Monday, October 25, 2021
Cold Thermogenesis

RCMI 2021 | 11.03.01 – Lucia Seale


Authors :: LA Seale, AM Zavacki, MJ Berry ¬— Pacific Biosciences Research Center, School of Ocean and Earth Science Technology, University of Hawaii at Manoa, Honolulu, HI AND Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

PURPOSE: Brown adipose tissue (BAT) is the main site of adaptive thermogenesis (AT), a mechanism for heat production triggered by exposure to cold or after caloric overload that allows for mammalian energy expenditure control and thermoregulation. Impairment of AT contributes to obesity development in humans. AT is primarily carried out by uncoupling protein 1, a mitochondrial proton pump that converts chemical energy into heat. The contribution of micronutrients in AT is poorly understood, particularly of selenium (Se). Se participates in strong redox reactions via its presence in selenoproteins, i.e., proteins that contain Se in their primary structure as the amino acid selenocysteine (Sec). Selenoproteins act on redox reactions, curbing oxidative stress and activating thyroid hormone, which controls energy homeostasis. Despite several studies associating Se and energy metabolism, the role of dietary Se in BAT is poorly understood. We previously developed a mouse model lacking the Se recycling enzyme Sec lyase (Scly) in which obesity developed after a Se-deficient diet in a sexually dimorphic manner, with male mice presenting a more pronounced phenotype. We used this mouse model to investigate the role of dietary Se in BAT AT. METHODS: BAT from Scly KO mice fed low (0.08 ppm) or adequate (0.25 ppm) selenite diets were assessed for Se content, morphology, and expression of selenoproteins. Mice were also exposed to 4 ºC, and core body temperature, oxygen consumption, and carbon dioxide production evaluated. RESULTS: BAT of Scly KO mice were larger and had lower Se content than wild-type counterparts, with reduced expression of selenoproteins Dio2, SelenoW and Gpx1. Se-deficient Scly KO mice reduced their body temperature, oxygen consumption, and carbon dioxide production after cold exposure. CONCLUSION: Diminished BAT Se levels compromise cold-induced AT mechanisms reducing energy expenditure and selenoproteins, contributing to obesity development in mice without Se recycling.

Grant Support :: Partial funding from the National Institutes of Health (grants R01DK047320-24S1, R01DK047320-22S2, U54MD007601 Ola Hawaii – subproject 5544); Hawaii Community Foundation (20ADVC-102166,) and start-up funds. The content is solely the authors’ responsibility and does not necessarily represent the official views of funding agencies.


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