Frontiers in Nutrition
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2025
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IF 5.1
Yanqiu Zhou,Junfang Shu,Yueying Zhao,Xiaorong Wu,Zhijun He,Xinzhe Lyu,Yong Zhou,Ling Ma
Background: Obesity is turning into a more critical problem for public health. Vitamin D3 (VD3) may be strongly linked to obesity.Objectives: The study aims to examine the influence of VD3 on IL-27 levels and the molecular mechanism by which VD3 affects white fat beige through the IL-27/P38MAPK/PGC-1α pathway.Methods: Firstly, a small sample population study was conducted to compare the disparities in serum 25(OH)D3 and IL-27 between individuals with obesity and healthy control groups. Secondly, twenty-four Wistar rats were separated into three groups: CON, HFD, and HFD + VD3 groups. Following 7 weeks of intervention, detection of biochemical indicators in serum by enzyme-linked immunosorbent assay (ELISA), mRNA, and protein expression of vitamin D receptor (VDR), IL-27R, P38MAPK, PGC-1α, and UCP-1 in inguinal adipose tissue by RT-qPCR and western blot. Finally, 3T3-L1 cells were induced into a hypertrophic adipose model, knock down IL-27 or PGC-1α using small interfering RNA, treated with 100 nM Calcitriol for 24 h, and divided into CON, PA, PA + 1,25(OH)2D3, PA + si IL-27, PA + si IL-27 + 1,25(OH)2D3, PA + si PGC-1α, and PA + si PGC-1α + 1,25(OH)2D3 groups. Detection of TC, TG, and IL-27 levels by ELISA, mRNA, and protein expression of VDR, IL-27R, P38MAPK, PGC-1α, UCP-1, and CD137 in cell supernatant by RT-qPCR and western blot.Results: A correlation was identified between serum 25(OH)D3 and IL-27 in the population-based study. However, no statistically significant difference in serum 25(OH)D3 or IL-27 levels was observed between the observation group and the control group. After VD3 intervention, TC, TG, and the number of LDs were significantly reduced in both HFD rats and 3T3-L1 cells, and serum IL-6 and MCP-1 in HFD rats were decreased. Meanwhile, there was a significant increase in mRNA and protein expression for VDR, IL-27R, P38MAPK, and PGC-1α. The expressions of the UCP-1 protein and the CD137 mRNA dramatically increased. Knockdown of IL-27 eliminated the increasing effect of calcitriol on the expression of P38MAPK, PGC-1α, UCP-1, and CD137 in 3T3-L1 cells, and knockdown of PGC-1α eliminated the increasing effect of calcitriol on the expression of UCP-1 and CD137 in 3T3-L1 cells.Conclusion: The study shows that VD3 may promote white fat beige through the IL-27/P38MAPK/PGC-1α pathway.
研究领域:
内分泌学
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分子生物学
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肥胖研究
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代谢紊乱
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Wang Yang-Yang,Sun Yan-Ping,Yang Bing-You,Wang Qiu-Hong,Kuang Hai-Xue
Herbs with a “hot” properties are frequently used to treat cold symptoms in TCM. However, the underlying mechanisms of the herbs with “hot” properties on hypothyroidism have not been investigated. This study aimed to explore four typical “hot” and “cold” property herb on hypothyroidism. Firstly, the difference efficacy between the four typical “hot” property herbs and the four typical “cold” property herbs was assessed by physical signs, thyroid function, and the metabolic profile using multivariate statistical analysis. The influence of the four typical “hot” property herbs on hypothyroidism was validated pathologically. The impact mechanism of the four typical “hot” property herbs on hypothyroidism was investigated through a metabolomics method combined with network analysis. Na+/K+-ATP, ACC1 enzyme, UCP-1, and the PI3K-Akt pathway were used to confirm the metabolite pathways and target-associated metabolites. The results showed that the four typical “hot” property herbs could significantly improve physical signs, thyroid function, and the metabolic profile in hypothyroidism rats, the four typical “cold” property herbs did not show any benefit. Moreover, the four typical “hot” property herbs could improve lipid metabolism, energy metabolism, and thyroid hormone levels by the PI3K-Akt signaling pathway, Ca2+- AMPK signaling pathways, purine metabolism, and tryptophan metabolism. Additionally, the levels of UCP-1, Na+/K + -ATP enzyme, and ACC1 were ameliorated by the four typical “hot” property herbs in hypothyroidism rats. Therefore, a metabolomics strategy combined with network analysis was successfully performed and interpreted the mechanism of the four typical “hot” property herbs on hypothyroidism based on the theory of “cold and hot” properties of TCM well.
