scholarly journals Circulating Pigment Epithelium-Derived Factor Levels Are Associated with Insulin Resistance and Decrease after Weight Loss

2010 ◽  
Vol 95 (10) ◽  
pp. 4720-4728 ◽  
Author(s):  
Mònica Sabater ◽  
Jose M. Moreno-Navarrete ◽  
Francisco José Ortega ◽  
Gerard Pardo ◽  
Javier Salvador ◽  
...  

Objective: We aimed to study circulating pigment epithelium-derived factor (PEDF) in vivo in association with insulin resistance and in vitro in human adipocytes. Methods: Circulating PEDF (ELISA) and metabolic profile were assessed in 125 Caucasian men. PEDF levels were also assessed in an independent cohort of subjects (n = 33) to study the effects of changing insulin action. PEDF gene expression and secretion were measured during differentiation of human preadipocytes. Results: In all subjects, PEDF was positively associated with body mass index (r = 0.326; P < 0.0001), waist-to-hip ratio (r = 0.380; P < 0.0001), HbA1c, and fasting triglycerides and negatively with insulin sensitivity (r = −0.320; P < 0.0001). PEDF levels were significantly increased in subjects with altered glucose tolerance and type 2 diabetes. Of the inflammatory markers measured, PEDF levels were positively associated with serum soluble TNF-α receptor 1 and IL-10 in obese subjects. Interestingly, weight loss led to significantly decreased PEDF concentration from 34.8 ± 19.3 to 22.5 ± 14.2 μg/ml (P < 0.0001). Multiple linear regression analyses revealed that insulin sensitivity contributed independently to explain 14% of the variance in PEDF levels after controlling for the effects of body mass index, age, and log fasting triglycerides. Differences in PEDF observed after weight loss were related to changes in obesity, insulin resistance, and blood pressure measures. PEDF gene expression and secretion increased during differentiation of human preadipocytes. Conclusion: Circulating PEDF is associated with insulin sensitivity. The findings show, for the first time in humans, that PEDF concentrations decrease significantly after weight loss in association with blood pressure. PEDF seems to be involved in human adipocyte biology.

1998 ◽  
Vol 83 (12) ◽  
pp. 4284-4288
Author(s):  
Robert A. Phillips ◽  
Lawrence R. Krakoff ◽  
Andrea Dunaif ◽  
Diane T. Finegood ◽  
Richard Gorlin ◽  
...  

Because left ventricular (LV) mass (LVM) is a powerful predictor of future cardiovascular events, it is important to identify hemodynamic and nonhemodynamic factors that increase LVM. We studied the separate contribution to LVM of daily arterial blood pressure (BP) and insulin resistance in a consecutive series of 29 (mean ± sd age, 43 ± 13 yr) nonobese (body mass index, 24 ± 1.8 kg/m2), nondiabetic, glucose-tolerant subjects with untreated borderline or mild hypertension. The insulin sensitivity index (SI) was quantitatively determined from the frequently sampled iv glucose tolerance test. BP was characterized by ambulatory 24-h BP monitoring, and LVM index (LVMI) was determined by two-dimensional directed M-mode echocardiography. LVMI was directly related to 24-h mean BP (r = 0.47; P = 0.01). LMVI was also significantly related to SI (r = −0.43; P = 0.02). In this nonobese group, neither LVMI nor SI was related to body mass index or age. After adjustment for the influence of BP on LVMI, a significant relation remained between LVMI and SI (P < 0.05). We conclude that in nonobese subjects with high normal BP, insulin sensitivity is related to LVM independently of BP and may be an important modulator of LV growth. In addition to a reduction of arterial BP, optimal prevention of LV hypertrophy in hypertensives may require improved insulin sensitivity.


2012 ◽  
Vol 97 (11) ◽  
pp. E2114-E2118 ◽  
Author(s):  
Kyle L. Sunderland ◽  
Jeanie B. Tryggestad ◽  
Joshua J. Wang ◽  
April M. Teague ◽  
Lauren V. Pratt ◽  
...  

Context: Pigment epithelium-derived factor (PEDF) was recently implicated as a metabolic regulatory protein because plasma concentration was increased in obese or insulin resistant adults. To our knowledge, circulating PEDF values in children have not been reported. Because PEDF is a predictor of metabolic health in adults, it may have a similar impact on metabolic profiles in children. Objective: The objective of the study was to determine whether PEDF in normal-weight (NW) and overweight/obese (OW) children and young adults varies with age, sex, or body composition or is associated with clinical markers of metabolic disease. Setting: Volunteers were tested at the University of Oklahoma Health Sciences Center. Participants: Ninety-one NW (8–30 yr old) and 105 OW (8–35 yr old) males and females participated in the study. Main Outcome Measures: Body composition, blood pressure, arterial compliance, fasting plasma PEDF, glucose, insulin, (used for homeostasis model assessment of insulin resistance), triglycerides, cholesterol (total, low density lipoprotein, and high density lipoprotein), and C-reactive protein. Results: PEDF was 60% higher in the OW vs. NW participants but did not differ between males and females. PEDF was positively correlated with body mass, body mass index, fat and lean mass, fasting insulin, and homeostasis model assessment of insulin resistance in both the NW and OW groups. Multiple regression models revealed that fat and lean mass were significant predictors of circulating PEDF levels independent of age, sex, and body mass index category. Conclusions: Plasma PEDF is elevated in OW youth and is positively associated with insulin resistance. These findings suggest that PEDF may play a role in the development of cardiometabolic dysfunction in youth.


