Active non-alcoholic steatohepatitis and severe fibrosis are associated to dysfunctional adipose tissue and worsen with adipose tissue insulin resistance independently of body mass index

2020 ◽  
Vol 73 ◽  
pp. S110-S111
Author(s):  
Luisa Vonghia ◽  
Melania Gaggini ◽  
An Verrijken ◽  
Jonas Weyler ◽  
Fabrizia Carli ◽  
...  
2009 ◽  
Vol 94 (11) ◽  
pp. 4499-4507 ◽  
Author(s):  
David M. Selva ◽  
Albert Lecube ◽  
Cristina Hernández ◽  
Juan A. Baena ◽  
José M. Fort ◽  
...  

Context: Zinc-α2 glycoprotein (ZAG) has been proposed as a new candidate in the pathogenesis of obesity, but most of the information stems from studies performed in rodents and in vitro assays. Objective: The main aim of the study was to compare serum levels of ZAG and its expression (mRNA levels and protein) in adipose tissue and the liver between obese and nonobese subjects. The relationship between ZAG and insulin resistance was also explored. Design: This was a case-control study. Setting: The study was conducted at a university referral center. Patients and Methods: Samples of serum, sc adipose tissue (SAT), visceral adipose tissue (VAT), and liver were obtained from 20 obese subjects during bariatric surgery. Samples from 10 nonobese patients matched by age and gender were used as a control group. Serum ZAG levels were determined by ELISA. ZAG mRNA levels were measured by real-time PCR and protein content by Western blot. The effect of insulin on liver production of ZAG was assessed using HepG2 cultures. Results: Serum concentration of ZAG (micrograms per milliliter) was significantly lower in obese subjects (40.87 ± 10.45 vs. 63.26 ± 16.40; P = 0.002). ZAG expression was significantly lower in the adipose tissue (SAT and VAT) and liver of obese patients than in control subjects. Significant negative correlations between body mass index and circulating ZAG (r = −0.65, P < 0.001) as well as between body mass index and mRNA ZAG levels in SAT (r = −0.68, P < 0.001) and VAT were detected (r = −0.64, P < 0.001). No relationship was found between ZAG and homeostasis model assessment for insulin resistance and insulin had no effect on ZAG production in vitro. Conclusion: A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance. A downregulation of zinc-α2 glycoprotein in adipose tissue and liver exists in obese patients, and it is unrelated to insulin resistance.


Author(s):  
Vita Silvana ◽  
Andon Hestiantoro ◽  
Muharam Natadisastra ◽  
Kanadi Sumapraja ◽  
Budi Wiweko

Objective: To determine whether visceral adipose tissue or serum RBP-4 were related with the risk increment of insulin resistance in normal BMI PCOS patients. Methods: This was a cross-sectional study conducted in normal body mass index PCOS patients at Yasmin Clinic, RSCM, Jakarta from July 2014 until March 2015. Diagnosis of PCOS was established using Rotterrdam (2003) criteria. Insulin resistance was confirmed by using ratio of HOMA-IR >1.4. Results: Among 40 subjects, 20 subjects (50%) belong insulin resistance group. Serum RBP-4 level was higher in insulin resistance group (p=0.06). After ROC analysis was conducted, area under curve for of serum RBP-4 was 69.9% (CI 95% -3754.77 - (186.60-7696.14, p=0.061)). Cut-off level of serum RBP-4 was 23814.5 ng/mL yielded sensitivity and specificity to a level of 60% and 60%, respectively. After logistic regression were analyzed, visceral adipose tissue demonstrated substantial association with the risk increment of insulin resistance in normal BMI PCOS patients. Conclusions: Visceral adipose tissue demonstrated substantial association with the risk increment of insulin resistance in normal BMI PCOS patients, independent with serum RBP-4 levels. Key words: body mass index, diagnosis, insulin resistance, PCOS, retinol binding protein-4   Abstrak Tujuan: Untuk menentukan apakah jaringan adiposa viseral atau serum RBP-4 berhubungan dengan peningkatan risiko resistensi insulin pada Sindrom Ovarium Polikistik dengan indeks masa tubuh normal. Metode: Studi potong lintang dilakukan pada subjek SOPK dengan IMT normal di Klinik Yasmin, RSCM, Jakarta sejak Juli 2014 sampai dengan Maret 2015. Penegakan diagnosis SOPK dilakukan dengan kriteria Rotterdam (2003). Resistensi insulin dikonfirmasi dengan pemeriksaan rasio HOMA-IR > 1.4 Hasil: Diantara 40 subjek, sebanyak 20 subjek (50%) mengalami resistensi insulin. Kadar serum RBP-4 lebih tinggi pada kelompok resistensi insulin (p=0.06). Setelah dilakukan analisis Receiver Operating Curve (ROC), serum RBP-4 memiliki Area Under the Curve  (AUC) sebesar 69.9% (IK 95% -3754.77 - (186.60-7696.14, p=0,061)). Titik potong kadar serum RBP-4 adalah 23814.5 ng/mL dengan sensitivitas dan spesifisitas masing-masing 60% dan 60%. Setelah dilakukan analisis regresi logistik, jaringan adiposa viseral menunjukan asosiasi yang kuat dengan terjadinya resistensi insulin pada pasien SOPK dengan IMT normal. Kesimpulan: Jaringan adiposa viseral menunjukan asosiasi yang kuat dengan terjadinya resistensi insulin pada SOPK dengan IMT normal, independen terhadap kadar serum RBP-4. Kata kunci: diagnosis, indeks masa tubuh, resistensi insulin, retinol binding protein-4, SOPK


2019 ◽  
Vol 104 (10) ◽  
pp. 4552-4562 ◽  
Author(s):  
Juan R Acosta ◽  
Beatriz Tavira ◽  
Iyadh Douagi ◽  
Agné Kulyté ◽  
Peter Arner ◽  
...  

