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Regulator of Calcineurin 1 helps coordinate whole‐body metabolism and thermogenesis
Author(s) -
Rotter David,
Peiris Heshan,
Grinsfelder D Bennett,
Martin Alyce M,
Burchfield Jana,
Parra Valentina,
Hull Christi,
Morales Cyndi R,
Jessup Claire F,
Matusica Dusan,
Parks Brian W,
Lusis Aldons J,
Nguyen Ngoc Uyen Nhi,
Oh Misook,
Iyoke Israel,
Jakkampudi Tanvi,
McMillan D Randy,
Sadek Hesham A,
Watt Matthew J,
Gupta Rana K,
Pritchard Melanie A,
Keating Damien J,
Rothermel Beverly A
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744706
Subject(s) - thermogenesis , regulator , context (archaeology) , biology , endocrinology , calcineurin , adipose tissue , medicine , brown adipose tissue , microbiology and biotechnology , biochemistry , gene , transplantation , paleontology
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 ( RCAN 1 ), 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 UCP 1 expression in white adipose tissue, the other mediated by sarcolipin ( SLN ) in skeletal muscle. UCP 1 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 RCAN 1 might have been beneficial; however, in the face of caloric abundance, RCAN 1‐mediated suppression of these adaptive avenues of energy expenditure may now contribute to the growing epidemic of obesity.