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.


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.


2008 ◽  
Vol 93 (6) ◽  
pp. 2287-2293 ◽  
Author(s):  
Thomas Reinehr ◽  
Birgit Stoffel-Wagner ◽  
Christian L. Roth

Abstract Context: There are limited and controversial data concerning the relationships between retinol-binding protein 4 (RBP4), weight status, and insulin resistance in obese humans and especially in children. Objective: Our objective was to study the longitudinal relationships among RBP4, insulin resistance and weight status in obese children. Design, Setting, and Patients: We conducted a 1-yr longitudinal follow-up study in a primary-care setting with 43 obese children (median age 10.8 yr) and 19 lean children of same the age and gender. Intervention: Our outpatient 1-yr intervention program was based on exercise, behavior, and nutrition therapy. Main Outcomes Measures: Changes of weight status (body mass index sd score), RBP4, molar RBP4/serum retinol (SR) ratio, insulin resistance index homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). Results: Obese children had significantly (P &lt; 0.01) higher RBP4 concentrations and a higher RBP4/SR ratio compared with lean children. In multiple linear regression analyses adjusted to age, gender, and pubertal stage, RBP4 was significantly correlated to insulin and body mass index. Pubertal children demonstrated significantly decreased QUICKI and significantly increased HOMA index, insulin, and RBP4 concentrations compared with prepubertal children. Changes of RBP4 correlated significantly to changes of insulin (r = 0.29), HOMA index (r = 0.29), QUICKI (r = 0.22), and weight status (r = 0.31). Substantial weight loss in 25 children led to a significant (P &lt; 0.001) decrease of RBP4, RBP4/SR, blood pressure, triglycerides, insulin, and HOMA index and an increase in QUICKI in contrast to the 18 children without substantial weight loss. Conclusion: RBP4 levels were related to weight status and insulin resistance in both cross-sectional and longitudinal analyses, suggesting a relationship between RBP4, obesity, and insulin resistance in children.


2009 ◽  
Vol 296 (2) ◽  
pp. E351-E357 ◽  
Author(s):  
Jonathan Q. Purnell ◽  
Steven E. Kahn ◽  
Mary H. Samuels ◽  
David Brandon ◽  
D. Lynn Loriaux ◽  
...  

Controversy exists as to whether endogenous cortisol production is associated with visceral obesity and insulin resistance in humans. We therefore quantified cortisol production and clearance rates, abdominal fat depots, insulin sensitivity, and adipocyte gene expression in a cohort of 24 men. To test whether the relationships found are a consequence rather than a cause of obesity, eight men from this larger group were studied before and after weight loss. Daily cortisol production rates (CPR), free cortisol levels (FC), and metabolic clearance rates (MCR) were measured by stable isotope methodology and 24-h sampling; intra-abdominal fat (IAF) and subcutaneous fat (SQF) by computed tomography; insulin sensitivity (SI) by frequently sampled intravenous glucose tolerance test; and adipocyte 11β-hydroxysteroid dehydrogenase-1 (11β-HSD-1) gene expression by quantitative RT-PCR from subcutaneous biopsies. Increased CPR and FC correlated with increased IAF, but not SQF, and with decreased SI. Increased 11β-HSD-1 gene expression correlated with both IAF and SQF and with decreased SI. With weight loss, CPR, FC, and MCR did not change compared with baseline; however, with greater loss in body fat than lean mass during weight loss, both CPR and FC increased proportionally to final fat mass and IAF and 11β-HSD-1 decreased compared with baseline. These data support a model in which increased hypothalamic-pituitary-adrenal activity in men promotes selective visceral fat accumulation and insulin resistance and may promote weight regain after diet-induced weight loss, whereas 11β-HSD-1 gene expression in SQF is a consequence rather than cause of adiposity.


2005 ◽  
Vol 90 (3) ◽  
pp. 1360-1365 ◽  
Author(s):  
C. Ortega-González ◽  
S. Luna ◽  
L. Hernández ◽  
G. Crespo ◽  
P. Aguayo ◽  
...  

