Dataset Information

Combined intake of blueberry juice and probiotics ameliorate mitochondrial dysfunction by activating SIRT1 in alcoholic fatty liver disease.

ABSTRACT:

Background

Mitochondrial dysfunction has been implicated as a significant factor in the liver disease process. Blueberry juice and probiotics (BP) synergistically improve liver function in alcoholic fatty liver disease (AFLD), although the mechanism for this effect was unclear. This study aims to investigate the effect and specific mechanisms of BP on AFLD.

Methods

C57/BL6 mice were randomly divided into seven groups: CG (control), MG (AFLD model), BJ (MG mice treated with blueberry), BJB (MG mice treated with BP), SI (AFLD mice treated with SIRT1 siRNA), BJSI (SI mice treated with blueberry), and BJBSI (SI mice treated with BP). The mice were fed an alcohol liquid diet for 10 days to establish the AFLD model, and subjected to BP and SIRT1 siRNA intervention for 10 days. Liver pathology was performed on day 11, and biochemical and molecular analyses of liver mitochondria were employed on day 12.

Results

BP significantly ameliorated hepatic mitochondrial injury, mitochondrial swelling, and hepatic necrosis in AFLD. BP alleviated hepatic mitochondrial dysfunction by increasing the expression of succinate dehydrogenase and cytochrome c oxidase, increasing respiratory control rate and the ADP/O ratio, and facilitating the synthesis of energy-related molecules. Besides, BP increased the expression of glutathione and superoxide dismutase, and inhibited malondialdehyde expression and reactive oxygen species activity. BP-induced sirtuin 1 (SIRT1), which activates peroxisome proliferator-activated receptor-gamma coactivator-1α, both of which mediate mitochondrial homeostasis. SIRT1 silencing suppressed the BP-induced changes in liver mitochondria, blunting its efficacy.

Conclusions

The ingredients of BP ameliorate hepatocyte mitochondrial dysfunction in AFLD mice.

SUBMITTER: Fan H

PROVIDER: S-EPMC8108333 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7?-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-? protein was significantly increased while the expression of PPAR-? and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-? protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-? and SREBP-1c, and through normalizing the intestinal dysbiosis and improving the intestinal mucosal barrier function.