scholarly journals Enhanced cortisol production rates, free cortisol, and 11β-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss

2009 ◽  
Vol 296 (2) ◽  
pp. E351-E357 ◽  
Author(s):  
Jonathan Q. Purnell ◽  
Steven E. Kahn ◽  
Mary H. Samuels ◽  
David Brandon ◽  
D. Lynn Loriaux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Visceral Fat ◽  
Abdominal Fat ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Production Rates ◽  
Free Cortisol

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.

Concentrations, metabolic clearance rates, production rates and plasma binding of cortisol in Antarctic phocid seals

1993 ◽  
Vol 129 (4) ◽  
pp. 356-359 ◽  
Author(s):  
Graham C Liggins ◽  
John T France ◽  
Robert C Schneider ◽  
Bruce S Knox ◽  
Warren M Zapol
Keyword(s):  
Binding Capacity ◽  
Plasma Concentrations ◽  
Human Values ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Production Rates ◽  
High Production Rate ◽  
Free Cortisol ◽  
Phocid Seals ◽  
Cortisol Levels

We have reported previously that plasma of the Weddell seal, a member of the phocid family, contains a very high concentration of cortisol. The present study was undertaken to determine whether high cortisol levels were common to seals in the Antarctic environment, or to other phocidae, and to determine the mechanism of the hypercortisolaemia. High levels of cortisol (0.82–2.38 μmol/l) were found in 4 phocidae (Weddell, crabeater, leopard and Southern elephant seals), whereas levels in a member of the otariid family (Antarctic fur seal) were similar to human values. Metabolic clearance rates (MCR) and production rates (PR) of cortisol were determined in the field in Weddell (N = 1), crabeater (N= 3) and leopard (N= 3) seals following bolus injections of [3H] cortisol. The MCR and PR did not differ between the three phocids, but whereas the MCR of 410–590 1/day was twice that of human values, the PR of 460–1180 μmol·m−2·d−1 was up to 40-fold greater. The binding capacity of corticosteroid-binding globulin (CBG) was equal to or greater than the plasma concentrations of cortisol, resulting in relatively low concentrations of free cortisol. We conclude that hypercortisolaemia is maintained in phocid seals mainly by a high production rate—the highest (corrected for surface area) reported in any species. The relatively low cortisol levels in otariid seals studied in the same environment suggest that the high PR in phocidae is unrelated to the harsh climatic conditions, but may be part of their adaptation for diving to extreme depths. The phocid seals and New World primates have similarly high levels of cortisol and a high PR but CBG in the primates has low binding capacity and affinity and cortisol is mainly free.

scholarly journals The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2883 ◽  
Author(s):  
Juyeon Ko ◽  
Loren Skudder-Hill ◽  
Jaelim Cho ◽  
Sakina H. Bharmal ◽  
Maxim S. Petrov
Keyword(s):  
Insulin Resistance ◽  
Acute Pancreatitis ◽  
Insulin Sensitivity ◽  
Visceral Fat ◽  
Abdominal Fat ◽  
Model Assessment ◽  
Healthy Controls ◽  
Tyg Index ◽  
Pancreatic Fat ◽  
Matsuda Index

Both type 2 prediabetes/diabetes (T2DM) and new-onset prediabetes/diabetes after acute pancreatitis (NODAP) are characterized by impaired tissue sensitivity to insulin action. Although the outcomes of NODAP and T2DM are different, it is unknown whether drivers of insulin resistance are different in the two types of diabetes. This study aimed to investigate the associations between abdominal fat phenotypes and indices of insulin sensitivity in non-obese individuals with NODAP, T2DM, and healthy controls. Indices of insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA-IS), Raynaud index, triglyceride and glucose (TyG) index, Matsuda index) were calculated in fasting and postprandial states. Fat phenotypes (intra-pancreatic fat, intra-hepatic fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using magnetic resonance imaging and spectroscopy. Linear regression and relative importance analyses were conducted. Age, sex, and glycated hemoglobin A1c were adjusted for. A total of 78 non-obese individuals (26 NODAP, 20 T2DM, and 32 healthy controls) were included. Intra-pancreatic fat was significantly associated with all the indices of insulin sensitivity in the NODAP group, consistently in both the unadjusted and adjusted models. Intra-pancreatic fat was not significantly associated with any index of insulin sensitivity in the T2DM and healthy controls groups. The variance in HOMA-IS was explained the most by intra-pancreatic fat (R2 = 29%) in the NODAP group and by visceral fat (R2 = 21%) in the T2DM group. The variance in the Raynaud index was explained the most by intra-pancreatic fat (R2 = 18%) in the NODAP group and by visceral fat (R2 = 15%) in the T2DM group. The variance in the TyG index was explained the most by visceral fat in both the NODAP group (R2 = 49%) and in the T2DM group (R2 = 25%). The variance in the Matsuda index was explained the most by intra-pancreatic fat (R2 = 48%) in the NODAP group and by visceral fat (R2 = 38%) in the T2DM group. The differing association between intra-pancreatic fat and insulin resistance can be used to differentiate NODAP from T2DM. Insulin resistance in NODAP appears to be predominantly driven by increased intra-pancreatic fat deposition.

