Effects of 1,25-Dihydroxyvitamin D3 on the Inflammatory Responses of Stromal Vascular Cells and Adipocytes from Lean and Obese Mice

Vitamin D status has been implicated in obesity and adipose tissue inflammation. In the present study, we explored the effects of dietary vitamin D supplementation on adipose tissue inflammation and immune cell population, and the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) treatment on pro-inflammatory cytokine production by stromal vascular cells (SVCs) and adipocytes in lean and high-fat diet-induced obese mice. The results show that epididymal fat Mcp-1 and Rantes mRNA levels, which were higher in obese mice compared with lean mice, were significantly down-regulated by vitamin D supplementation. While obese mice had higher numbers of macrophages and natural killer (NK) cells within adipose tissue, these remained unaltered by vitamin D supplementation. In accordance with these in vivo findings, the in vitro 1,25(OH)2D3 treatment decreased IL-6, MCP-1, and IL-1β production by SVCs from obese mice, but not by adipocytes. In addition, 1,25(OH)2D3 treatment significantly decreased Tlr2 expression and increased mRNA levels of Iκba and Dusp1 in SVCs. These findings suggest that vitamin D supplementation attenuates inflammatory response in adipose tissue, especially in SVCs, possibly through inhibiting NF-κB and MAPK signaling pathways in SVCs but not by the inhibition of macrophage infiltration.

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Effects of 1,25-dihydroxyvitamin D3 on Inflammatory Responses of Stromal Vascular Cells and Adipocytes from Control and Obese Mice (FS12-04-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz049.fs12-04-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Chan Yoon Park ◽

Tae Yeon Kim ◽

Yeonkyung Seo ◽

Ji Su Yoo ◽

Munkyong Pae ◽

...

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

T Cell ◽

Immune Cells ◽

Inflammatory Cytokine ◽

Nk Cell ◽

Vitamin D Supplementation ◽

Mrna Levels ◽

Dihydroxyvitamin D3

Abstract Objectives Several in vitro studies showed that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment could inhibit chronic inflammation in mouse or human adipocytes; however there have been a few in vivo studies. We investigated whether vitamin D supplementation affects subpopulation of immune cells in adipose tissue and the effects of in vitro 1,25(OH)2D3 treatment on pro-inflammatory cytokine secretion by stromal vascular cells (SVC) and adipocytes. Methods Five-wk old C57BL/6 N mice were divided into 4 groups and fed diets differ in fat amount (10 or 45% kcal fat: CON or HFD) and vitamin D content (1000 or 10,000 IU/kg of diet: DC, or DS) for 13 wks. Subpopulation of immune cells (macrophage, NK cell, CD 4 T cell, CD 8 T cell, B cell) from adipose tissue-derived SVC was determined by FACS analysis. Five-wk old C57BL/6 mice were fed control or HFD diets (10 or 60% kcal fat, CON or HFD) for 12 wks. Adipocytes and SVC, isolated from visceral adipose tissue, were cultured with or without 10 nM of 1,25(OH)2D3 for 48 h and stimulated with LPS during the last 24 h. Pro-inflammatory cytokines produced by SVC and adipocytes were measured by ELISA. The mRNA levels of Tlr2, Tlr4, Dusp1, and Dusp10 were determined in SVC by real-time PCR. Results The number of macrophages and NK cells within adipose tissue were higher in the HFD groups than CON groups. Dietary vitamin D did not alter the number of immune cells in adipose tissue. The production of IL-6 and MCP-1 from SVC and adipocytes were higher in the HFD groups compared with CON groups. In vitro 1,25(OH)2D3 treatment decreased IL-6, MCP-1, IL-1β production by SVC from HFD group and decreased IL-6 production by SVC from CON group. SVC Tlr2 mRNA levels, which were higher in the HFD group, decreased significantly by in vitro 1,25(OH)2D3 treatment. mRNA levels of Dusp1, which inhibits MAPK signaling, were increased by in vitro 1,25(OH)2D3 treatment. However, pro-inflammatory cytokine secretion from adipocytes was not affected by in vitro 1,25(OH)2D3 treatment. Conclusions Although vitamin D supplementation did not reduce macrophage and NK cell numbers in adipose tissue, 1,25(OH)2D3 seemed to decrease pro-inflammatory cytokine production from SVCs by regulating Tlr2 and Dusp1. Funding Sources Supported by the grant from the National Research Foundation (NRF) of Korea (NRF-2018R1D1A1B070491).

