The effects of dietary vitamin D supplementation and in vitro 1,25 dihydroxyvitamin D3 treatment on autophagy in bone marrow-derived dendritic cells from high fat diet-induced obese mice

Author(s):  
So Jeong Kim ◽  
Da Hye Cho ◽  
Ga Young Lee ◽  
Jeong Hee An ◽  
Sung Nim Han
2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chan Yoon Park ◽  
Shuang Zhu ◽  
Young Sun Jung ◽  
Sung Nim Han

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).


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 364 ◽  
Author(s):  
Chan Yoon Park ◽  
Tae Yeon Kim ◽  
Ji Su Yoo ◽  
Yeonkyung Seo ◽  
Munkyong Pae ◽  
...  

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.


2021 ◽  
Vol 15 (6) ◽  
pp. 673
Author(s):  
Min Su Kang ◽  
Chan Yoon Park ◽  
Ga Young Lee ◽  
Da Hye Cho ◽  
So Jeong Kim ◽  
...  
Keyword(s):  
T Cells ◽  

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 796
Author(s):  
Jeong Hee An ◽  
Da Hye Cho ◽  
Ga Young Lee ◽  
Min Su Kang ◽  
So Jeong Kim ◽  
...  

Obesity is associated with an impaired balance of CD4+ T cell subsets. Both vitamin D and obesity have been reported to affect the mTOR pathway. In this study, we investigated the effects of vitamin D on CD4+ T cell subsets and the mTOR pathway. Ten-week-old male C57BL/6 mice were divided into four groups and fed diets with different fat (control or high-fat diets: CON or HFD) and vitamin D contents (vitamin D control or supplemented diets: vDC or vDS) for 12 weeks. T cells purified by negative selection were stimulated with anti-CD3/anti-CD28 mAbs and cultured for 48 h. The percentage of CD4+IL-17+ T cells was higher in the vDS than vDC groups. The CD4+CD25+Foxp3+ T cells percentage was higher in HFD than CON groups. The phospho-p70S6K/total-p70S6K ratio was lower in vDS than vDC, but the phospho-AKT/total-AKT ratio was higher in vDS than vDC groups. Hif1α mRNA levels were lower in vDS than vDC groups. These findings suggest HIF1α plays an important role in vitamin-D-mediated regulation of glucose metabolism in T cells, and dietary vitamin D supplementation may contribute to the maintenance of immune homeostasis by regulating the mTOR pathway in T cells.


2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Yu-Wen Cheng ◽  
Ze-Bei Zhang ◽  
Bei-Di Lan ◽  
Jing-Rong Lin ◽  
Xiao-Hui Chen ◽  
...  

Obesity-induced secretory disorder of adipose tissue–derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)–infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow–specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.


1960 ◽  
Vol 198 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Eugene B. Dowdle ◽  
David Schachter ◽  
Harris Schenker

The active transport of calcium from the mucosal to the serosal surfaces of everted gut-sacs of the rat is dependent on the dietary vitamin D. The active transfer in vitro is significantly increased one hour following the administration of calciferol by gastric tube to rats depleted of the vitamin. Vitamins D2 and D3 are approximately equally effective, whereas dihydrotachysterol (A.T. 10) is somewhat more effective than either of the vitamins D. Ultraviolet irradiation of intact rats also increases the active transport of calcium in vitro. Maintenance on a low calcium diet increases the active transfer, whereas thyroparathyroidectomy decreases it. Vitamin D is required to demonstrate both of these effects clearly. The results support the hypothesis that the active transfer is an adaptive mechanism which ensures adequate absorption when the requirement for calcium is increased, or when the diet is low in calcium.


2017 ◽  
Vol 4 (11) ◽  
pp. 170917 ◽  
Author(s):  
Yanyun Pan ◽  
Dandan Zhao ◽  
Na Yu ◽  
Tian An ◽  
Jianan Miao ◽  
...  

Curcumin is an active component derived from Curcuma longa L. which is a traditional Chinese medicine that is widely used for treating metabolic diseases through regulating different molecular pathways. Here, in this study, we aimed to comprehensively investigate the effects of curcumin on glycolipid metabolism in vivo and in vitro and then determine the underlying mechanism. Male C57BL/6 J obese mice and 3T3-L1 adipocytes were used for in vivo and in vitro study, respectively. Our results demonstrated that treatment with curcumin for eight weeks decreased body weight, fat mass and serum lipid profiles. Meanwhile, it lowered fasting blood glucose and increased the insulin sensitivity in high-fat diet-induced obese mice. In addition, curcumin stimulated lipolysis and improved glycolipid metabolism through upregulating the expressions of adipose triglyceride lipase and hormone-sensitive lipase, peroxisome proliferator activated receptor γ/α (PPARγ/α) and CCAAT/enhancer binding proteinα (C/EBPα) in adipose tissue of the mice. In differentiated 3T3-L1 cells, curcumin reduced glycerol release and increased glucose uptake via upregulating PPARγ and C/EBPα. We concluded that curcumin has the potential to improve glycolipid metabolism disorders caused by obesity through regulating PPARγ signalling pathway.


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