Adaptive thermogenesis enhances the life-threatening response to heat in mice with an Ryr1 mutation
Wang HJ., Lee CS., Yee RSZ., Groom L., Friedman I., Babcock L.
Retrospective Study, published in Nat Commun (2020) — summary generated from the PubMed abstract.
Early human evidence such as case series or small samples is exploring possible benefits.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Retrospective Study
- Journal
- Nat Commun (2020)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 33037202
- PMCID
- PMC7547078
- DOI
- 10.1038/s41467-020-18865-z
- Citations
- 22
Abstract (original English)
Mutations in the skeletal muscle Ca 2+ release channel, the type 1 ryanodine receptor (RYR1), cause malignant hyperthermia susceptibility (MHS) and a life-threatening sensitivity to heat, which is most severe in children. Mice with an MHS-associated mutation in Ryr1 (Y524S, YS) display lethal muscle contractures in response to heat. Here we show that the heat response in the YS mice is exacerbated by brown fat adaptive thermogenesis. In addition, the YS mice have more brown adipose tissue thermogenic capacity than their littermate controls. Blood lactate levels are elevated in both heat-sensitive MHS patients with RYR1 mutations and YS mice due to Ca 2+ driven increases in muscle metabolism. Lactate increases brown adipogenesis in both mouse and human brown preadipocytes. This study suggests that simple lifestyle modifications such as avoiding extreme temperatures and maintaining thermoneutrality could decrease the risk of life-threatening responses to heat and exercise in individuals with RYR1 pathogenic variants.
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • Without an adequate control group, treatment effects cannot be separated from other factors.
Evidence level
Early human evidence such as case series or small samples is exploring possible benefits.
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