Insulin Resistance In Obese Women Research Articles

Comparative Study of Insulin Sensitivity and Resistance and Their Correlation with Androgens in Lean and Obese Women with Polycystic Ovary Syndrome.

There is a lack of consensus on the optimal screening strategy for insulin resistance (IR), particularly in lean women with polycystic ovary syndrome (PCOS). Therefore, we conducted a cross-sectional study in 80 women with PCOS (28 lean/52 obese) and 80 age- and body mass index (BMI)-matched controls. Using a 5-point 75-g oral glucose tolerance test (OGTT) (0, 30, 60, 90, 120min), we examined glucose and insulin excursions, IR, insulin sensitivity, beta-cell function (ßF), and the effect of androgens on IR. Lean and obese women with PCOS had similar glucose but higher insulin (except fasting in lean women) and insulin AUC as compared to their respective controls (p < 0.05). Lean women with PCOS were equally insulin-resistant but more hyperinsulinemic than the obese controls (p < 0.05). Although ßF ([1st phase: 481.71 ± 263.53 vs. 430.56 ± 232.37], [2nd phase: 815.16 ± 447.12 vs. 752.66 ± 428.95]) was comparable in lean and obese women with PCOS, lean women had better insulin sensitivity (112.78 ± 66.26 vs. 75.49 ± 55.6) (p < 0.05). Dehydroepiandrosterone sulfate (DHEAS) and androstenedione decreased with increasing BMI in lean women, and this correlated with deteriorating insulin sensitivity and exaggerated hyperinsulinemia. In obese women with PCOS, sex hormone-binding globulin (SHBG) correlated negatively with BMI and hyperinsulinemia, and positively with insulin sensitivity. This data suggests that estimating only fasting insulin may miss IR in lean women with PCOS; hence, additional time points in OGTT will add value to screening for IR. DHEAS and androstenedione may have a beneficial effect on insulin sensitivity and may be used to screen IR in lean women, while SHBG can be used as a predictive marker for IR in obese women with PCOS.

Differences in DNA methylation of HAMP in blood cells predicts the development of type 2 diabetes

ObjectivesBetter disease management can be achieved with earlier detection through robust, sensitive, and easily accessible biomarkers. The aim of the current study was to identify novel epigenetic biomarkers determining the risk of type 2 diabetes (T2D). MethodsLivers of 10-week-old female New Zealand Obese (NZO) mice, slightly differing in their degree of hyperglycemia and liver fat content and thereby in their diabetes susceptibility were used for expression and methylation profiling. We screened for differences in hepatic expression and DNA methylation in diabetes-prone and -resistant mice, and verified a candidate (HAMP) in human livers and blood cells. Hamp expression was manipulated in primary hepatocytes and insulin-stimulated pAKT was detected. Luciferase reporter assays were conducted in a murine liver cell line to test the impact of DNA methylation on promoter activity. ResultsIn livers of NZO mice, the overlap of methylome and transcriptome analyses revealed a potential transcriptional dysregulation of 12 hepatokines. The strongest effect with a 52% decreased expression in livers of diabetes-prone mice was detected for the Hamp gene, mediated by elevated DNA methylation of two CpG sites located in the promoter. Hamp encodes the iron-regulatory hormone hepcidin, which had a lower abundance in the livers of mice prone to developing diabetes. Suppression of Hamp reduces the levels of pAKT in insulin-treated hepatocytes. In liver biopsies of obese insulin-resistant women, HAMP expression was significantly downregulated along with increased DNA methylation of a homologous CpG site. In blood cells of incident T2D cases from the prospective EPIC-Potsdam cohort, higher DNA methylation of two CpG sites was related to increased risk of incident diabetes. ConclusionsWe identified epigenetic changes in the HAMP gene which may be used as an early marker preceding T2D.

