α-Lactalbumin peptide Asp-Gln-Trp alleviates hepatic insulin resistance and modulates gut microbiota dysbiosis in high-fat diet-induced NAFLD mice

Chen, Haoran; Sun, Yun; Zhao, Haiding; Qi, Xiaofen; Cui, Hui; Ma, Ying

doi:10.1039/d2fo01343f

Cited by 25 publications

(37 citation statements)

References 67 publications

(90 reference statements)

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“…Muribaculaceae is the producer of SCFAs such as succinic acid, acetic acid, and propionic acid, which have important anti-inflammatory properties as well as effects on glucose and lipid homeostasis (53). Moreover, several studies have confirmed a positive correlation between the increased abundance of Muribaculaceae and improvement in NAFLD (54,55). Similar results were obtained in this study that Muribaculaceae had wide and negative correlations with therapeutic indicators.…”

Section: Discussionsupporting

confidence: 91%

Qingrequzhuo capsule alleviated methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice through regulating gut microbiota, enhancing gut tight junction and inhibiting the activation of TLR4/NF-κB signaling pathway

Zhang

et al. 2023

Front. Endocrinol.

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Qingrequzhuo capsule (QRQZ), composed of Morus alba L., Coptis chinensis Franch., Anemarrhena asphodeloides Bunge, Alisma plantago-aquatica subsp. orientale (Sam.) Sam., Citrus × aurantium L., Carthamus tinctorius L., Rheum palmatum L., Smilax glabra Roxb., Dioscorea oppositifolia L., Cyathula officinalis K.C.Kuan, has been used to treat nonalcoholic steatohepatitis (NASH) in clinic. However, the mechanism of QRQZ on NASH remains unclear. Recent studies have found that the dysfunction of gut microbiota could impair the gut barrier and induce the activation of TLR4/NF-kB signaling pathway, and further contribute to the inflammatory response in NASH. Modulating the gut microbiota to reduce inflammation could prevent the progression of NASH. In this study, a mouse model of NASH was generated by methionine and choline deficient diet (MCD) and treated with QRQZ. First, we evaluated the therapeutic effects of QRQZ on liver injury and inflammation in the NASH mice. Second, the changes in the gut microbiota diversity and abundance in each group of mice were measured through 16S rRNA sequencing. Finally, the effects of QRQZ on gut mucosal permeability, endotoxemia, and liver TLR4/NF-kB signaling pathway levels were examined. Our results showed that QRQZ significantly reduced the lipid accumulation in liver and the liver injury in NASH mice. In addition, QRQZ treatment decreased the levels of inflammatory cytokines in liver. 16S rRNA sequencing showed that QRQZ affected the diversity of gut microbiota and a f f e c t e d t h e r e l a t i v e a b u n d a n c e s o f D u b o s i e l l a , Lachnospiraceae_NK4A136_group, and Blautiain NASH mice. Besides, QRQZ could increase the expression of tight junction proteins (zonula occludens-1 and occludin) in gut and decrease the lipopolysaccharide (LPS) level in serum. Western blot results also showed that QRQZ treatment decreased the protein expression ofTLR4, MyD88 and the phosphorylation of IkB and NF-kBp65 and qPCR results showed that QRQZ treatment down-regulated the gene expression of interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a in liver. In conclusion, our study demonstrated that QRQZ could reduce the lipid accumulation and inflammatory response in NASH model mice. The mechanisms of QRQZ on NASH were associated with modulating gut microbiota, thereby inducing the tight junction of gut barrier, reducing the endotoxemia and inhibiting the activation of TLR4/NFkB signaling pathway in liver.

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Section: Discussionsupporting

confidence: 91%

Qingrequzhuo capsule alleviated methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice through regulating gut microbiota, enhancing gut tight junction and inhibiting the activation of TLR4/NF-κB signaling pathway

Zhang

et al. 2023

Front. Endocrinol.

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“…6(b), the community structures of HF02‐H and the ND groups were different from that of the HFD group, indicating that LP‐HF02 changed intestinal microbiota structure of obese mice. Thus, our results demonstrated that LP‐HF02 treatment improved the community richness and community structure of intestinal microbiota in obese mice, thereby increasing the microbiota resilience 36,37 …”

Section: Resultsmentioning

confidence: 54%

“…When intestinal permeability is increased, LPS can penetrate the intestinal barrier and enter into the blood, causing endotoxemia and subsequently contributing to the production of inflammatory cytokines (including IL‐1β and TNF‐α) 36 . Systemic inflammation will speed up the catabolism of TG in adipose tissue, resulting in excess FFAs influx into the liver, leading to hepatic lipids ectopic accumulation, thereby exacerbating the development of obesity 25,37 . Our data showed that the levels of serum LPS, IL‐1β and TNF‐α in obese mice were elevated by 2.10‐fold, 2.23‐fold, and 2.16‐fold, respectively, compared with the ND group, whereas LP‐HF02 remarkedly reversed these trends (Fig.…”

Section: Resultsmentioning

confidence: 80%

“…Additionally, SCFAs could reduce the pH in the intestinal lumen and subsequently inhibit the growth of LPS-producing gram-negative bacteria, thereby alleviating inflammation and dyslipidemia. 37 We speculated that LP-HF02 treatment may reduce LPS production and release through increasing the intestinal SCFA levels and subsequently inhibiting the growth of LPS-producing bacteria (e.g. Bacteroides) (Figs 7 and 8).…”

