KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
·
2024
·
IF 1.6
Yan Sun,Hai Qu,Xiaohong Niu,Ting Li,Lijuan Wang,Hairui Peng
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro , high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.
研究领域:
药理学
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内分泌学
·
糖尿病研究
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代谢
·
胃肠生理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
EBioMedicine
·
2024
·
IF 9.7
Harry Cheuk-Hay Lau,Xiang Zhang,Fenfen Ji,Yufeng Lin,Wei Liang,Qing Li,Danyu Chen,Winnie Fong,Xing Kang,Weixin Liu,Eagle Siu-Hong Chu,Queena Wing-Yin Ng,Jun Yu
Abstract
Background: Gut probiotic depletion is associated with non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). Here, we investigated the prophylactic potential of Lactobacillus acidophilus against NAFLD-HCC.
Methods: NAFLD-HCC conventional and germ-free mice were established by diethylnitrosamine (DEN) injection with feeding of high-fat high-cholesterol (HFHC) or choline-deficient high-fat (CDHF) diet. Orthotopic NAFLD-HCC allografts were established by intrahepatic injection of murine HCC cells with HFHC feeding. Metabolomic profiling was performed using liquid chromatography-mass spectrometry. Biological functions of L. acidophilus conditional medium (L.a CM) and metabolites were determined in NAFLD-HCC human cells and mouse organoids.
Findings: L. acidophilus supplementation suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice. This was confirmed in orthotopic allografts and germ-free tumourigenesis mice. L.a CM inhibited the growth of NAFLD-HCC human cells and mouse organoids. The protective function of L. acidophilus was attributed to its non-protein small molecules. By metabolomic profiling, valeric acid was the top enriched metabolite in L.a CM and its upregulation was verified in liver and portal vein of L. acidophilus-treated mice. The protective function of valeric acid was demonstrated in NAFLD-HCC human cells and mouse organoids. Valeric acid significantly suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice, accompanied by improved intestinal barrier integrity. This was confirmed in another NAFLD-HCC mouse model induced by CDHF diet and DEN. Mechanistically, valeric acid bound to hepatocytic surface receptor GPR41/43 to inhibit Rho-GTPase pathway, thereby ablating NAFLD-HCC.
Interpretation: L. acidophilus exhibits anti-tumourigenic effect in mice by secreting valeric acid. Probiotic supplementation is a potential prophylactic of NAFLD-HCC.
研究领域:
微生物学
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肝病学
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癌症生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 9
·1-18
·
IF 2.6
Xu Wenyi,Guan Yinghua,Tian Liping,Fu Yu,Zhang Yinghui,Liu Yanhong,Hu Yanfei,Zhao Bowen,Wu Chongming
The global prevalence of type 2 diabetes mellitus (T2DM) is currently surging, posing significant health and socioeconomic burdens. Probiotics have emerged as promising interventions due to their safety and potential metabolic benefits. Gut microbiota plays a critical role in the pathophysiology of metabolic diseases in humans, offering valuable insights for therapeutic strategies such as probiotics. Here, aiming to identify novel probiotics from the human gut microbes to combat T2DM, a total of 203 human intestinal bacterial strains were screened in vitro to evaluate their enzymatic inhibition of α-glucosidase and α-amylase, in which Lacticaseibacillus paracasei Glu-07 (= QH-142 = CGMCC 23796) exhibited the highest inhibitory efficacy (81.05% and 72.56% for α-glucosidase and α-amylase, respectively). In HepG2 cells, L. paracasei Glu-07 elevated glucose uptake and consumption by 22.4% and 85.8%. Oral administration of strain Glu-07 in diabetic mice significantly improved hyperglycemia, hyperlipidemia, and restored the structure and composition of gut microbiota toward a healthier profile. Mechanistically, strain Glu-07 activated the AMPK-AKT1-GSK3β/FOXO1 signaling pathways by modulating the expression of key genes, enhanced glycolysis and fatty acid ꞵ-oxidation, and inhibited gluconeogenesis and lipogenesis. It also stimulated GLP-1 secretion, potentially via triggering the GPR41/43-GLP-1 axis, and increased the abundance of beneficial gut microbes, such as Akkermansia muciniphila (~ threefold). The dual regulations synergistically support strain Glu-07 as a promising probiotic candidate for T2DM management.
研究领域:
微生物学
·
糖尿病研究
·
分子生物学
·
药理学
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营养科学
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代谢性疾病
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）