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. 2022 Aug 3:9:959906.
doi: 10.3389/fvets.2022.959906. eCollection 2022.

Dietary Grape Seed Proanthocyanidin Alleviates the Liver Injury Induced by Long-Term High-Fat Diets in Sprague Dawley Rats

Hao Yang Sun  1 , Ai Xin Gu  1 , Bi Ying Huang  1 , Tong Zhang  1 , Jian Ping Li  1 , An Shan Shan  1
Affiliations

Dietary Grape Seed Proanthocyanidin Alleviates the Liver Injury Induced by Long-Term High-Fat Diets in Sprague Dawley Rats

Hao Yang Sun et al. Front Vet Sci. .

Abstract

In mammals, the liver is the most important organ that plays a vital function in lipid metabolism. Grape seed proanthocyanidin (GSPE) is a kind of natural polyphenolic compound primarily obtained from grape skin and seeds. Recent research found it had high bioavailability in defending against obesity, hyperlipidemia, inflammatory, oxidative stress, and targeting liver tissue. However, the mechanism of GSPE in regulating obesity induced by dietary high-fat (HF) was not fully understood, particularly the influences on liver functions. Therefore, this study aimed to investigate the effects of GSPE supplementation on the liver function and lipid metabolic parameters in rats fed HF diets long-term. A total of 40 healthy female Sprague Dawley rats were selected. After 8 weeks of obesity model feeding, the rats were randomly divided into four treatments: NC, standard diet; NC + GSPE, standard diet + 500 mg/kg body weight GSPE; HF, high-fat diet; HG + GSPE, high fat diet + 500 mg/kg body weight GSPE. Results indicated that long-term HF feeding caused severe liver problems including megalohepatia, steatosis, inflammation, and hepatocyte apoptosis. The supplementation of GSPE alleviated these symptoms. The results of the current experiment confirmed that GSPE addition up-regulated the expression of the Wnt3a/β-catenin signaling pathway, thereby restraining the liver cell endoplasmic reticulum stress and hepatocyte apoptosis. Furthermore, the microRNA-103 may play a role in this signal-regulated pathway. In summary, GSPE had a protective effect on the liver and the current experiment provided a reference for the application of GSPE in animal nutrition as a kind of natural feed additive.

Keywords: Wnt3a/β-catenin signaling pathway; endoplasmic reticulum stress; grape seed proanthocyanidin; lipid metabolism; liver injury; microRNA.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Effects of GSPE on liver index in rats fed long-term high-fat diet. Data were expressed as the mean ± SEM. Different letters means with different superscripts differ (P < 0.05). NC, standard diet; NC + G, standard diet + 500 mg/kg body weight GSPE; HF, high fat diet; HF + G, high fat diet + 500 mg/kg body weight GSPE.
Figure 2
Figure 2
(A) NC, standard diet; (B) NC + G, standard diet + 500 mg/kg body weight GSPE; (C) HF, high fat diet; (D) HF + G, high fat diet + 500 mg/kg body weight GSPE.
Figure 3
Figure 3
Effects of GSPE on relative expression of lipid metabolism genes of liver in rats fed long-term high-fat diet [(A) PPARγ mRNA expression; (B) FAS mRNA expression]. Data were expressed as the mean ± SEM. Different letters means with different superscripts differ (P < 0.05). NC, standard diet; NC + G, standard diet + 500 mg/kg body weight GSPE; HF, high fat diet; HF + G, high fat diet + 500 mg/kg body weight GSPE.
Figure 4
Figure 4
Effects of GSPE on relative expression of endoplasmic reticulum stress of liver in rats fed long-term high-fat diet [(A) ATF6 mRNA expression; (B) CHOP mRNA expression; (C) Protein production on ATF6 gene; (D) Protein production on CHOP gene]. Data were expressed as the mean ± SEM. Different letters means with different superscripts differ (P < 0.05). NC, standard diet; NC + G, standard diet + 500 mg/kg body weight GSPE; HF, high fat diet; HF + G, high fat diet + 500 mg/kg body weight GSPE.
Figure 5
Figure 5
Effects of GSPE on relative expression of apoptosis proteins of liver in rats fed long-term high-fat diet [(A) Bax mRNA expression; (B) Bcl-2 mRNA expression; (C) Caspase-3 mRNA expression]. Data were expressed as the mean ± SEM. Different letters means with different superscripts differ (P < 0.05). NC, standard diet; NC + G, standard diet + 500 mg/kg body weight GSPE; HF, high fat diet; HF + G, high fat diet + 500 mg/kg body weight GSPE.
Figure 6
Figure 6
Effects of GSPE on relative expression of inflammatory cytokines of liver in rats fed long-term high-fat diet [(A) TNF-α mRNA expression; (B) IL-1β mRNA expression; (C) IL-6 mRNA expression]. Data were expressed as the mean ± SEM. Different letters means with different superscripts differ (P < 0.05). NC, standard diet; NC + G, standard diet + 500 mg/kg body weight GSPE; HF, high fat diet; HF + G, high fat diet + 500 mg/kg body weight GSPE.
Figure 7
Figure 7
Effects of GSPE on relative expression of micro-RNA-103 of liver in rats fed long-term high-fat diet. Data were expressed as the mean ± SEM. Different letters means with different superscripts differ (P < 0.05). NC, standard diet; NC + G, standard diet + 500 mg/kg body weight GSPE; HF, high fat diet; HF + G, high fat diet + 500 mg/kg body weight GSPE.
Figure 8
Figure 8
Effects of GSPE on Wnt3a/β-catenin pathway protein concentration and expression of liver in rats fed long-term high-fat diet [(A) Wnt3a protein concentration; (B) β-catenin protein concentration; (C) Protein production on Wnt3a; (D) Protein production on β-catenin]. Data were expressed as the mean ± SEM. Different letters means with different superscripts differ (P < 0.05). NC, standard diet; NC + G, standard diet + 500 mg/kg body weight GSPE; HF, high fat diet; HF + G, high fat diet + 500 mg/kg body weight GSPE.
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