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Updated: Jun 16, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Mitochondrial dysfunction caused by SIRT3 inhibition drives proinflammatory macrophage polarization in obesity
Qing Zhou1, Yuyan Wang2, Zongshi Lu1
1Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, and Chongqing Institute of Hypertension, Chongqing, China.
Objective:
Metabolic reprogramming is a main feature of proinflammatory macrophage polarization, a process that leads to inflammation in dysfunctional adipose tissue. Therefore, the study aim was to explore whether sirtuin 3 (SIRT3), a mitochondrial deacetylase, participates in this pathophysiological process.
Methods:
Macrophage-specific Sirt3 knockout (Sirt3-MKO) mice and wild-type littermates were treated with a high-fat diet. Body weight, glucose tolerance, and inflammation were evaluated. Bone marrow-derived macrophages and RAW264.7 cells were treated with palmitic acid to explore the mechanism of SIRT3 on inflammation.
Results:
The expression of SIRT3 was significantly repressed in both bone marrow-derived macrophages and adipose tissue macrophages in mice fed with a high-fat diet. Sirt3-MKO mice exhibited accelerated body weight and severe inflammation, accompanied with reduced energy expenditure and worsened glucose metabolism. In vitro experiments showed that SIRT3 inhibition or knockdown exacerbated palmitic acid-induced proinflammatory macrophage polarization, whereas SIRT3 restoration displayed opposite effects. Mechanistically, SIRT3 deficiency resulted in hyperacetylation of succinate dehydrogenase that led to succinate accumulation, which suppressed the transcription of Kruppel-like factor 4 via increasing histone methylation on its promoter, thus evoking proinflammatory macrophages.
Conclusions:
This study emphasizes an important preventive role of SIRT3 in macrophage polarization and implies that SIRT3 is a promising therapeutic target for obesity.
