Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats

Chang, Xinxia; Yan, Hongmei; Jing, Fei; Jiang, Minghong; Zhu, Hongguang; Lu, Daru; Gao, Xin

doi:10.1194/jlr.m001958

Cited by 141 publications

(114 citation statements)

References 38 publications

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“…1S). Similar to our results, liver Dnmt1 mRNA [11] and/or protein [53] was not affected by the HFD. In human skeletal muscle, mRNA levels of both DNMT3a and DNMT3b were not significantly changed by a short period of high-fat overfeeding [4].…”

Section: Discussionsupporting

confidence: 80%

DNA Methylation Changes Induced by a High-Fat Diet and Fish Oil Supplementation in the Skeletal Muscle of Mice

et al. 2014

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Background/Aims: To investigate the global changes in DNA methylation and methylation of the promoter region of the peroxisome proliferator-activated receptor gamma transcript variant 2 (Pparg2) gene resulting from a high-fat diet (HFD) and/or fish oil supplementation. Methods: Fish oil, rich in omega-3 polyunsaturated fatty acids, or water was orally administered to male mice for 12 weeks. After the first 4 weeks, the animals were fed a control diet or an HFD until the end of the experimental protocol, when the epididymal fat, gastrocnemius muscle and liver were excised. Results:Pparg2 mRNA expression was upregulated by obesity and downregulated by fish oil supplementation in the liver. In the gastrocnemius muscle, diet-induced obesity increased global DNA methylation. Fish oil prevented the decrease in Pparg2 promoter methylation induced by obesity in the gastrocnemius muscle. Regardless of the diet given, fish oil supplementation increased Pparg2 promoter methylation at CpG-263 in muscle and adipose tissue. Conclusion: HFD and fish oil modified global and Pparg2 promoter DNA methylation in a tissue-specific manner. Fish oil supplementation attenuated body weight gain, abolished the increase in Pparg2 expression in the liver and prevented the decrease in Pparg2 promoter methylation in the muscle induced by the HFD.

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Section: Discussionsupporting

confidence: 80%

DNA Methylation Changes Induced by a High-Fat Diet and Fish Oil Supplementation in the Skeletal Muscle of Mice

et al. 2014

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“…The nutritional regulation on the epigenome during liver development is very limited. HF diets had been shown to mediate DNA methylation at specific CpG sites on the promoter of gene and affected gene expression, thereby leading to physiological alterations (4,7,10,11,18,29). A recent study that applied Illumina's Infinium Bead Array assessed at 27,578 CpG sites associated with 14,475 genes has shown that a short-term feeding of HF diet induced genome-wide DNA methylation change at CpG sites in the skeletal muscle of healthy young men (17).…”

Section: Discussionmentioning

confidence: 99%

High-fat diet caused widespread epigenomic differences on hepatic methylome in rat

Zhang

Wang

Zhou

et al. 2015

Physiological Genomics

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Pan YX. High-fat diet caused widespread epigenomic differences on hepatic methylome in rat. Physiol Genomics 47: 514 -523, 2015. First published July 21, 2015; doi:10.1152/physiolgenomics.00110.2014.-A high-fat (HF) diet is associated with progression of liver diseases. To illustrate genome-wide landscape of DNA methylation in liver of rats fed either a control or HF diet, two enrichment-based methods, namely methyl-DNA immunoprecipitation assay with high-throughput sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq), were performed in our study. Rats fed with the HF diet exhibited an increased body weight and liver fat accumulation compared with that of the control group when they were 12 wk of age. Genome-wide analysis of differentially methylated regions (DMRs) showed that 12,494 DMRs induced by HF diet were hypomethylated and 6,404 were hypermethylated. DMRs with gene annotations [differentially methylated genes (DMGs)] were further analyzed to show gene-specific methylation profile. There were 88, 2,680, and 95 hypomethylated DMGs identified with changes in DNA methylation in the promoter, intragenic and downstream regions, respectively, compared with fewer hypermethylated DMGs (45, 1,623, and 50 in the respective regions). Some of these genes also contained an ACGT cis-acting motif whose DNA methylation status may affect gene expression. Pathway analysis showed that these DMGs were involved in critical hepatic signaling networks related to hepatic development. Therefore, HF diet had global impacts on DNA methylation profile in the liver of rats, leading to differential expression of genes in hepatic pathways that may involve in functional changes in liver development. DMR; DNA hypomethylation; gene expression; high-fat diet; MeDIP THE INTERACTION BETWEEN NUTRITIONAL and epigenetic influences on the gene regulation is of great interest to researchers (27). For decades, due to the limitation and cost of the experimental technology for detecting DNA methylation (6), most studies focused on how diet affects the promoter methylation profile of a single gene and its relationship with gene expression. Recent advancements in sequencing-based DNA methylation profiling methods including methyl-DNA immunoprecipitation assay in combination with high-throughput sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq) have allowed researchers to map out DNA methylation profile in a genome-wide fashion (30).Consumption of a high-fat (HF) diet may cause numerous health consequences, including extensive hepatic triglyceride accumulation, insulin resistance, oxidative damage, and chronic low-grade inflammation, which leads to progression of liver diseases and fibrosis (2,8,34). Metabolism and cell cycle-related genes in liver tissue are known to be subject to regulation by DNA methylation. For instance, methylation intensity at specific CpG sites on Esr1 (7) and stearoyl-CoA desaturase 1 (Scd1) (29), glucokinase, pyruvate kinase (18), and MTTP (4) genes ...

