{"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}
引用次数: 0
Abstract
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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