Progranulin serum levels and gene expression in subcutaneous vs visceral adipose tissue of severely obese patients undergoing bariatric surgery

2019 ◽  
Vol 91 (3) ◽  
pp. 400-410 ◽  
Author(s):  
Judith Brock ◽  
Andreas Schmid ◽  
Thomas Karrasch ◽  
Petra Pfefferle ◽  
Jutta Schlegel ◽  
...  
2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 245-247
Author(s):  
S Keshavjee ◽  
J Yadav ◽  
K Schwenger ◽  
S Fischer ◽  
T D Jackson ◽  
...  

Abstract Background Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis (SS) and nonalcoholic steatohepatitis (NASH). It affects 74–98% of individuals with morbid obesity undergoing bariatric surgery (BSX). Among several factors contributing to NAFLD pathogenesis, adipokines secreted by visceral adipose tissue (VAT) can play a role by regulating glucose/lipid metabolism and inflammation. Aims This study aims to determine if visceral adipose tissue adipokine and cytokine gene expression are associated with NAFLD (SS and NASH) at the time of BSX. Methods Patients were recruited from the Toronto Western Hospital Bariatric Clinic. Demographic data was recorded. The VAT and liver biopsies were collected at the time of bariatric surgery. VAT adipokines and other mediators were assessed by RT-PCR and included markers of thermogenic capacity, inflammation, fibrosis, adipokines, and others. Liver histology was assessed by a pathologist using the Brunt system and individuals were diagnosed as either SS, NASH, or having a healthy liver (HL). Blood samples were collected pre-BSX to measure liver and metabolic syndrome related parameters, including HOMA-IR, HbA1c, liver enzymes, and lipid profile. Anthropometry was also assessed. Groups were compared using Kruskal-Wallis test followed by Wilcoxon ranked sum, or chi-square and Fisher’s exact test as necessary. Data was considered to be statistically significant with a p-value less than 0.05. Results We are presenting data on 126 patients, 80.2% females with a median age of 49 and a body mass index (BMI) of 46.9. Fifty-seven patients had SS, 34 had NASH and 35 had a healthy liver (HL). BMI, age, and sex did not differ between the three groups. First, we found that those with NASH had significantly higher VAT expression of fibrosis (Loxl2), inflammation (CCL4 and TGFb1) and proliferation markers (E2F1) and significantly lower expression of adipokines (TNFa and resistin) compared to HL. Also, we found that SS had significantly higher fibrosis (Col3a1, Col6a1, Loxl2, CD9 and Acta2), inflammation (Nox2, TGFb1, IFNg and Clec10a), browning (PPARa, PPARg and Glut1) and proliferation (E2F1) marker expression compared to HL. Conclusions Results show that there is a significant difference in the expression pattern of VAT fibrotic and inflammatory markers between HL, SS and NASH patients. The observed increase of inflammatory markers in NAFLD is in line with prior research outlining the ability of inflammatory mediators from VAT to contribute to liver pathology via portal circulation. The relationship between VAT characteristics and NAFLD are important in understanding the widespread metabolic effects of obesity. Funding Agencies CIHRCanadian Liver foundation


2014 ◽  
Vol 99 (1) ◽  
pp. E53-E61 ◽  
Author(s):  
Julie Lasselin ◽  
Eric Magne ◽  
Cédric Beau ◽  
Patrick Ledaguenel ◽  
Sandra Dexpert ◽  
...  

Context: The inflammatory state of the adipose tissue is believed to contribute to systemic low-grade inflammation in obesity. Objective: This study assessed the relationship between adipose and circulating inflammatory markers as well as the influence of adipose inflammation on bariatric surgery-induced weight reduction. Design: This was a cross-sectional and longitudinal study (up to 14 mo). Setting: The study was conducted in the digestive/bariatric surgery department of the Tivoli and Jean Villar clinics, Bordeaux, France. Patients: Thirty-seven obese patients [body mass index (BMI) > 35–40 kg/m2)] seeking bariatric surgery were included. Twenty-eight of them were successively followed up at 1–3 months after surgery and 25 between 6 and 14 months after surgery. Main Outcome Measures: Fasting serum samples were collected before surgery to assess concentrations of inflammatory markers. Samples of visceral adipose tissue were extracted during surgery and gene expression of cytokines and immune cell markers were evaluated using quantitative RT-PCR. Pre- and postsurgery weight and BMI were collected. Results: Gene expression of several cytokines were strongly intercorrelated in the visceral adipose tissue. Adipose expression of macrophage and T cell markers were related to adipose expression of TNF-α and IL-1 receptor antagonist (P < .01) and to systemic levels of TNF-α (P < .01) and IL-6 (P < .05). A higher inflammatory state of the adipose tissue predicted a lower BMI reduction after surgery (P < .05), notably at early stages after surgery. Conclusions: These findings support the involvement of macrophages and T cells in adipose inflammation and provide new information regarding the role of the visceral adipose tissue in the inflammatory state of obesity and its impact on obesity treatment outcomes, such as surgery-induced weight loss.


2014 ◽  
Vol 46 ◽  
pp. 627-628
Author(s):  
Tamara E. Carver ◽  
Robert Bracewell ◽  
Olivier Babineau ◽  
Olivier Court ◽  
Ross E. Andersen

2007 ◽  
Vol 17 (7) ◽  
pp. 934-940 ◽  
Author(s):  
Josiane Woutheres Bortolotto ◽  
Rogério Margis ◽  
Ângela Cristine Bersch Ferreira ◽  
Alexandre Vontobel Padoin ◽  
Cláudio Cora Mottin ◽  
...  

