Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health.
Nat Metab
; 6(7): 1329-1346, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-39009762
ABSTRACT
Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ratones Noqueados
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Adipocitos
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Metabolismo Energético
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Glutaminasa
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Nat Metab
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suecia