scholarly journals Expression of macrophage genes within skeletal muscle correlates inversely with adiposity and insulin resistance in humans

2018 ◽  
Vol 43 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Dongmei Liu ◽  
Flor Elisa Morales ◽  
Heidi. B. IglayReger ◽  
Mary K. Treutelaar ◽  
Amy E. Rothberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Muscle Tissue ◽  
Skeletal Muscle Tissue ◽  
Obese Patients ◽  
Weight Loss Intervention

Local inflammation in obese adipose tissue has been shown to contribute to insulin resistance; however, the role of macrophage infiltration within skeletal muscle is still debatable. This study aimed to evaluate the association of skeletal muscle macrophage gene expression with adiposity levels and insulin sensitivity in obese patients. Twenty-two nondiabetic obese patients and 23 healthy lean controls were included. Obese patients underwent a 3-month weight loss intervention. Macrophage gene expression in skeletal muscle (quantitative real-time polymerase chain reaction), body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (homeostatic model assessment (HOMA) and oral glucose tolerance test) were compared between groups and their associations were analyzed. To validate skeletal muscle findings, we repeated the analyses with macrophage gene expression in adipose tissue. Expression levels of macrophage genes (CD68, CD11b, CD206, CD16, CD40, and CD163) were lower in skeletal muscle tissue of obese versus lean participants. Macrophage gene expression was also found to be inversely associated with adiposity, fasting insulin, and HOMA (r = −0.4 ∼ −0.6, p < 0.05), as well as positively associated with insulin sensitivity (r = 0.4 ∼ 0.8, p < 0.05). On the other hand, adipose tissue macrophage gene expression showed higher levels in obese versus lean participants, presenting a positive association with adiposity levels. Macrophage gene expression, in both skeletal and adipose tissue samples, was only minimally affected by the weight loss intervention. In contrast with the established positive relationship between adiposity and macrophage gene expression, an unexpected inverse correlation between these 2 variables was observed in skeletal muscle tissue. Additionally, muscle macrophage gene expression was inversely correlated with insulin resistance.

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Pigment Epithelium ◽  
Pigment Epithelium Derived Factor ◽  
Human Preadipocytes

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 &lt; 0.0001), waist-to-hip ratio (r = 0.380; P &lt; 0.0001), HbA1c, and fasting triglycerides and negatively with insulin sensitivity (r = −0.320; P &lt; 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 &lt; 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.

Abstract P250: Insulin Resistance During Pregnancy is Inversely Associated With Gynoid Fat Distribution Postpartum

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Katherine H Ingram ◽  
Roxanna Lopez
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Gestational Weight Gain ◽  
Body Fat ◽  
Visceral Fat ◽  
Post Partum ◽  
Lower Body ◽  
Negatively Associated ◽  
Gestational Weight

An association between abdominal adiposity and insulin resistance is well-established. Recent research indicates that subcutaneous fat accumulation in the lower body may be associated with higher levels of insulin sensitivity. Hypothesis: This pilot study tested the hypothesis that the distribution of body fat in the lower body after pregnancy is negatively associated with gestational insulin resistance. Methods: In 32 nulliparous pregnant women (age 27±4.5, BMI 29.5±7.9, 69% non-hispanic white), the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed from fasting glucose and insulin at 24-28 weeks gestation. Body composition was assessed at mid-gestation (18-20 weeks) and at four weeks post-partum. Total body fat was estimated via bioelectrical impedance (InBody 720) and skinfold thicknesses were measured at seven sites. Dual-energy xray absorptiometry (DXA) measures of regional fat (gynoid, visceral, and leg) were obtained post-partum only. Gestational weight gain was monitored by medical records. Partial correlation analyses were controlled for age and race and then analyses were repeated controlling for baseline (mid-gestation) body fat percent. HOMA-IR was log-transformed for normality. Results: HOMA-IR was associated with post-partum body fat ( r =0.45, p < .05) and adiposity in the trunk region ( r =0.58, 0.57 and 0.52 for DXA visceral fat, suprailiac skinfold, and abdominal skinfold, respectively, p < .01), but not with gestational weight gain ( r =.07, p = ns), DXA gynoid region ( r = 0.26, p = ns), or any other leg measure. When analyses were further controlled for baseline body fat, post-partum measures of lower-body adiposity were strongly and negatively correlated with HOMA-IR ( r = -0.66, -0.48, and -0.48 for thigh skinfold, DXA gynoid, and DXA leg, respectively, p < .05 for all). Neither DXA visceral fat ( r = .23; p = ns) nor any other post-partum fat measures were associated with HOMA-IR when controlling for baseline body fat. Conclusions: Gestational insulin resistance was negatively associated with post-partum thigh fat accumulation, independent of overall body fat. These data indicate that insulin sensitivity may be associated with the ability to store fat in the lower body and should warrant further study of subcutaneous leg fat as a metabolically “healthy” storage depot.

