Regulator of Calcineurin 1 helps coordinate whole-body metabolism and thermogenesis

David Rotter, Heshan Peiris, D Grinsfelder, Alyce Martin, Jana Burchfield, Valentina Parra, Christi Hull, Cyndi Morales, Claire Jessup, Dusan Matusica, Brian Parks, Aldons Lusis, Ngoc Nguyen, Misook Oh, Israel Iyoke, Tanvi Jakkampudi, D McMillan, Hesham Sadek, Matthew Watt, Rana GuptaMelanie Pritchard, Damien Keating, Beverly Rothermel

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Increasing non-shivering thermogenesis (NST), which expends calories as heat rather than storing them as fat, is championed as an effective way to combat obesity and metabolic disease. Innate mechanisms constraining the capacity for NST present a fundamental limitation to this approach, yet are not well understood. Here, we provide evidence that Regulator of Calcineurin 1 (RCAN1), a feedback inhibitor of the calcium-activated protein phosphatase calcineurin (CN), acts to suppress two distinctly different mechanisms of non-shivering thermogenesis (NST): one involving the activation of UCP1 expression in white adipose tissue, the other mediated by sarcolipin (SLN) in skeletal muscle. UCP1 generates heat at the expense of reducing ATP production, whereas SLN increases ATP consumption to generate heat. Gene expression profiles demonstrate a high correlation between Rcan1 expression and metabolic syndrome. On an evolutionary timescale, in the context of limited food resources, systemic suppression of prolonged NST by RCAN1 might have been beneficial; however, in the face of caloric abundance, RCAN1-mediated suppression of these adaptive avenues of energy expenditure may now contribute to the growing epidemic of obesity.

Original languageEnglish
Article numbere44706
Number of pages19
JournalEMBO REPORTS
Volume19
Issue number12
DOIs
Publication statusE-pub ahead of print - 2018

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    Rotter, D., Peiris, H., Grinsfelder, D., Martin, A., Burchfield, J., Parra, V., Hull, C., Morales, C., Jessup, C., Matusica, D., Parks, B., Lusis, A., Nguyen, N., Oh, M., Iyoke, I., Jakkampudi, T., McMillan, D., Sadek, H., Watt, M., ... Rothermel, B. (2018). Regulator of Calcineurin 1 helps coordinate whole-body metabolism and thermogenesis. EMBO REPORTS, 19(12), [e44706]. https://doi.org/10.15252/embr.201744706