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Miao Y, Warner M, Gustafsson JK. Liver X receptor β: new player in the regulatory network of thyroid hormone and 'browning' of white fat. Adipocyte. 2016;5(2):238-42doi: 10.1080/21623945.2016.1142634.
Miao, Y., Warner, M., & Gustafsson, J. K. (2016). Liver X receptor β: new player in the regulatory network of thyroid hormone and 'browning' of white fat. Adipocyte, 5(2), 238-42. https://doi.org/10.1080/21623945.2016.1142634
Miao, Yifei, et al. "Liver X receptor β: new player in the regulatory network of thyroid hormone and 'browning' of white fat." Adipocyte vol. 5,2 (2016): 238-42. doi: https://doi.org/10.1080/21623945.2016.1142634
Miao Y, Warner M, Gustafsson JK. Liver X receptor β: new player in the regulatory network of thyroid hormone and 'browning' of white fat. Adipocyte. 2016 Mar 17;5(2):238-42. doi: 10.1080/21623945.2016.1142634. eCollection 2016. PMID: 27386163; PMCID: PMC4916863.
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Adipocyte. 2016 Mar 17;5(2):238-42. doi: 10.1080/21623945.2016.1142634. eCollection 2016.

Liver X receptor β: new player in the regulatory network of thyroid hormone and 'browning' of white fat.

Adipocyte

Yifei Miao, Margaret Warner, Jan-Ke Gustafsson

Affiliations

  1. Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston , Houston, TX, USA.
  2. Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA; Center for Medical Innovations, Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Stockholm, Sweden.

PMID: 27386163 PMCID: PMC4916863 DOI: 10.1080/21623945.2016.1142634

Abstract

The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type II diabetes. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride and glucose metabolism. Following our previous finding that LXRs serve as repressors of UCP1 in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyrotropin releasing hormone positive neurons in the paraventricular area of the hypothalamus, and thus stimulated secretion of thyroid-stimulating hormone from the pituitary. Consequently production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. One unexpected finding of our study is that LXRs are indispensable in the thyroid hormone negative feedback loop at the level of the hypothalamus. LXRs maintain expression of thyroid receptors in the brain and when they are inactivated there is no negative feedback of thyroid hormone in the hypothalamus. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knock-out mice and provided support for targeting LXRs in treatment of obesity.

Keywords: HPT axis; UCP1; beige cells; browning of adipose tissue; liver X receptors; negative feedback loop; thyroid hormones

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