ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1661072
Vitamin D3 promotes white fat beige through IL-27/P38MAPK/PGC-1α pathway
Provisionally accepted
- 1Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, 646000, China, Luzhou, China
- 2Department of Clinical Nutrition, Chongqing General Hospital, Chongqing University, Chongqing, 401147, China, Chongqing, China
- 3School of Public Health, Southwest Medical University, Luzhou, 646000, China, Luzhou, China
- 4Department of Medical Cell Biology and Genetics, School of Basic Medical Science, Southwest Medical University, Luzhou, 646000, China, Luzhou, China
- 5Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, 646000, China, Luzhou, China
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Background: Obesity is turning into a more critical problem for public health. Vitamin D3 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 seven weeks of intervention, detection of biochemical indicators in serum by ELISA, mRNA and protein expression of VDR, IL-27R, P38MAPK, PGC-1α, 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 100nM Calcitriol for 24h, 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 observation group and 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 expressions of UCP-1 and CD137 in 3T3-L1 cells. Conclusions: The study shows that VD3 may promote white fat beige through IL-27/P38MAPK/PGC-1α pathway.
Keywords: Vitamin D3, White fat beige, Obesity, il-27, PGC-1α, UCP-1
Received: 07 Jul 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Zhou, Shu, Zhao, Wu, He, Luy, Zhou and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yong Zhou, Department of Medical Cell Biology and Genetics, School of Basic Medical Science, Southwest Medical University, Luzhou, 646000, China, Luzhou, China
Ling Ma, Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, 646000, China, Luzhou, China
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