentially fully differentiated and thus expands extensively through proliferation upon further browning induction, rather than by further enhancing cellular differentiation. When the limiting factor for thermogenesis, i.e. the total amount of UCP1 protein per depot, is analyzed, classical brown adipose tissue is by far the predominant site for the browning process, irrespective of which of the two steps is analyzed. There are to date no published data demonstrating that alternative browning agents would selectively promote brite/beige tissues versus classical brown tissue to a higher degree than does cold acclimation. Thus, to restrict investigations to examine adipose tissue depots where only a limited part of the adaptation process occurs (i.e. the brite/beige tissues) and to use initial conditions different from the thermoneutrality normally experienced by adult humans may seriously hamper the identification of therapeutically valid browning agents. The data presented here have therefore important implications for the analysis of the potential of browning agents and the nature of human brown adipose tissue.
Keywords: Beige; Brite; Browning; Cold acclimation; UCP1.
Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.
Similar articles
-
Understanding the Biology of Thermogenic Fat: Is Browning A New Approach to the Treatment of Obesity?Arch Med Res. 2017 Jul;48(5):401-413. doi: 10.1016/j.arcmed.2017.10.002. Arch Med Res. 2017. PMID: 29102386 Review.
-
UCP1 inhibition in Cidea-overexpressing mice is physiologically counteracted by brown adipose tissue hyperrecruitment.Am J Physiol Endocrinol Metab. 2017 Jan 1;312(1):E72-E87. doi: 10.1152/ajpendo.00284.2016. Epub 2016 Dec 6. Am J Physiol Endocrinol Metab. 2017. PMID: 27923808
-
Transcriptional regulation of the uncoupling protein-1 gene.Biochimie. 2017 Mar;134:86-92. doi: 10.1016/j.biochi.2016.09.017. Epub 2016 Oct 5. Biochimie. 2017. PMID: 27693079 Review.
-
Two key temporally distinguishable molecular and cellular components of white adipose tissue browning during cold acclimation.J Physiol. 2015 Aug 1;593(15):3267-80. doi: 10.1113/JP270805. Epub 2015 Jul 14. J Physiol. 2015. PMID: 26096127 Free PMC article.
-
UCP1 mRNA does not produce heat.Biochim Biophys Acta. 2013 May;1831(5):943-9. doi: 10.1016/j.bbalip.2013.01.009. Epub 2013 Jan 22. Biochim Biophys Acta. 2013. PMID: 23353596
Cited by
-
A comparative assessment of reference genes in mouse brown adipocyte differentiation and thermogenesis in vitro.Adipocyte. 2024 Dec;13(1):2330355. doi: 10.1080/21623945.2024.2330355. Epub 2024 Mar 25. Adipocyte. 2024. PMID: 38527945 Free PMC article.
-
Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning.NPJ Biofilms Microbiomes. 2024 Mar 13;10(1):22. doi: 10.1038/s41522-024-00495-8. NPJ Biofilms Microbiomes. 2024. PMID: 38480743 Free PMC article.
-
Dexamethasone Inhibits White Adipose Tissue Browning.Int J Mol Sci. 2024 Feb 27;25(5):2714. doi: 10.3390/ijms25052714. Int J Mol Sci. 2024. PMID: 38473960 Free PMC article.
-
Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.JCI Insight. 2024 Feb 22;9(4):e174097. doi: 10.1172/jci.insight.174097. JCI Insight. 2024. PMID: 38271099 Free PMC article.
-
Gut microbiota in overweight and obesity: crosstalk with adipose tissue.Nat Rev Gastroenterol Hepatol. 2024 Mar;21(3):164-183. doi: 10.1038/s41575-023-00867-z. Epub 2023 Dec 8. Nat Rev Gastroenterol Hepatol. 2024. PMID: 38066102 Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources