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Review
. 2020 Aug 28;21(17):6241.
doi: 10.3390/ijms21176241.

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Alina Kuryłowicz  1 , Monika Puzianowska-Kuźnicka  1   2
Affiliations
Review

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Alina Kuryłowicz et al. Int J Mol Sci. .

Abstract

The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies to restore the energy balance. Therefore, the concept of activating brown adipose tissue (BAT) in order to increase energy expenditure has been revived. In mammals, two developmentally distinct types of brown adipocytes exist; the classical or constitutive BAT that arises during embryogenesis, and the beige adipose tissue that is recruited postnatally within white adipose tissue (WAT) in the process called browning. Research of recent years has significantly increased our understanding of the mechanisms involved in BAT activation and WAT browning. They also allowed for the identification of critical molecules and critical steps of both processes and, therefore, many new therapeutic targets. Several non-pharmacological approaches, as well as chemical compounds aiming at the induction of WAT browning and BAT activation, have been tested in vitro as well as in animal models of genetically determined and/or diet-induced obesity. The therapeutic potential of some of these strategies has also been tested in humans. In this review, we summarize present concepts regarding potential therapeutic targets in the process of BAT activation and WAT browning and available strategies aiming at them.

Keywords: beige adipocyte; brown adipocyte; obesity; thermogenesis; white adipose tissue browning.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Selected molecular mechanisms involved in white adipose tissue browning and brown adipose tissue activation that could constitute potential therapeutic targets for obesity treatment. Stimulation of adrenergic receptors β3 (ADRB3) is crucial for the initiation of thermogenic pathways, leading to the induction of proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC-1α) and PPARγ. Sirtuin 1 (SIRT1) also activates PPARγ and enables the recruitment of PRDM16 (PR domain containing 16) transcription factor and initiation of the brown fat specific program. These mechanisms regulate the differentiation of beige progenitors toward mature beige adipocytes and the transdifferentiation of white to beige adipocytes. Stimuli activating ADRB3 and SIRT1 are also involved in brown adipocyte differentiation, proliferation, and activation leading to the change from the low-thermogenic toward the high-thermogenic phenotype.
See this image and copyright information in PMC

References

    1. Schulz T.J., Tseng Y.H. Brown adipose tissue: Development, metabolism and beyond. Biochem. J. 2013;453:167–178. doi: 10.1042/BJ20130457. - DOI - PMC - PubMed
    1. Petrovic N., Walden T.B., Shabalina I.G., Timmons J.A., Cannon B., Nedergaard J. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J. Biol. Chem. 2010;285:7153–7164. - PMC - PubMed
    1. Guerra C., Koza R.A., Yamashita H., Walsh K., Kozak L.P. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J. Clin. Investig. 1998;102:412–420. doi: 10.1172/JCI3155. - DOI - PMC - PubMed
    1. Almind K., Manieri M., Sivitz W.I., Cinti S., Kahn C.R. Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice. Proc. Natl. Acad. Sci. USA. 2007;104:2366–2371. doi: 10.1073/pnas.0610416104. - DOI - PMC - PubMed
    1. Spaethling J.M., Sanchez-Alavez M., Lee J., Xia F.C., Dueck H., Wang W., Fisher S.A., Sul J.Y., Seale P., Kim J., et al. Single-cell transcriptomics and functional target validation of brown adipocytes show their complex roles in metabolic homeostasis. FASEB J. 2016;30:81–92. doi: 10.1096/fj.15-273797. - DOI - PubMed