研究领域:
中医中药
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药理学
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代谢组学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2023
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IF 5.6
Wenkai Zhang,Li Kong,Zhen Zhong,Lezhen Lin,Jingen Li,Guodong Zheng
To investigate the molecular mechanism of short chain fatty acids (SCFAs) on promoting fatty acid β-oxidation and browning in 3T3-L1 adipocytes. SCFAs significantly reduced lipid accumulation in 3T3-L1 adipocytes. In addition, via increasing the expression of Tfam and Nrf1, SCFAs enhanced mitochondrial biogenesis. According to the results of qPCR analysis, the expression levels of fatty acid β-oxidation genes ( PPARα , CPT1α , ACOX1 ) were up-regulated by SCFAs. Moreover, SCFAs treatment increased the genes and proteins expression of brown adipocyte-specific factors such as PRDM16, PGC-1α, and UCP-1, as well as up-regulated the genes expression of beige adipocytes markers ( Tmem26 , Tbx1 , CD137, and Cited1) . Furthermore, the effects of β3-AR and AMPK antagonist were reversed by SCFAs. In conclusion, SCFAs promote fat β-oxidation and browning of adipocytes through β3-AR/AMPKα signaling pathway, thereby reducing fat accumulation in 3T3-L1 adipocytes. Therefore, SCFAs may be a helpful supplement to combat obesity.
研究领域:
分子生物学
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细胞生物学
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代谢
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营养学
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产品关联
DOI
高影响因子
Cell Metabolism
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2022
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IF 31.373
Zu-Guo Zheng,Yin-Yue Xu,Wen-Ping Liu,Yang Zhang,Chong Zhang,Han-Ling Liu,Xiao-Yu Zhang,Run-Zhou Liu,Yi-Ping Zhang,Meng-Ying Shi,Hua Yang,Ping Li
Summary sn-1,2-diacylglycerol (sn-1,2-DAG)-mediated activation of protein kinase Cε (PKCε) is a key pathway that is responsible for obesity-related lipid metabolism disorders, which induces hepatic insulin resistance and type 2 diabetes. No small molecules have been previously reported to ameliorate these diseases through this pathway. Here, we screened and identified the phytochemical atractylenolide II (AT II) that reduces the hepatic sn-1,2-DAG levels, deactivates PKCε activity, and improves obesity-induced hyperlipidemia, hepatosteatosis, and insulin resistance. Furthermore, using the ABPP strategy, the diacylglycerol kinase family member DGKQ was identified as a direct target of AT II. AT II may act on a novel drug-binding pocket in the CRD and PH domains of DGKQ to thereby allosterically regulate its kinase activity. Moreover, AT II also increases weight loss by activating DGKQ-AMPK-PGC1α-UCP-1 signaling in adipose tissue. These findings suggest that AT II is a promising lead compound to improve obesity-induced insulin resistance.
研究领域:
药理学
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代谢
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Yangyang Wang,Yanping Sun,Bingyou Yang,Qiuhong Wang,Haixue Kuang
Ethnopharmacological relevance The ‘cold’ property herbs are commonly applied in heat syndrome. Unfortunately, the underlying mechanisms of the ‘cold’ property herbs on heat syndrome has not been investigated. Aim of the study The study aimed to probe the activities of the four typical ‘cold’ property herbs on hyperthyroidism . Materials and methods Firstly, the four typical ‘heat’ property herbs were set as contrasting experiment. Then. the physical sign, thyroid function and metabolism profile (multivariate statistical analysis) were assessing the difference between the four typical ‘cod’ property herbs and the four typical ‘heat’ property herbs. H&E staining were used to confirmed the influence of the typical ‘cold’ property herbs on hyperthyroidism. A metabolomics approach combine with network pharmacology were explored the effected mechanism of the typical ‘cold’ property herbs on hyperthyroidism. the gene expression of UCP-1 was detected by RT-PCR. The metabolites pathway and target-associated metabolites were verified Na + /K + -ATP enzyme and GSH, as well IL6, IL17, MAPK and PPAR-γ, which detected by commercial kits and Western blot . Results It is proved that the four typical ‘cold’ property herbs effectively ameliorate the physical sign, thyroid function and metabolism profile in hyperthyroidism rats, but the four typical ‘heat’ property herbs showed no benefit. Moreover, the four typical ‘cold’ property herbs regulated energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, thyroid hormone synthesis, arachidonic acid metabolism and linoleic acid metabolism and the inflammation mediated by inflammatory factor (IL6, IL17), Ca 2+ and MAPK signaling pathway. And the levels of UCP-1, Na + /K + -ATP enzyme, GSH, and the targets protein of IL6, IL17, MAPK and PPAR-γ were ameliorated by the four typical ‘cold’ property herbs. Conclusion The four typical ‘cold’ property herbs could alleviate hyperthyroidism by ameliorate thyroid hormone synthesis, restraining inflammation and oxidative stress via regulating energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, arachidonic acid metabolism and linoleic acid metabolism and Ca 2+ /MAPK signaling pathway, which might be a useful strategy for treating hyperthyroidism.
研究领域:
民族药理学
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代谢组学
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药理学
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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