scholarly journals Vitamin D Receptor Gene Expression in Adipose Tissue of Obese Individuals is Regulated by miRNA and Correlates with the Pro-Inflammatory Cytokine Level

2019 ◽  
Vol 20 (21) ◽  
pp. 5272 ◽  
Author(s):  
Marta Izabela Jonas ◽  
Alina Kuryłowicz ◽  
Zbigniew Bartoszewicz ◽  
Wojciech Lisik ◽  
Maurycy Jonas ◽  
...  

Background: Given the role that vitamin D (VD) plays in the regulation of the inflammatory activity of adipocytes, we aimed to assess whether obesity changes the expression of VD-related genes in adipose tissue and, if so, to investigate whether this phenomenon depends on microRNA interference and how it may influence the local inflammatory milieu. Methods: The expression of genes encoding VD 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and receptor (VDR), selected interleukins and microRNAs was evaluated by real-time PCR in visceral (VAT) and in subcutaneous (SAT) adipose tissues of 55 obese (BMI > 40 kg/m2) and 31 normal-weight (BMI 20–24.9 kg/m2) individuals. Results: VDR mRNA levels were higher, while CYP27B1 levels were lower in adipose tissues of obese patients than in those of normal-weight controls (VAT: P = 0.04, SAT: P < 0.0001 and VAT: P = 0.004, SAT: P = 0.016, respectively). The expression of VDR in VAT of obese subjects correlated negatively with levels of miR-125a-5p (P = 0.0006, rs = −0.525), miR-125b-5p (P = 0.001, rs = −0.495), and miR-214-3p (P = 0.009, rs = −0.379). Additionally, VDR mRNA concentrations in visceral adipose tissues of obese subjects correlated positively with mRNA levels of interleukins: 1β, 6 and 8. Conclusions: We observed obesity-associated up-regulation of VDR and down-regulation of CYP27B mRNA levels in adipose tissue. VDR expression correlates with the expression of pro-inflammatory cytokines and may be regulated by miRNAs.

2012 ◽  
Vol 7 (2) ◽  
pp. 192-200
Author(s):  
Jacek Turyn ◽  
Adriana Mika ◽  
Piotr Stepnowski ◽  
Julian Swierczynski

AbstractIt is generally accepted that the location of body fat deposits may play an important role in the risk of developing some endocrine and metabolic diseases. We have studied the effect of food restriction and food restriction/refeeding, often practiced by individuals trying to lose body weight, on the expression of genes which are associated with obesity and certain metabolic disorders in inguinal, epididymal, and perirenal rat white adipose tissues. Gene expression was analyzed by real time semi-quantitative polymerase chain reaction and by Western blot. We found that prolonged food restriction caused a significant decrease of body and adipose tissue mass as well as the increase of Scd1 and Elovl6 gene expressions in all main rat adipose tissue deposits. Food restriction/refeeding caused increases of: a) Scd1 and Elovl6 mRNA levels in adipose tissue, b) Scd1 protein level and c) desaturation index in adipose tissue. The increased expression of both genes was unusually high in inguinal adipose tissue. The results suggest that the increase of Scd1 and Elovl6 gene expressions in white adipose tissue by prolonged food restriction and prolonged food restriction/refeeding may contribute to accelerated fat recovery that often occurs in individuals after food restriction/refeeding.


2002 ◽  
Vol 282 (1) ◽  
pp. E46-E51 ◽  
Author(s):  
Frédérique Diraison ◽  
Eric Dusserre ◽  
Hubert Vidal ◽  
Monique Sothier ◽  
Michel Beylot

To determine whether increased lipogenesis contributes to human obesity, we measured (postabsorptive state), in lean and obese subjects, lipid synthesis (deuterated water method) and the mRNA concentration (RT-competitive PCR) in subcutaneous adipose tissue of fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1c. Before energy restriction, obese subjects had an increased contribution of hepatic lipogenesis to the circulating triglyceride pool (14.5 ± 1.3 vs. 7.5 ± 1.9%, P < 0.01) without enhancement of cholesterol synthesis. This increased hepatic lipogenesis represented an excess of 2–5 g/day of triglycerides, which would represent 0.7–1.8 kg on a yearly basis. The lipogenic capacity of adipose tissue appeared, on the contrary, decreased with lower FAS mRNA levels ( P < 0.01) and a trend for decreased SREBP-1c mRNA ( P = 0.06). Energy restriction in obese patients decreased plama insulin ( P < 0.05) and leptin ( P < 0.05) and normalized hepatic lipogenesis. FAS mRNA levels were unchanged, whereas SREBP-1c increased. In conclusion, subjects with established obesity have an increased hepatic lipogenesis that could contribute to their excessive fat mass but no evidence for an increased lipogenic capacity of adipose tissue.


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).


