Positive effect of curcumin on inflammation and mitochondrial dysfunction in obese mice with liver steatosis

Kuo,Jong-Jen; Chang,Hen-Hong; Tsai,Tung-Hu; Lee,Tzung-Yan

doi:10.3892/ijmm.2012.1049

Positive effect of curcumin on inflammation and mitochondrial dysfunction in obese mice with liver steatosis

Authors:
- Jong-Jen Kuo
- Hen-Hong Chang
- Tung-Hu Tsai
- Tzung-Yan Lee
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Affiliations: Institute of Traditional Medicine, National Yang Ming University, Taipei, Taiwan, R.O.C., Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.
Published online on: June 29, 2012 https://doi.org/10.3892/ijmm.2012.1049
Pages: 673-679

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Abstract

Obesity contributes to the increased risk of liver- related morbidity and mortality. The accumulation of macrophages in adipose tissue in an inflammatory state is a hallmark of obesity-induced hepatic steatosis. In this study, we reveal the role of curcumin in the molecular mechanisms underlying inflammatory events in a model consisting of obese mice with hepatic steatosis. Obese mice fed with curcumin experienced significant weight loss and significantly reduced serum triglyceride (TG) levels. The adipose tumor necrocis factor-α, interleukin-6 (IL-6) and monocyte chemotactic protein-1 levels were significantly higher in obese mice compared to mice fed with curcumin. Compared to the obese mice, curcumin decreased the number of F4/80-positive macrophages in epididymal adipose and liver tissue. The induction of signal transducer and activator of transcription 3 phosphorylation by curcumin resulted in the downregulation of the suppressor of cytokine signaling 3 in the liver of obese mice. Curcumin decreased hepatic TG in obese mice by downregulating the gene expression of sterol regulatory element-binding protein-1c in the liver. The hepatic expression of several mitochondrial biogenesis genes decreased in the obese mice, including mitochondrial DNA (mtDNA), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam), which are responsible for the lower mitochondrial respiratory chain (MRC) complex I activity and adenosine triphosphate production. By contrast, obese mice treated with curcumin showed normalized mtDNA, NRF1 and Tfam gene expression, reduced hepatic nuclear factor-κB activities and levels of thiobarbituric acid reactive substances (TBARS) and restored mitochondrial oxidative metabolism and biogenesis. The results from the present sudy show that curcumin prevents fatty liver disease through multiple mechanisms, and suggest that curcumin may be used to prevent the development and progression of non-alcoholic fatty liver disease (NAFLD).

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