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P ≤ 0.05) after pioglitazone treatment but not after metformin treatment. Fasting serum insulin concentration (P &lt; 0.001 for both drugs) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone (P &lt; 0.002) or metformin (P &lt; 0.05) treatment. IR (homeostasis model of assessment-IR index) decreased and insulin sensitivity (elevation of the quantitative insulin sensitivity check index and the fasting glucose to insulin ratio) increased (P ≤ 0.008) after treatment with either drug. Hirsutism (P &lt; 0.05) and serum concentrations of free testosterone (P &lt; 0.02) and androstenedione (P &lt; 0.01) declined to a similar extent after treatment with the drugs. Treatment with pioglitazone or metformin was associated with the occurrence of pregnancy (n = 5 and n = 3, respectively). These results suggest that pioglitazone is as effective as metformin in improving insulin sensitivity and hyperandrogenism, despite an increase in body weight, body mass index, and the waist to hip ratio associated with pioglitazone.


2007 ◽  
Vol 135 (7-8) ◽  
pp. 440-446 ◽  
Author(s):  
Biljana Beleslin ◽  
Jasmina Ciric ◽  
Milos Zarkovic ◽  
Zorana Penezic ◽  
Svetlana Vujovic ◽  
...  

Introduction Obesity is often accompanied by a number of complications including diabetes mellitus and cardiovascular diseases. Elevated blood pressure and lipids, as well as deterioration of glucoregulation are attributed, as the most significant factors, to development of diabetes mellitus and cardiovascular complications in obese patients. Objective The aim of our study was to evaluate the effects of a fasting diet on blood pressure, lipid profile and glucoregulatory parameters. Method We included 110 patients (33 male and 77 female; mean age 35?1 years, body weight 131.7?2.6 kg, body mass index 45.4?0.8 kg/m2) who were hospitalized for three weeks for the treatment of extreme obesity with the fasting diet. At the beginning, during, and at the end of this period, we evaluated changes in blood pressure, lipid profile, as well as parameters of glucoregulation including glycaemia, insulinaemia, and insulin sensitivity by HOMA. Oral glucose tolerance test (OGTT) was performed in all patients at the beginning and at the end of the fasting diet. Results During the fasting diet, the body weight decreased from 131.7?2.6 kg to 117.7?2.4 kg (p<0.001), the body mass index decreased from 45.4?0.8 kg/m2 to 40.8?0.8 kg/m2 (p<0.001), and both systolic and diastolic blood pressure significantly declined (143?2 vs. 132?2 mm Hg, p<0.001; 92?2 vs. 85?2 mm Hg, p<0.001). In addition, the fasting diet produced a significant decrease in total cholesterol, LDL cholesterol, triglycerides, as well as basal glycaemia and insulinaemia (p<0.001) Before the fasting diet, OGTT was normal in 76% of patients, whereas 21% of patients showed glucose intolerance, and 4% of patients diabetes mellitus. After the fasting diet, OGTT was normal in 88% of patients, whereas 12% of patients still had signs of glucose intolerance (p<0.05). In addition, insulin resistance significantly (p<0.05) increased from 54?6% to 89?13% after the fasting diet. Conclusion The three-week fasting diet in extremely obese patients produced a significant decrease and normalization of blood pressure, decrease in lipids, and improvement in glucoregulation including the increase in insulin sensitivity.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2174
Author(s):  
Guilherme da Silva Ferreira ◽  
Ana Paula Garcia Bochi ◽  
Paula Ramos Pinto ◽  
Vanessa Del Bianco ◽  
Letícia Gomes Rodrigues ◽  
...  

Background: A low-sodium (LS) diet reduces blood pressure, contributing to the prevention of cardiovascular diseases. However, intense dietary sodium restriction impairs insulin sensitivity and worsens lipid profile. Considering the benefits of aerobic exercise training (AET), the effect of LS diet and AET in hepatic lipid content and gene expression was investigated in LDL receptor knockout (LDLr-KO) mice. Methods: Twelve-week-old male LDLr-KO mice fed a normal sodium (NS) or LS diet were kept sedentary (S) or trained (T) for 90 days. Body mass, plasma lipids, insulin tolerance testing, hepatic triglyceride (TG) content, gene expression, and citrate synthase (CS) activity were determined. Results were compared by 2-way ANOVA and Tukey’s post-test. Results: Compared to NS, LS increased body mass and plasma TG, and impaired insulin sensitivity, which was prevented by AET. The LS-S group, but not the LS-T group, presented greater hepatic TG than the NS-S group. The LS diet increased the expression of genes related to insulin resistance (ApocIII, G6pc, Pck1) and reduced those involved in oxidative capacity (Prkaa1, Prkaa2, Ppara, Lipe) and lipoprotein assembly (Mttp). Conclusion: AET prevented the LS-diet-induced TG accumulation in the liver by improving insulin sensitivity and the expression of insulin-regulated genes and oxidative capacity.


2007 ◽  
Vol 92 (5) ◽  
pp. 1843-1847 ◽  
Author(s):  
Dalit Modan-Moses ◽  
Daniel Stein ◽  
Clara Pariente ◽  
Amit Yaroslavsky ◽  
Anka Ram ◽  
...  

Abstract Context: Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting. Objective: Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters. Design, Setting, and Participants: We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight). Main Outcome Measures: Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured. Results: At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T4 or cortisol levels. Conclusions: Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.


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