Section: Effect Of Lp-hf02 On Intestinal Barrier Integrity Inflammati...mentioning

confidence: 99%

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Lactobacillus plantarumHF02 alleviates lipid accumulation and intestinal microbiota dysbiosis in high‐fat diet‐induced obese mice

Chen

Zhao

et al. 2023

J Sci Food Agric

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BACKGROUND Obesity is closely associated with lipid accumulation and intestinal microbiota dysbiosis. It has been proved that probiotics supplement contributes to alleviate obesity. The objective of this study was to investigate the mechanism by which Lactobacillus plantarum HF02 (LP‐HF02) alleviated lipid accumulation and intestinal microbiota dysbiosis in high‐fat diet‐induced obese mice. RESULTS Our results showed that LP‐HF02 ameliorated body weight, dyslipidemia, liver lipid accumulation, and liver injury in obese mice. As expected, LP‐HF02 inhibited pancreatic lipase activity in small intestinal contents and increased fecal triglyceride levels, thereby reducing dietary fat hydrolysis and absorption. Moreover, LP‐HF02 ameliorated the intestinal microbiota composition, as evidenced by the enhanced ratio of Bacteroides to Firmicutes, the decreased abundance of pathogenic bacteria (including Bacteroides, Alistipes, Blautia, and Colidextribacter) and the increased abundance of beneficial bacteria (including Muribaculaceae, Akkermansia, Faecalibaculum, and Rikenellaceae_RC9_gut_group). LP‐HF02 also increased fecal short‐chain fatty acids (SCFAs) levels and colonic mucosal thickness, and subsequently decreased serum lipopolysaccharide (LPS), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) levels in obese mice. Additionally, reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blot results demonstrated that LP‐HF02 ameliorated hepatic lipid accumulation via activating the adenosine monophosphate (AMP)‐activated protein kinase (AMPK) pathway. CONCLUSION Therefore, our results indicated that LP‐HF02 could be considered as a probiotic preparation for preventing obesity. © 2023 Society of Chemical Industry.

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“…Our results consistently revealed that Alloprevotella was enriched by MCE supplementation, and a significant decrease in abundance of Bilophila, unclassified_f_Lachnospiraceae , unclassified_f_Oscillospiraceae , and norank_f_Oscillospiraceae was observed in the MCE group compared to the HFD group ( Figure S1 ). Moreover, the abundance of norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group has been believed to be negatively associated with the development of obesity [ 35 , 36 ]. However, in the present study, we observed that the supplementation of MCE induced a decreased abundance of norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group .…”

Section: Discussionmentioning

confidence: 99%

Dietary Supplementation of Methyl Cedryl Ether Ameliorates Adiposity in High-Fat Diet-Fed Mice

Kang

Huang

et al. 2023

Nutrients

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Methyl cedryl ether (MCE) is a derivative of cedrol and is widely used as a fragrance compound. The aim of this study was to evaluate the preventative effects of MCE on obesity and related metabolic syndromes and to delineate the mechanisms from the perspective of gut microbiota and white adipose tissues (WAT) transcriptomic profiles. Five-week-old male C57BL/6J mice were randomly assigned into 3 groups and fed with chow diet, high-fat diet (HFD), or HFD supplemented with 0.2% (w/w) MCE for 13 weeks. We found that MCE significantly reduced body weight, inhibited adipocyte hypertrophy, and ameliorated hepatic steatosis under HFD conditions. MCE dietary supplementation downregulated the expression of adipogenesis genes (FAS and C/EBPα) and upregulated the mRNA levels of thermogenesis genes (PGC-1α, PRDM16, UCP1, Cidea, Cytc, and COX4) in epididymal WAT. 16S rRNA sequencing revealed that MCE improved gut microbiota dysbiosis in HFD-fed mice, as manifested by the alteration of strains associated with obesity. Further transcriptome analysis of WAT indicated that MCE dramatically changed the gene expression profiles. Our results demonstrate the anti-obesity effect of MCE under HFD conditions, highlighting the nutraceutical potential of MCE for preventing obesity.

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α-Lactalbumin peptide Asp-Gln-Trp alleviates hepatic insulin resistance and modulates gut microbiota dysbiosis in high-fat diet-induced NAFLD mice

Abstract: The progression of nonalcoholic fatty liver disease (NAFLD) is closely related to insulin resistance and gut microbiota. Dietary interventions have emerged as effective palliative strategies for NAFLD. The present study...

Cited by 25 publications

References 67 publications

Qingrequzhuo capsule alleviated methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice through regulating gut microbiota, enhancing gut tight junction and inhibiting the activation of TLR4/NF-κB signaling pathway

Qingrequzhuo capsule alleviated methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice through regulating gut microbiota, enhancing gut tight junction and inhibiting the activation of TLR4/NF-κB signaling pathway

Lactobacillus plantarumHF02 alleviates lipid accumulation and intestinal microbiota dysbiosis in high‐fat diet‐induced obese mice

Dietary Supplementation of Methyl Cedryl Ether Ameliorates Adiposity in High-Fat Diet-Fed Mice

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