Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis.
Cell Metab
; 27(1): 195-209.e6, 2018 01 09.
Article
en En
| MEDLINE
| ID: mdl-29153407
ABSTRACT
Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic ß-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPß transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Tejido Adiposo Pardo
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Proteínas Nucleares
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Frío
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Termogénesis
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Proteínas Proto-Oncogénicas c-akt
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice
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Lipogénesis
Límite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos