Insulin Resistance In Obese Adults Research Articles

Comparison of Predictive Value of Obesity and Lipid Related Variables for Metabolic Syndrome and Insulin Resistance in Obese Adults

Comparison of Predictive Value of Obesity and Lipid Related Variables for Metabolic Syndrome and Insulin Resistance in Obese Adults

Perinatal overnutrition exacerbates adipose tissue inflammation caused by high-fat feeding in C57BL/6J mice.

Obesity causes white adipose tissue (WAT) inflammation and insulin resistance in some, but not all individuals. Here, we used a mouse model of early postnatal overfeeding to determine the role of neonatal nutrition in lifelong WAT inflammation and metabolic dysfunction. C57BL/6J mice were reared in small litters of 3 (SL) or normal litters of 7 pups (NL) and fed either regular chow or a 60% high fat diet (HFD) from 5 to 17 weeks. At weaning, SL mice did not develop WAT inflammation despite increased fat mass, although there was an up-regulation of WAT Arg1 and Tlr4 expression. On HFD, adult SL mice had greater inguinal fat mass compared to NL mice, however both groups showed similar increases in visceral fat depots and adipocyte hypertrophy. Despite the similar levels of visceral adiposity, SL-HFD mice displayed greater impairments in glucose homeostasis and more pronounced hepatic steatosis compared to NL-HFD mice. In addition, WAT from SL mice fed a HFD displayed greater crown-like structure formation, increased M1 macrophages, and higher cytokine gene expression. Together, these data suggest that early postnatal overnutrition may be a critical determinant of fatty liver and insulin resistance in obese adults by programming the inflammatory capacity of adipose tissue.

Changes of leptin, but not ghrelin or n‐6/n‐3 polyunsaturates, correlate with improvements in insulin resistance in obese adults following weight loss

Obesity may lead to insulin resistance, type 2 diabetes, and coronary heart diseases. Leptin, ghrelin, and polyunsaturates play different roles in insulin sensitivity. We assessed the impact of weight loss on insulin resistance, serum leptin/ghrelin, and erythrocyte n-6/n-3 polyunsaturate profile. The intervention group constituted twenty-eight obese adults participating in a dietitian-led weight loss program, and the control lean individuals (n=14) were recruited from the community. The intervention subjects had a mean weight loss of 5.7±3.9 kg followed by a 19.7% and 22.5% reduction in HOMA-IR and leptin, and an 11.75% increase in ghrelin (all p<0.05). Erythrocyte n-6 and n-3 polyunsaturates increased by 3.0% and 17.2% (all p<0.05). Leptin changes, but not ghrelin or n-6/n-3 polyunsaturates, significantly differed (p<0.05) in those with improved insulin resistance after weight loss (changes of HOMA-IR<0) than those with no improvement (changes of HOMA-IR≥). After adjusting for weight change, increased leptin independently correlated with increased risk of no improvement in HOMA-IR (OR=1.80, p=0.04). In conclusion, participants following weight loss had improvements in insulin resistance and several metabolic parameters. Insulin resistance improvement may have been partially mediated by leptin.

Effect of dietary restriction and n‐3PUFA supplementation on insulin resistance in obese adults

The type and amount of dietary fat, and in particular n‐3 PUFA, may influence insulin action. The aim of this study was to examine the effects on HOMA indices from increased n‐3 PUFA intakes at 3 and 6 months in a registered 12 month weight loss trial [ACTRN12608000425392]. The blinded RCT with 30 males and 88 females (aged 45+9.95yr; BMI 31.34+3.49kgm−2) compared a control diet (2MJ deficit, 30%fat + placebo) with two intervention groups (2MJ deficit, 30% fat emphasizing fish with placebo or supplement of 420mg EPA+ 210mg DHA). Differences between groups were assessed using repeated measures analysis of variance, where data was available at 0,3,6mo (n=73). A significant time effect was found for decreased HOMA‐R (inverse of %S) (P=0.001), with post hoc analysis showing a significant difference between 0–3mo (P=0.006) and 0–6mo (P=0.002). Values for the control group were higher than for the intervention groups but the effect was not significant at 3–6mo (P=1.000). No effect was seen for HOMA(%β) (N=72). Energy restriction appears to decrease insulin resistance in overweight adults in the first 3 mo, and there may be added benefits with food or supplemental n‐3 PUFA dietary enrichment.Source of research support: Australian National Health and Medical Research Council Project Grant #514631 Tapsell, Batterham, Charlton.