2014 ◽  
Vol 46 (7) ◽  
pp. 1462-1465 ◽  
Author(s):  
TAMARA E. CARVER ◽  
OLIVIER COURT ◽  
NICOLAS V. CHRISTOU ◽  
RYAN E. R. REID ◽  
ROSS E. ANDERSEN

2010 ◽  
Vol 7 (4) ◽  
pp. 20-23
Author(s):  
A V Kosygina ◽  
V V Sosunov ◽  
V A Peterkova ◽  
I I Dedov

The aim of this study was to investigate the characteristics of visfatin - PBEF1 - gene expression in subcutaneous and visceral adipose tissue and serum levels of visfatin in children with relation to age and anthropometric parameters. The study included 52 patients (27 boys (52%), 25 girls (48%) aged from 2,5 to 18 years (13,8 [7,4-15,1] years)), who underwent an elective surgical intervention. PBEF1 mRNA level was measured by real-time PCR and serum level of visfatin was quantified by immunoenzyme assay. According to our study visfatin serum concentration in children with normal body weight was 9,2 [7,4-11,6] ng/ml, whereas in the overweight group - 9,5 [7,5-11,1] ng/ml (p=0,5). No statistically significant gender difference in serum visfatin levels was observed. No correlation between visfatin levels and age, pubertal stages and anthropometric indices in children was found. Statistically significant differences in the level of gene expression between subcutaneous and visceral adipose tissue were found (р=0,002) in the total group of children surveyed and children with normal weight, while there were no depot-specific differences in overweight children. The study did not reveal any dependence of PBEF1 expression on age and sex of children. Expression of PBEF1 in adipose tissue decreases with puberty (PBEF1VATγ=-0,24, р=0,02; PBEF1SATγ=-0,25, р=0,02). PBEF1 expression in adipose tissue was not correlated with the serum visfatin (R=-0,06, р=0,6).


2020 ◽  
Vol 25 (5) ◽  
pp. 568-576
Author(s):  
L. B. Vasileva ◽  
M. S. Artemyeva ◽  
Yi. Ma ◽  
K. A. Kondratov ◽  
A. D. Anopova ◽  
...  

Objective. To determine the effect of morbid obesity, impaired carbohydrate metabolism and bariatric surgery on adiponectin and leptin mRNA levels in subcutaneous and visceral adipose tissue.Design and methods. The study included 30 obese female patients. Eleven patients had co-existent impaired carbohydrate metabolism. The control group consisted of 10 healthy non-obese women. In all obese patients, subcutaneous and visceral adipose tissue samples were taken during bariatric surgery. In obese patients 1 year after the intervention and in control individuals subcutaneous adipose tissue samples were collected. The circulating levels of adiponectin and leptin were determined by the enzyme immunoassay. The amount of adiponectin and leptin mRNA in adipose tissue were analyzed by real-time polymerase chain reaction.Results. During the first postoperative year, all patients showed a monotonous decrease in body mass index. After the surgery, the circulating levels of adiponectin and leptin returned to reference values (for healthy population). Compared with the control group, obese patients showed 1,4-times lower adiponectin mRNA level (p < 0,01) in subcutaneous adipose tissue, while leptin mRNA level did not change. In obese patients with impaired carbohydrate metabolism, the adiponectin mRNA level was twice lower in visceral adipose tissue (p < 0,01), compared to patients without impaired carbohydrate metabolism. In obese patients with and without impaired carbohydrate metabolism, mRNA levels of adipokines were more than 2-times lower in visceral adipose tissue compared to subcutaneous adipose tissue (p < 0,05). In subcutaneous adipose tissue, 1 year after bariatric intervention, adiponectin mRNA level decreases by 4,5 times (p < 0,01) in obese patients, and leptin mRNA level decreases by 3,1 times (p < 0,01) in patients with obesity and by 1,5 times (p < 0,05) in patients with obesity and impaired carbohydrate metabolism. Neither adiponectin nor leptin mRNA levels from adipose tissue of different localization showed statistically significant correlation. No correlation was found between the levels of circulating adipokines and their mRNA amount in adipose tissue.Conclusions. Our results indicate that adiponectin and leptin mRNA levels in adipose tissue cells depend on their localization in the body, as well as the presence of obesity and impaired carbohydrate metabolism. We also showed that adiponectin and leptin mRNA levels in adipose tissue change in response to bariatric surgery.


2015 ◽  
Vol 28 (5) ◽  
pp. 583-590 ◽  
Author(s):  
Alexander Schaudinn ◽  
Nicolas Linder ◽  
Nikita Garnov ◽  
Felix Kerlikowsky ◽  
Matthias Blüher ◽  
...  

Author(s):  
Gabriel Wagner ◽  
Anna Fenzl ◽  
Josefine Lindroos-Christensen ◽  
Elisa Einwallner ◽  
Julia Husa ◽  
...  

Abstract Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. Key messages LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.


Metabolism ◽  
2011 ◽  
Vol 60 (12) ◽  
pp. 1775-1780 ◽  
Author(s):  
René Baudrand ◽  
José Miguel Domínguez ◽  
Cristian A. Carvajal ◽  
Arnoldo Riquelme ◽  
Carmen Campino ◽  
...  

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