Itaconate alleviates diet-induced obesity via activation of brown adipocyte thermogenesis.
Cell Rep
; 43(5): 114142, 2024 May 28.
Article
in En
| MEDLINE
| ID: mdl-38691458
ABSTRACT
Despite medical advances, there remains an unmet need for better treatment of obesity. Itaconate, a product of the decarboxylation of the tricarboxylic acid cycle intermediate cis-aconitate, plays a regulatory role in both metabolism and immunity. Here, we show that itaconate, as an endogenous compound, counteracts high-fat-diet (HFD)-induced obesity through leptin-independent mechanisms in three mouse models. Specifically, itaconate reduces weight gain, reverses hyperlipidemia, and improves glucose tolerance in HFD-fed mice. Additionally, itaconate enhances energy expenditure and the thermogenic capacity of brown adipose tissue (BAT). Unbiased proteomic analysis reveals that itaconate upregulates key proteins involved in fatty acid oxidation and represses the expression of lipogenic genes. Itaconate may provoke a major metabolic reprogramming by inducing fatty acid oxidation and suppression of fatty acid synthesis in BAT. These findings highlight itaconate as a potential activator of BAT-mediated thermogenesis and a promising candidate for anti-obesity therapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Succinates
/
Thermogenesis
/
Adipocytes, Brown
/
Diet, High-Fat
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Mice, Inbred C57BL
/
Obesity
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2024
Document type:
Article
Affiliation country:
China