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“…Chinese herbs have been traditionally used for treating liver disease worldwide (37), and there are numerous herbal products that are believed to benefit patients with NAFLD, with acceptable levels of safety. For example, previous studies have demonstrated that puerarin, baicalin and berberine, which are three major constituents of the Chinese herbs: Puerariae Radix, Scutellariae Radix and Coptidis Rhizoma, exhibit therapeutic effects on rats with NAFLD (20)(21)(22). However, there have been few reports regarding the compatibility of these constituents.…”

mentioning

confidence: 98%

“…1A-C), are three major constituents of the Chinese herbs: Puerariae Radix [roots of Pueraria lobata (Willd.) Ohwi, PR], Scutellariae Radix (roots of Scutellaria baicalensis Georgi SR) and Coptidis Rhizoma (rhizomes of Coptis chinensis Franch, CR), which have demonstrated therapeutic effects on rats models of NAFLD (20)(21)(22). It is believed that a combination of agents may effectively reduce side effects and improve adaptive resistance.…”

Section: Introductionmentioning

confidence: 99%

Effects of a combination of puerarin, baicalin and berberine on the expression of proliferator-activated receptor-γ and insulin receptor in a rat model of nonalcoholic fatty liver disease

Zhao

Liu

Wang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Nonalcoholic fatty liver disease (NAFLD) is a prevalent disease, with a clinical spectrum ranging from simple fatty liver disease to nonalcoholic steatohepatitis and cirrhosis. Puerarin, baicalin and berberine are herbal products widely used in Asia, which are believed to possess therapeutic benefits for alleviating the symptoms of NAFLD. In the present study, a rat model of NAFLD, induced by a high-fat diet, was established and orthographical experimentation was used to investigate the effects of various combinations of puerarin, baicalin and berberine on the hepatic expression of proliferator-activated receptor (PPAR)-γ and insulin receptor (IR). The present study demonstrated that serum levels of total cholesterol, alanine transaminase and low-density lipoproteins were significantly decreased in the puerarin-dominated groups (P<0.05 vs. the model group), whereas the concentrations of tumor necrosis factor-α and interleukin-6 were significantly improved in the baicalin-and berberine-dominated groups (P<0.05 vs. the model group). Furthermore, as compared with the control group, the levels of PPAR-γ/IR mRNA and protein expression were significantly decreased in the model group (P<0.01), and significantly increased in the rosiglitazone group and some of the orthogonal experiment groups (P<0.01). In conclusion, a combination of puerarin, baicalin and berberine induced favorable effects on NAFLD by upregulating hepatic PPAR-γ and IR expression levels, and different proportions of monomer compositions exerted variable positive effects on various stages of NAFLD.

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Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats

Cited by 141 publications

References 38 publications

DNA Methylation Changes Induced by a High-Fat Diet and Fish Oil Supplementation in the Skeletal Muscle of Mice

DNA Methylation Changes Induced by a High-Fat Diet and Fish Oil Supplementation in the Skeletal Muscle of Mice

High-fat diet caused widespread epigenomic differences on hepatic methylome in rat

Effects of a combination of puerarin, baicalin and berberine on the expression of proliferator-activated receptor-γ and insulin receptor in a rat model of nonalcoholic fatty liver disease

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