Variations of retinol binding protein 4 levels are not associated with changes in insulin resistance during puberty

Retinol binding protein 4 (RBP4) is an adipokine involved in the pathogenesis of insulin resistance in obese adults and children. Since insulin resistance occurs during puberty, independently of adiposity, a role for RBP4 in the onset of this phenomenon may be hypothesized. In order to verify our hypothesis, we studied 90 subjects (45 obese and 45 lean controls). A complete physical examination was assessed, the z-score body mass index (BMI) was calculated, fat mass was assessed by bioelectric impedance analysis, and pubertal stage was assessed according to Tanner. Serum insulin and serum RBP4 levels were assayed. Obese and lean children differed for z-score BMI, fat mass, homeostasis model assessment of insulin resistance (HOMA-IR) and RBP4 levels. z-score BMI and HOMA-IR showed a direct correlation with RBP4 in the total population. When the subjects were divided in lean and obese, this correlation was evident only in obese (r2: 0.2; p=0.009 and r2: 0.2; p=0.01), but not in lean subjects (r2: 0.09; p=0.1 and r2: 0.03; p=0.4). Both in obese and lean HOMA-IR values were higher in pubertal subjects than in pre-pubertal (p<0.001), while serum RBP4 levels were similar in pubertal and in pre-pubertal subjects (>0.1). We conclude that RBP4 is correlated with adiposity and insulin resistance in obese children, but it is not involved in the insulin resistance occurring during puberty.

Retinol to Retinol-Binding Protein (RBP) Is Low in Obese Adults due to Elevated apo-RBP

Elevated serum retinol-binding protein (RBP) concentration has been associated with obesity and insulin resistance, but accompanying retinol values have not been reported. Assessment of retinol is required to discriminate between apo-RBP, which may act as an adipokine, and holo-RBP, which transports vitamin A. The relations between serum RBP, retinol, retinyl esters, BMI, and measures of insulin resistance were determined in obese adults. Fasting blood (> or =8 h) was collected from obese men and women (n = 76) and blood chemistries were obtained. Retinol and retinyl esters were quantified by HPLC and RBP by ELISA. RBP and retinol were determined in age and sex-matched, nonobese individuals (n = 41) for comparison. Serum apo-RBP was two-fold higher in obese (0.90 +/- 0.62 microM) than nonobese subjects (0.44 +/- 0.56 microM) (P < 0.001). The retinol to RBP ratio (retinol:RBP) was significantly lower in obese (0.73 +/- 0.13) than nonobese subjects (0.90 +/- 0.22) (P < 0.001) and RBP was strongly associated with retinol in both groups (r = 0.71 and 0.90, respectively, P < 0.0001). In obese subjects, RBP was associated with insulin (r = 0.26, P < 0.05), homeostatic model assessment of insulin resistance (r = 0.29, P < 0.05), and quantitative insulin sensitivity check index (r = -0.27, P < 0.05). RBP was associated with BMI only when obese and nonobese subjects were combined (r = 0.25, P < 0.01). Elevated serum RBP, derived in part from apo-RBP, was more strongly associated with retinol than with BMI or measures of insulin resistance in obese adults. Investigations into the role of RBP in obesity and insulin resistance should include retinol to facilitate the measurement of apo-RBP and retinol:RBP. When evaluating the therapeutic potential of lowering serum RBP, consideration of the consequences of vitamin A metabolism is paramount.

Retinol-Binding Protein 4 and Lipocalin-2 in Childhood and Adolescent Obesity: When Children Are Not Just “Small Adults”

although there is much evidence regarding the physiologic and pathogenic roles of the newly described adipokines retinol-binding protein 4 (RBP4) and lipocalin-2 as potential promoters of insulin resistance in obese adults, relatively little information exists regarding their roles in obese children. we investigated the circulating concentrations of RBP4 and lipocalin-2 in 80 obese girls (ages 9- 15 years) and their relationships with high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin. We divided participants by their body mass index standard deviation scores (BMI SDSs) into 4 groups of 20 girls each: overweight [mean BMI SDS (SD), 1.8 (0.4)], obese [2.2 (0.4)], morbidly obese [3.6 (0.4)], and lean controls [-0.11 (0.4)]. We measured plasma-soluble RBP4, the RBP4-binding protein transthyretin, lipocalin-2, hs-CRP, leptin, and adiponectin and calculated the homeostatic assessment model (HOMA) index from fasting glucose and insulin concentrations. unexpectedly, plasma RBP4 and lipocalin-2 concentrations were correlated negatively with BMI SDS values (P = 0.005, and P < 0.03, respectively). These results were different from those of adults and were not correlated with the HOMA index. In contrast, hs-CRP and leptin concentrations were positively correlated with BMI SDS values (P < 0.0001, and P < 0.00001, respectively), as expected, whereas the adiponectin concentration was negatively correlated (P = 0.008). although the correlations of leptin, adiponectin, and hs-CRP concentrations with BMI in children are similar to those of adults, the correlations of RBP4 and lipocalin-2 with BMI in children are the inverse of those observed in adults. Thus, although systemic inflammation and mild insulin resistance are present in childhood obesity, RBP4 and lipocalin-2 concentrations are not increased in children as they are in obese adults with long-standing severe insulin resistance and type 2 diabetes.