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Effects of Vitamin D Supplementation on 1, 25-dihydroxyvitamin D Metabolism and Its Impact on Adipose Tissue Inflammation in Obese Mice (P24-004-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p24-004-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Chan Yoon Park ◽

Shuang Zhu ◽

Young Sun Jung ◽

Sung Nim Han

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Vitamin D Supplementation ◽

Dietary Vitamin ◽

Epididymal Adipose Tissue ◽

Mrna Levels ◽

Obese Mice ◽

Dihydroxyvitamin D ◽

Vitamin D Levels ◽

Dietary Vitamin D

Abstract Objectives Adipose tissue expresses CYP27B1 and VDR, suggesting local metabolism and function of 1,25-dihydroxyvitamin D (1,25(OH)2D) in adipose tissue. Obesity has been associated with dysregulation of 1,25(OH)2D levels. We investigated effects of vitamin D supplementation on 1,25(OH)2D metabolism and its impact in adipose tissue of obese mice. Methods Six-wk-old C57BL/6 mice were divided into 4 groups and fed experimental diets containing 10% or 45% kcal fat (CON or HFD) and differing in vitamin D content (1000 or 25,000 IU/kg of diet, DC or DS) for 13 wks. Serum 1,25(OH)2D and PTH levels were determined with radio- or enzyme-immunoassay. The mRNA levels of Cyp27b1, Cyp24a1, and Lrp2 in the kidney, and Cyp27b1, Vdr, and pro-inflammatory cytokines (Mcp-1, Rantes, Mip-1γ, Tnf-α, Il-6, Il-1β, and Ifn-γ) in the epididymal adipose tissue were determined by real-time PCR. Results Overall, serum 1,25(OH)2D levels were higher in DS groups compared with DC groups. When 1,25(OH)2D levels were compared between CON and HFD groups, differential pattern was observed depending on vitamin D levels in the diet. HFD-DC group showed higher serum 1,25(OH)2D and PTH levels compared with CON-DC group. However, in the DS groups, serum 1,25(OH)2D and PTH levels were not significantly affected by dietary fat amount. Renal Cyp24a1 mRNA levels, which could be up-regulated by dietary vitamin D, was higher in CON-DS group compared with CON-DC group. However, in the HFD groups, renal Cyp24a1 mRNA levels were similar in DC and DS groups. Mcp-1 and Rantes mRNA levels were higher in the HFD groups compared with CON groups, and their overall expression levels were down-regulated by vitamin D supplementation. Overall, mRNA levels of Il-6 and Il-1β were lower in the DS groups compared with DC groups. Conclusions Dietary vitamin D supplementation alleviated inflammatory responses in adipose tissue. Both 1,25(OH)2D in circulation and locally produced 1,25(OH)2D in adipose tissue might have contributed to the effect. Funding Sources Supported by the grant from the National Research Foundation (NRF) of Korea (NRF-2018R1D1A1B070491).

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Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice

Nutrients ◽

10.3390/nu12020342 ◽

2020 ◽

Vol 12 (2) ◽

pp. 342 ◽

Cited By ~ 2

Author(s):

Alexandra Marziou ◽

Clothilde Philouze ◽

Charlène Couturier ◽

Julien Astier ◽

Philippe Obert ◽

...

