期刊
EMBO REPORTS
卷 19, 期 12, 页码 -出版社
WILEY
DOI: 10.15252/embr.201744706
关键词
adaptive thermogenesis; Down syndrome; obesity; RCAN1; sarcolipin
资金
- National Institutes of Health [HL072016, HL102478, 1U54HD087351, DK104789]
- American Heart Association [11POST7950051, 13POST16520009]
- Australian National Health and Medical Research Council [APP1088737]
- National Fund for Scientific and Technological Development in Chile [FONDECYT 11150282, PAI 79150007]
- Diabetes Australia Research Trust [Y16G-KEAD]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [U54HD087351] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL102478] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK104789] Funding Source: NIH RePORTER
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.
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