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chan Yoon Park ◽  
Yongho Shin ◽  
Jeong-Han Kim ◽  
Sung Nim Han

Abstract Objectives Vitamin D deficiency is often observed in obese person. One of the mechanisms suggested is the decreased bioavailability of vitamin D due to its deposition in adipose tissue. We investigated the effects of obesity on vitamin D distribution by measuring 25(OH)D levels in circulation and comparing vitamin D content in liver and adipose tissue from obese and control mice fed different levels of vitamin D. Methods Six-wk-old C57BL/6 mice were fed control or high fat (10 or 45% kcal fat, CON or HFD) diets containing different levels of vitamin D3 (1000, or 25,000 IU/kg of diet, CVd or HVd) for 13 wks. Serum 25-hydroxyvitamin D (25(OH)D) level was determined by radioimmunoassay. Vitamin D3 and 25(OH)D3 levels in the liver and epididymal adipose tissue (AT) were quantified by LC-MS/MS. mRNA levels of liver Cyp2r1 and Cyp27a1 were determined by real-time PCR. Results Overall, serum 25(OH)D levels were significantly higher in the HVd groups compared with CVd groups. There was no difference in serum 25(OH)D levels between CON-CVd and HFD-CVd groups. However, in the vitamin D supplemented groups, HFD-HVd group had significantly lower serum 25(OH)D levels (20% lower) than CON-HVd group. Vitamin D3 levels in the liver and AT were 55 and 100 times higher in the HVd groups (liver and AT: 719 and 318 ng/g tissue) compared with the CVd groups. 25(OH)D3 levels in the liver and AT were also 3.3 and 2.4 times higher in the HVd groups (liver and AT: 33.9 and 18.9 ng/g tissue) than those of the CVd groups. Total amount of vitamin D3 in the liver and AT were significantly higher in the HFD-HVd group (121 and 44% higher) compared with CON-HVd group. However, when mice were fed the control levels of vitamin D, dietary fat levels did not affect the vitamin D3 amount in the liver and AT. Liver Cyp2r1 and Cyp27a1 mRNA levels did not differ among groups. Conclusions When vitamin D intake was at a supplementation level, a significant amount of dietary vitamin D seemed to be stored in the liver and AT; thus excess body adiposity could contribute to lower serum 25(OH)D level. However, at a control level of vitamin D intake, obesity did not affect tissue vitamin D amount and serum 25(OH)D levels. Funding Sources Supported by the grant from the National Research Foundation (NRF) of Korea (NRF-2018R1D1A1B070491) and Research Grant from Research Affairs at Seoul National University.


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 342 ◽  
Author(s):  
Alexandra Marziou ◽  
Clothilde Philouze ◽  
Charlène Couturier ◽  
Julien Astier ◽  
Philippe Obert ◽  
...  

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.


2020 ◽  
Vol 21 (23) ◽  
pp. 9091
Author(s):  
Valentina Ceccarelli ◽  
Ilaria Barchetta ◽  
Flavia Agata Cimini ◽  
Laura Bertoccini ◽  
Caterina Chiappetta ◽  
...  

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes’ size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02–1.9; χ2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76–1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.


2008 ◽  
Vol 158 (3) ◽  
pp. 333-341 ◽  
Author(s):  
T Lappalainen ◽  
M Kolehmainen ◽  
U Schwab ◽  
L Pulkkinen ◽  
D E Laaksonen ◽  
...  

ObjectiveSerum amyloid A (SAA) is a novel link between increased adipose tissue mass and low-grade inflammation in obesity. Little is known about the factors regulating its serum concentration and mRNA levels. We investigated the association between SAA and leptin in obese and normal weight subjects and analyzed the effect of weight reduction on serum SAA concentration and gene expression in adipose tissue of the obese subjects.MethodsSeventy-five obese subjects (60±7 years, body mass index (BMI) 32.9±2.8 kg/m2, mean±s.d.) with impaired fasting plasma glucose or impaired glucose tolerance and other features of metabolic syndrome, and 11 normal weight control subjects (48±9 years, BMI 23.7±1.9 kg/m2) were studied at the baseline. Twenty-eight obese subjects underwent a 12-week intensive weight reduction program followed by 5 months of weight maintenance. Blood samples and abdominal s.c. adipose tissue biopsies were taken at the baseline and after the follow-up. Gene expression was studied using real-time quantitative PCR.ResultsThe gene expressions in women and serum concentrations of leptin and SAA were interrelated independently of body fat mass in the obese subjects (r=0.54, P=0.001; r=0.24, P=0.039 respectively). In multiple linear regression analyses, leptin mRNA explained 38% of the variance in SAA mRNA (P=0.002) in the obese women. Weight loss of at least 5% increased SAA mRNA expression by 48 and 36% in men and women, but serum SAA concentrations did not change.ConclusionsThe association between SAA and leptin suggests an interaction between these two adipokines, which may have implications in inflammatory processes related to obesity and the metabolic syndrome.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Maha H. Daghestani ◽  
Arjumand Warsy ◽  
Mazin H. Daghestani ◽  
Ali N. Al-odaib ◽  
Abdelmoneim Eldali ◽  
...  

Background. Several studies have shown an association between codon 16 polymorphism of theβ2AR gene and obesity.Methods. We studied the association between Arg16Gly polymorphism and obesity and its influence on anthropometric parameters, lipids, insulin resistance and leptin in Saudi individuals. The study group included 329 individuals (males: 109 and females: 220). Metabolic parameters, including glucose, lipids, insulin, and leptin were analyzed and anthropometric parameters including waist and hip circumference, waist/hip (W/H) ratio, and body mass index (BMI) were measured and HOMA-IR was calculated. Genotyping was conducted by DNA sequencing of 353 bp fragments, carrying the Arg16Gly polymorphic site.Results and Conclusion. Overweight and obese subjects had a significantly higher frequency of Gly16 (0.375 and 0.38, resp.) compared with normal-weight subjects (0.200). In addition, subjects carrying Gly16 allele regardless of their BMI had greater waist and hip circumference, W/H ratio, plasma lipids, leptin, glucose level, and insulin resistance as judged from the HOMA-IR, compared to those with the wild-type allele. The findings of this study show a significant association between the Arg16Gly polymorphism inβ2AR gene and the development of insulin resistance, overweight, and obesity in Saudi populations with an influence on the levels of lipid and leptin.


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