Abstract Objective Although IL-10 is generally considered as an anti-inflammatory cytokine, it was recently shown to have detrimental effects on insulin sensitivity and fat cell metabolism in rodents. Whether this also pertains to human white adipose tissue (hWAT) is unclear. We therefore determined the main cellular source and effects of IL-10 on human adipocytes and hWAT-resident immune cells and its link to insulin resistance. Methods Associations between hWAT IL-10 production and metabolic parameters were investigated in 216 participants with large interindividual variations in body mass index and insulin sensitivity. Adipose cells expressing or secreting IL-10 and the cognate IL-10 receptor α (IL10RA) were identified by flow cytometry sorting. Effects on adipogenesis, lipolysis, and inflammatory/metabolic gene expression were measured in two human primary adipocyte models. Secretion of inflammatory cytokines was investigated in cultures of IL-10–treated hWAT macrophages and leukocytes by Luminex analysis (Luminex Corp.). Results IL-10 gene expression and protein secretion in hWAT correlated positively with body mass index (BMI) and homeostasis model assessment-insulin resistance (HOMA-IR). Gene expression analyses in mature fat cells and flow cytometry–sorted hWAT-resident adipocyte progenitors, macrophages, and leukocytes demonstrated that the expression of IL-10 and the IL10RA were significantly enriched in proinflammatory M1 macrophages. In contrast to murine data, functional studies showed that recombinant IL-10 had no effect on adipocyte phenotype. In hWAT-derived macrophages and leukocytes, it induced an anti-inflammatory profile. Conclusion In hWAT, IL-10 is upregulated in proinflammatory macrophages of obese and insulin-resistant persons. However, in contrast to findings in mice, IL-10 does not directly affect human adipocyte function.


2011 ◽  
Vol 7 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Olga T. Hardy ◽  
Richard A. Perugini ◽  
Sarah M. Nicoloro ◽  
Karen Gallagher-Dorval ◽  
Vishwajeet Puri ◽  
...  

2019 ◽  
Vol 4 (6) ◽  
pp. 150-156
Author(s):  
M. M. Kochuieva ◽  
◽  
V. G. Psarova ◽  
N. M. Kyrychenko ◽  
L. A. Ruban ◽  
...  

2010 ◽  
Vol 63 (9-10) ◽  
pp. 611-615 ◽  
Author(s):  
Branka Koprivica ◽  
Teodora Beljic-Zivkovic ◽  
Tatjana Ille

Introduction. Insulin resistance is a well-known leading factor in the development of metabolic syndrome. The aim of this study was to evaluate metabolic effects of metformin added to sulfonylurea in unsuccessfully treated type 2 diabetic patients with metabolic syndrome. Material and methods. A group of thirty subjects, with type 2 diabetes, secondary sulfonylurea failure and metabolic syndrome were administered the combined therapy of sulfonylurea plus metformin for six months. Metformin 2000 mg/d was added to previously used sulfonylurea agent in maximum daily dose. Antihypertensive and hypolipemic therapy was not changed. The following parameters were assessed at the beginning and after six months of therapy: glycemic control, body mass index, waist circumference, blood pressure, triglycerides, total cholesterol and its fractions, homeostatic models for evaluation of insulin resistance and secretion (HOMA R, HOMA B) and C- peptide. Results. Glycemic control was significantly improved after six months of the combined therapy: (fasting 7.89 vs. 10.61 mmol/l. p<0.01; postprandial 11.12 vs. 12.61 mmol/l. p<0.01, p<0.01; glycosylated hemoglobin 6.81 vs. 8.83%. p<0.01). the body mass index and waist circumference were significantly lower (26.7 vs. 27.8 kg/m2, p<0.01 and 99.7 vs. 101.4 cm for men, p<0.01; 87.2 vs. 88.5 for women, p<0.01). Fasting plasma triglycerides decreased from 3.37 to 2.45 mmol/l (p<0.001) and HOMA R from 7.04 to 5.23 (p<0.001). No treatment effects were observed on blood pressure, cholesterol, and residual insulin secretion. Conclusion. Administration of metformin in type 2 diabetes with metabolic syndrome decreased cardiovascular risk factors by reducing glycemia, triglycerides, BMI, central obesity and insulin resistance.


Medicine ◽  
2017 ◽  
Vol 96 (39) ◽  
pp. e8126 ◽  
Author(s):  
Yiu-Hua Cheng ◽  
Yu-Chung Tsao ◽  
I-Shiang Tzeng ◽  
Hai-Hua Chuang ◽  
Wen-Cheng Li ◽  
...  

2003 ◽  
Vol 149 (4) ◽  
pp. 331-335 ◽  
Author(s):  
JV Silha ◽  
M Krsek ◽  
JV Skrha ◽  
P Sucharda ◽  
BL Nyomba ◽  
...  

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. METHODS: We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. RESULTS: Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. DISCUSSION: In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.


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