Local hyperthermia therapy induces browning of white fat and treats obesity.
Cell
; 185(6): 949-966.e19, 2022 03 17.
Article
em En
| MEDLINE
| ID: mdl-35247329
ABSTRACT
Beige fat plays key roles in the regulation of systemic energy homeostasis; however, detailed mechanisms and safe strategy for its activation remain elusive. In this study, we discovered that local hyperthermia therapy (LHT) targeting beige fat promoted its activation in humans and mice. LHT achieved using a hydrogel-based photothermal therapy activated beige fat, preventing and treating obesity in mice without adverse effects. HSF1 is required for the effects since HSF1 deficiency blunted the metabolic benefits of LHT. HSF1 regulates Hnrnpa2b1 (A2b1) transcription, leading to increased mRNA stability of key metabolic genes. Importantly, analysis of human association studies followed by functional analysis revealed that the HSF1 gain-of-function variant p.P365T is associated with improved metabolic performance in humans and increased A2b1 transcription in mice and cells. Overall, we demonstrate that LHT offers a promising strategy against obesity by inducing beige fat activation via HSF1-A2B1 transcriptional axis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo Branco
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Tecido Adiposo Bege
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Hipertermia Induzida
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Obesidade
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article