{"title":"维生素D3通过IL-27/P38MAPK/PGC-1α途径促进白色脂肪米色。","authors":"Yanqiu Zhou, Junfang Shu, Yueying Zhao, Xiaorong Wu, Zhijun He, Xinzhe Lyu, Yong Zhou, Ling Ma","doi":"10.3389/fnut.2025.1661072","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Obesity is turning into a more critical problem for public health. Vitamin D<sub>3</sub> (VD<sub>3</sub>) may be strongly linked to obesity.</p><p><strong>Objectives: </strong>The study aims to examine the influence of VD<sub>3</sub> on IL-27 levels and the molecular mechanism by which VD<sub>3</sub> affects white fat beige through the IL-27/P38MAPK/PGC-1α pathway.</p><p><strong>Methods: </strong>Firstly, a small sample population study was conducted to compare the disparities in serum 25(OH)D<sub>3</sub> 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 + VD<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub>, PA + si IL-27, PA + si IL-27 + 1,25(OH)<sub>2</sub>D<sub>3,</sub> PA + si PGC-1α, and PA + si PGC-1α + 1,25(OH)<sub>2</sub>D<sub>3</sub> 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.</p><p><strong>Results: </strong>A correlation was identified between serum 25(OH)D<sub>3</sub> and IL-27 in the population-based study. However, no statistically significant difference in serum 25(OH)D<sub>3</sub> or IL-27 levels was observed between the observation group and the control group. After VD<sub>3</sub> 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.</p><p><strong>Conclusion: </strong>The study shows that VD<sub>3</sub> may promote white fat beige through the IL-27/P38MAPK/PGC-1α pathway.</p>","PeriodicalId":12473,"journal":{"name":"Frontiers in Nutrition","volume":"12 ","pages":"1661072"},"PeriodicalIF":4.0000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488405/pdf/","citationCount":"0","resultStr":"{\"title\":\"Vitamin D<sub>3</sub> promotes white fat beige through IL-27/P38MAPK/PGC-1α pathway.\",\"authors\":\"Yanqiu Zhou, Junfang Shu, Yueying Zhao, Xiaorong Wu, Zhijun He, Xinzhe Lyu, Yong Zhou, Ling Ma\",\"doi\":\"10.3389/fnut.2025.1661072\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Obesity is turning into a more critical problem for public health. Vitamin D<sub>3</sub> (VD<sub>3</sub>) may be strongly linked to obesity.</p><p><strong>Objectives: </strong>The study aims to examine the influence of VD<sub>3</sub> on IL-27 levels and the molecular mechanism by which VD<sub>3</sub> affects white fat beige through the IL-27/P38MAPK/PGC-1α pathway.</p><p><strong>Methods: </strong>Firstly, a small sample population study was conducted to compare the disparities in serum 25(OH)D<sub>3</sub> 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 + VD<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub>, PA + si IL-27, PA + si IL-27 + 1,25(OH)<sub>2</sub>D<sub>3,</sub> PA + si PGC-1α, and PA + si PGC-1α + 1,25(OH)<sub>2</sub>D<sub>3</sub> 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.</p><p><strong>Results: </strong>A correlation was identified between serum 25(OH)D<sub>3</sub> and IL-27 in the population-based study. However, no statistically significant difference in serum 25(OH)D<sub>3</sub> or IL-27 levels was observed between the observation group and the control group. After VD<sub>3</sub> 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.</p><p><strong>Conclusion: </strong>The study shows that VD<sub>3</sub> may promote white fat beige through the IL-27/P38MAPK/PGC-1α pathway.</p>\",\"PeriodicalId\":12473,\"journal\":{\"name\":\"Frontiers in Nutrition\",\"volume\":\"12 \",\"pages\":\"1661072\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488405/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Nutrition\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.3389/fnut.2025.1661072\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Nutrition","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.3389/fnut.2025.1661072","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
摘要
背景：肥胖正在成为公共健康的一个更为严重的问题。维生素D3 （VD3）可能与肥胖密切相关。目的：研究VD3通过IL-27/P38MAPK/PGC-1α通路影响白色脂肪米色的分子机制及VD3对IL-27水平的影响。方法：首先采用小样本人群研究，比较肥胖个体与健康对照组血清25(OH)D3和IL-27的差异。其次，将24只Wistar大鼠分为CON、HFD和HFD + VD3组。干预7 周后，采用酶联免疫吸附法（ELISA）检测血清生化指标，RT-qPCR和western blot检测腹股沟脂肪组织中维生素D受体（VDR）、IL-27R、P38MAPK、PGC-1α、UCP-1 mRNA和蛋白表达。最后,3 t3-l1细胞诱导为肥厚性脂肪模型,击倒IL-27或PGC-1α使用小型干扰RNA, 100 海里骨化三醇治疗24 h,并分为案子,PA, PA + 1,25 (OH) 2 d3, PA + si IL-27, PA + si IL-27 + 1,25 (OH) 2 d3, PA + si PGC-1α,和PA + si PGC-1α + 1,25 (OH) 2 d3组。ELISA检测TC、TG、IL-27水平，RT-qPCR和western blot检测细胞上清中VDR、IL-27R、P38MAPK、PGC-1α、UCP-1、CD137蛋白的表达。结果：在以人群为基础的研究中，血清25(OH)D3和IL-27之间存在相关性。观察组与对照组血清25(OH)D3、IL-27水平差异无统计学意义。VD3干预后，HFD大鼠和3T3-L1细胞的TC、TG、ld数量均显著降低，血清IL-6、MCP-1降低。同时，VDR、IL-27R、P38MAPK、PGC-1α mRNA和蛋白表达均显著升高。UCP-1蛋白和CD137 mRNA的表达显著升高。敲低IL-27可消除骨化三醇对3T3-L1细胞中P38MAPK、PGC-1α、UCP-1和CD137表达的增加作用，敲低PGC-1α可消除骨化三醇对3T3-L1细胞中UCP-1和CD137表达的增加作用。结论：研究表明VD3可能通过IL-27/P38MAPK/PGC-1α通路促进白色脂肪米色。
Vitamin D3 promotes white fat beige through IL-27/P38MAPK/PGC-1α pathway.
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.
期刊介绍：
No subject pertains more to human life than nutrition. The aim of Frontiers in Nutrition is to integrate major scientific disciplines in this vast field in order to address the most relevant and pertinent questions and developments. Our ambition is to create an integrated podium based on original research, clinical trials, and contemporary reviews to build a reputable knowledge forum in the domains of human health, dietary behaviors, agronomy & 21st century food science. Through the recognized open-access Frontiers platform we welcome manuscripts to our dedicated sections relating to different areas in the field of nutrition with a focus on human health.
Specialty sections in Frontiers in Nutrition include, for example, Clinical Nutrition, Nutrition & Sustainable Diets, Nutrition and Food Science Technology, Nutrition Methodology, Sport & Exercise Nutrition, Food Chemistry, and Nutritional Immunology. Based on the publication of rigorous scientific research, we thrive to achieve a visible impact on the global nutrition agenda addressing the grand challenges of our time, including obesity, malnutrition, hunger, food waste, sustainability and consumer health.
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