JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
·
IF 3.571
Weiwei Wang,Yiou Pan,Li Wang,Hang Zhou,Ge Song,Yongwei Wang,Jianxue Liu,Aike Li
Ferulic acid (FA) is a major polyphenolic compound and has been shown to improve the glucose and lipid homeostasis in high-fat diet-induced obese mice. Here, we found the optimal level of dietary FA to ameliorate obesity and obesity-correlated disorders, and identified the responses of gut microbiota to dietary FA in genetic leptin-deficient obese (ob/ob) mice. The ob/ob mice exhibited persistent higher body weights, feed efficiency, white adipose tissue weights, and hepatic lipid accumulation, compared to those of the wild-type mice. However, 0.5% dietary FA suppressed these symptoms in ob/ob mice. The diversity of gut microbiota and the total abundance of obesity- and anti-obesity-related genera were not influenced after FA intervention in ob/ob mice. These data suggest that sufficient intake of FA (0.5%) could be useful for treating obesity or obesity-related diseases, and this weight-control effect is possibly not correlated with the gut–brain axis.
研究领域:
营养学
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微生物学
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代谢学
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药理学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 9
·期 1
·397-406
·
IF 3.247
Zhou Yang,Fan Wu,Yanming He,Qiang Zhang,Yuan Zhang,Guangrong Zhou,Hongjie Yang,Ping Zhou
Insulin resistance caused by the overexpression of protein tyrosine phosphatase 1 B (PTP1B) as well as the dephosphorylation of its target is one of the main causes of type 2 diabetes (T2D). A newly discovered proteoglycan, Fudan-Yueyang Ganoderma lucidum (FYGL) extracted from Ganoderma lucidum, was first reported to be capable of competitively inhibiting PTP1B activity in vitro in our previous work. In the present study, we sought to reveal the mechanism of PTP1B inhibition by FYGL at the animal and cellular levels. We found that FYGL can decrease blood glucose, reduce body weight and ameliorate insulin resistance in ob/ob mice. Decrease of PTP1B expression and increase of the phosphorylation of PTP1B targets in the insulin signaling pathway of skeletal muscles were observed. In order to clearly reveal the underlying mechanism of the hypoglycemic effect caused by FYGL, we further investigated the effects of FYGL on the PTP1B-involved insulin signaling pathway in rat myoblast L6 cells. We demonstrated that FYGL had excellent cell permeability by using a confocal laser scanning microscope and a flow cytometer. We found that FYGL had a positive effect on insulin-stimulated glucose uptake by using the 2-deoxyglucose (2-DG) method. FYGL could inhibit PTP1B expression at the mRNA level, phosphorylating insulin receptor substrate-1 (IRS1), as well as activating phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt). Finally, FYGL increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and consequently up-regulated the expression of glucose transporter type 4 (GLUT4), promoting GLUT4 transportation to the plasma membrane in PTP1B-transfected L6 cells. Our study provides theoretical evidence for FYGL to be potentially used in T2D management.
研究领域:
药理学
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内分泌学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-17
·
IF 12.6
Li Li,Wang Wang,Li Rong,Guo Jiayue,Hu Xulin,Pan Yu,Zhang Taoyuan,Chi Sensen,Gu Zili,Zhu Gaohui,Liu Qi,Tan Shuai
Gut microbiota is increasingly recognized for its profound influence on host metabolism. However, the mechanisms underlying the distinct metabolic phenotype observed in germ-free (GF) mice are not fully understood. Here, the serum levels of metabolic hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were shown with significant elevation in GF than the conventionally-raised (CONV-R) mice. Single-cell transcriptome analysis revealed that Secretogranin II ( Scg2 ), with a known function in secretion control, was exclusively expressed in enteroendocrine cells (EECs). Scg2 transcript levels were significantly up-regulated in GF mice, positively correlated with enhanced GLP-1 and peptide PYY secretion. To examine the functional significance of Scg2 in hormone regulation, cross-linked nanoparticles capable of long-term adhesion to intestinal epithelium were designed, with AAV adsorbed within the cross-linked structure. This innovative design enhances its stability and retention in vivo, providing a robust platform for continuous and efficient gene delivery. We evidenced that over-expression of Scg2 via AAV-loaded nanocarriers in the colons of mice on high-fat diet or with the ob/ob genotype not only enhanced the secretion of GLP-1 and PYY but also mitigated weight gain in these mice by reducing their appetite. A multi-omics analysis reveals that Scg2 overexpression in the colon decreased hypothalamic inflammation and activated tryptophan metabolic pathways. Collectively, our findings suggest a potential therapeutic approach for treating metabolic disorders by enhancing Scg2 expression in colonic EECs. Graphical
研究领域:
分子生物学
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遗传学
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生物化学
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药理学
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纳米技术
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微生物学
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内分泌学
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代谢组学
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神经科学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Aijun Qian,Gengmiao Xiao,Zhuang Li,Yunping Mu,Xiaohong Liu,Xue Tian,Jianqin Yang,Allan Z. Zhao,Fanghong Li
The escalating obesity epidemic poses serious public health challenges, requiring the development of effective therapeutic strategies. In this study, we aimed to determine if recombinant glycoprotein hormone β5 (GPHB5) protein, particularly in the hybrid form with glycoprotein hormone α2 (GPHA2) (recombinant corticotroph-derived glycoprotein hormone, rCGH), can alleviate obesity in the genetically obese mice, ob/ob . Six-week-old male ob/ob mice were intraperitoneally injected for four weeks with rCGH (10 mg/kg) treatment. Body weight, fat mass and lean mass as well as energy expenditure were evaluated. Blood samples were collected to assess circulating concentrations of triiodothyronine (T3) and thyroxine (T4). Glucose and insulin tolerance tests were also conducted. rCGH significantly decreased body weight and fat mass, stimulated energy expenditure without alterations in food consumption, induced lipolysis and browning of white adipose tissue (WAT) by activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway. The treatment with the recombinant protein also led to marked reduction in hepatic steatosis, improved glucose tolerance and insulin sensitivity, and reduced triglycerides (TG), and total cholesterol (T-CHO) levels in ob/ob mice. In conclusion, rCGH attenuated obesity and alleviated metabolic syndromes in ob/ob mice, and it may represent a promising polypeptide-based drug candidate in treating obesity and obesity-related complications without interfering energy intake.
研究领域:
内分泌学
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代谢研究
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肥胖研究
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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