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

De Novo ◽

De Novo Lipogenesis ◽

Acid Oxidation ◽

Mrna Levels ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Triglyceride Accumulation

The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect of VD supplementation on obesity and associated disorders was evaluated in high-fat- and high-sucrose (HFS)-fed mice. Morphological, histological, and molecular phenotype were characterized. The increased body mass and adiposity caused by HFS diet as well as fat cell hypertrophy and glucose homeostasis were not improved by VD supplementation. However, VD supplementation led to a decrease of HFS-induced inflammation in inguinal adipose tissue, characterized by a decreased expression of chemokine mRNA levels. Moreover, a protective effect of VD on HFS-induced hepatic steatosis was highlighted by a decrease of lipid droplets and a reduction of triglyceride accumulation in the liver. This result was associated with a significant decrease of gene expression coding for key enzymes involved in hepatic de novo lipogenesis and fatty acid oxidation. Altogether, our results show that VD supplementation could be of interest to blunt the adipose tissue inflammation and hepatic steatosis and could represent an interesting nutritional strategy to fight obesity-associated comorbidities.

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Intestinal vitamin D receptor modulates lipid metabolism, adipose tissue inflammation and liver steatosis in obese mice

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2019.03.007 ◽

2019 ◽

Vol 1865 (6) ◽

pp. 1567-1578 ◽

Cited By ~ 6

Author(s):

Daniel Jahn ◽

Donata Dorbath ◽

Anne-Kristin Schilling ◽

Lisa Gildein ◽

Chantal Meier ◽

...

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Lipid Metabolism ◽

Vitamin D Receptor ◽

Liver Steatosis ◽

Adipose Tissue Inflammation ◽

Obese Mice ◽

Tissue Inflammation

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Regulation of adipose tissue inflammation by adenosine 2A receptor in obese mice

Journal of Endocrinology ◽

10.1530/joe-18-0169 ◽

2018 ◽

Vol 239 (3) ◽

pp. 365-376 ◽

Cited By ~ 4

Author(s):

Ya Pei ◽

Honggui Li ◽

Yuli Cai ◽

Jing Zhou ◽

Xianjun Luo ◽

...

Keyword(s):

Adipose Tissue ◽

Protective Role ◽

Mrna Levels ◽

Adipose Tissue Inflammation ◽

Necrosis Factor Alpha ◽

Tissue Inflammation ◽

Akt Phosphorylation ◽

The Status ◽

Adenosine 2A Receptor

Adenosine 2A receptor (A2AR) exerts anti-inflammatory effects. However, the role of A2AR in obesity-associated adipose tissue inflammation remains to be elucidated. The present study examined the expression of A2AR in adipose tissue of mice with diet-induced obesity and determined the effect of A2AR disruption on the status of obesity-associated adipose tissue inflammation. WT C57BL/6J mice and A2AR-disrupted mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and adipose tissue inflammation. In vitro, bone marrow-derived macrophages from A2AR-disrupted mice and WT control mice were treated with palmitate and examined for macrophage proinflammatory activation. Compared with that of low-fat diet (LFD)-fed WT mice, A2AR expression in adipose tissue of HFD-fed WT mice was increased significantly and was present predominantly in adipose tissue macrophages. The increase in adipose tissue A2AR expression in HFD-fed mice was accompanied with increased phosphorylation states of c-Jun N-terminal kinase 1 p46 and nuclear factor kappa B p65 and mRNA levels of interleukin (Il)-1beta, Il6 and tumor necrosis factor alpha. In A2AR-disrupted mice, HFD feeding induced significant increases in adipose tissue inflammation, indicated by enhanced proinflammatory signaling and increased proinflammatory cytokine expression, and adipose tissue insulin resistance, indicated by a decrease in insulin-stimulated Akt phosphorylation relative to those in WT mice. Lastly, A2AR disruption enhanced palmitate-induced macrophage proinflammatory activation. Taken together, these results suggest that A2AR plays a protective role in obesity-associated adipose tissue inflammation, which is attributable to, in large part, A2AR suppression of macrophage proinflammatory activation.

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