scholarly journals Diosgenin and Its Fenugreek Based Biological Matrix Affect Insulin Resistance and Anabolic Hormones in a Rat Based Insulin Resistance Model

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Rita Kiss ◽  
Georgina Pesti-Asbóth ◽  
Mária Magdolna Szarvas ◽  
László Stündl ◽  
Zoltán Cziáky ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Treated Group ◽  
Severe Side Effect ◽  
Sensitivity Index ◽  
Metabolic Clearance ◽  
Anabolic Hormones ◽  
Fenugreek Seeds ◽  
Fenugreek Seed ◽  
Resistance Model

Fenugreek is known since ancient times as a traditional herbal medicine of its multiple beneficial effects. Fenugreek’s most studied and employed effect is its hypoglycemic property, but it can also be useful for the treatment of certain thyroid disorders or for the treatment of anorexia. The regulation of glucose homeostasis is a complex mechanism, dependent on the interaction of different types of hormones and neurotransmitters or other compounds. For the study of how diosgenin and fenugreek seeds modify insulin sensitivity, we used a rat insulin resistance model induced by high-fat diet. Diosgenin in three different doses (1mg/bwkg, 10mg/bwkg, and 50 mg/bwkg, respectively) and fenugreek seed (0.2 g/bwkg) were administered orally for 6 weeks. Insulin sensitivity was determined by hyperinsulinemic euglycemic glucose clamp method. Our research group found that although glucose infusion rate was not significantly modified in either group, the increased insulin sensitivity index and high metabolic clearance rate of insulin found in the 1 mg/kg diosgenin and the fenugreek seed treated group suggested an improved peripheral insulin sensitivity. Results from the 10 mg/kg diosgenin group, however, suggest a marked insulin resistance. Fenugreek seed therapy results on the investigated anabolic hormones support the theory that, besides insulin and gastrointestinal peptides, the hypothalamic-hypopituitary axis regulated hormones synchronized action with IGF-1 also play an important role in the maintaining of normal glucose levels. Both diosgenin and fenugreek seeds are capable of interacting with substrates of the above-mentioned regulatory mechanisms, inducing serious hormonal disorders. Moreover, fenugreek seeds showed the ability to reduce the thyroid hormone levels at the periphery and to modify the T4/T3 ratio. It means that in healthy people this effect could be considered a severe side effect; however, in hypothyroidism this effect represents a possibility of alternative natural therapy.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

scholarly journals The Relationship between Circulating Acetate and Human Insulin Resistance before and after Weight Loss in the DiOGenes Study

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 339
Author(s):  
Manuel A. González Hernández ◽  
Emanuel E. Canfora ◽  
Kenneth Pasmans ◽  
A. Astrup ◽  
W. H. M. Saris ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Positive Association ◽  
Fat Free Mass ◽  
Model Assessment ◽  
Random Factor ◽  
Before And After ◽  
Homeostatic Model Assessment ◽  
Matsuda Index

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index >27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (stdβ 0.130, p = 0.033) in women, but not in men (stdβ −0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats

2005 ◽  
Vol 289 (2) ◽  
pp. R486-R494 ◽  
Author(s):  
Andrea S. Rossi ◽  
Yolanda B. Lombardo ◽  
Jean-Marc Lacorte ◽  
Adriana G. Chicco ◽  
Christine Rouault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fish Oil ◽  
Essential Role ◽  
Control Diet ◽  
Insulin Resistant ◽  
Dietary Fish ◽  
Plasma Leptin

Insulin resistance and adiposity induced by a long-term sucrose-rich diet (SRD) in rats could be reversed by fish oil (FO). Regulation of plasma leptin and adiponectin levels, as well as their gene expression, by FO might be implicated in these findings. This study was designed to evaluate the long-term regulation of leptin and adiponectin by dietary FO in a dietary model of insulin resistance induced by long-term SRD in rats and to determine their impact on adiposity and insulin sensitivity. Rats were randomized to consume a control diet (CD; n = 25) or an SRD ( n = 50) for 7 mo. Subsequently, the SRD-fed rats were randomized to consume SRD+FO or to continue on SRD for an additional 2 mo. Long-term SRD induced overweight and decreased both plasma leptin and adiponectin levels without change in gene expression. Dyslipidemia, adiposity, and insulin resistance accompanied these modifications. Shifting the source of fat to FO for 2 mo increased plasma levels of both adipokines, reversed insulin resistance and dyslipidemia, and improved adiposity. These results were not associated with modifications in gene expression. These results suggest that increasing both adipokines by dietary FO might play an essential role in the normalization of insulin resistance and adiposity in dietary-induced, insulin-resistant models.

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