New therapeutic opportunities in improving the antenatal management of obese women

Research objectives: to assess the effectiveness of the developed treatment complex on the course of pregnancy and childbirth in obese women.Materials and methods. 135 pregnant women were examined depending on the degree of obesity and received treatment. The women were examined and treated in the Department of Pathology of Pregnancy and Childbirth, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine” during 2019–2021.The developed medical complex included: Miofolic 2 sachets/day 3 months before pregnancy and throughout the gestation period; in case of insufficiency or deficiency of vitamin D, this vitamin was prescribed in a dose of 4000 IU/day; magnesium citrate 250–300 mg/day during pregnancy; micronized progesterone vaginally 200–400 mg/day in the II phase of the menstrual cycle before conception and up to 34 weeks of gestation (if necessary); individual programs of prenatal psychological rehabilitation using psychophysical exercises were used depending on the psychosomatic disorders.Results. it was found that the number of pregnant women of older reproductive age is increasing. There was a decrease in pre-pregnancy weight (which was positively reflected in the subsequent course of pregnancy) at the 3 months before the onset of pregnancy in women with lifestyle modification (diet therapy, dosed physical activities) and who intake a developed treatment complex at the pre-gravid stage.A peculiarity of the somatic morbidity of pregnant women was the combination of various types of extragenital diseases. Significant differences were found between chronic diseases of the cardiovascular system and diseases of the gastrointestinal tract and liver compared to the control group. The course of pregnancy largely depended on the reproductive system status before fertilization – an increase in the frequency of infertility was noted with an increase in the woman’s body mass index.Pregnant women who received the developed treatment complex had fewer pregnancy complications, the frequency of which was not significantly different from the control group. At the same time, against the background of the treatment, their lipid profile and vitamin and mineral supply improved. All this had a positive effect on the pregnancy outcomes.Conclusions. Developed medical complex including myo-inositol, starting from the pre-gravid period and throughout pregnancy, helps to reduce insulin resistance in obese women, improve the lipid profile and normalize the leptin level, which has a positive effect on the course of pregnancy and childbirth and improves perinatal outcomes.

Roles of C-Peptide and Triglyceride as Effective Indices for Insulin Resistance Investigations in Iraqi Women with Polycystic Ovarian Syndrome

Objectives: To assess how much Insulin Resistance (IR) in both obese and non-obese PCOS women used as index of PCOS and find out a correlation between various methods used for evaluation of IR.Methods: A study included 120 participants (68 women have PCOS subdivide according to their BMI to 45 obese (BMI&gt;=30) and 23 non-obese (BMI&lt;30). The remaining 52 participants represent as apparently control group with normal weight and normal menstrual cycle. Patients with PCOS were selected from the Infertility Department, Gynecology and Obstetrics Teaching Hospital in Kerbala, Iraq between Nov., 2021 and June, 2022. Diagnosis of PCOS is based on 2 of 3 findings: oligo/anovulation, hyperandrogenism, polycystic ovaries in ultrasound (Rotterdam criteria). Patients were interviewed and examined for weight, height, waist and hip circumferences. Venous blood samples were collected and insulin resistance was assessed by different methods including homeostatic model assessment of insulin resistance (HOMA-IR), G/I ratio, QUICKI, McAuly, TyG index and C-peptide index.Results: The assessment of IR revealed that HOMA-IR, QUICKI, McAuley, TyG and CPI had significant difference in both PCOS groups compared with controls. G/I ratio was significantly higher in the controls than obese PCOS women. The prevalence of IR based on (HOMA-IR) was 80% in obese PCOS and 48% in non-obese PCOS women. In obese PCOS women HOMA-IR strongly and negatively correlates with G/I ratio (r= -0.81, P&lt;0.001), QUICKI (r= -0.89, P&lt;0.001), McAuley (r= -0.79, P&lt;0.001) and C-peptide (r= -0.56, P&lt;0.001). Whereas it was positively correlates with insulin (r=0.99, P&lt;0.001), C-peptide (r=0.71, P&lt;0.001) and TyG index (r=0.51, P&lt;0.001). In non-obese PCOS women, HOMA-IR strongly and negatively correlates with G/I ratio (r= -0.79, P&lt;0.001), QUICKI (r= -0.93, P&lt;0.001) and McAuley (r= -0.77, P&lt;0.001). Whereas it was positively correlates with insulin (r=0.99, P&lt;0.001), C-peptide (r=0.49, P&lt;0.05) and TyG index (r=0.47, P&lt;0.05).Conclusion: The observed results concluded that TyG is a valuable indicator to predict IR in obese women with PCOS, partly due to its analytical and financial ease-of-access in all clinical laboratories. The use of TyG index is recommended in the assessment of IR risk among Iraqi women with PCOS.

Comparison of triglyceride-glucose index and HOMA-IR as indicators of insulin resistance in obese women with subclinical hypothyroidism

Introduction and aim. Thyroid hormones play an important role in glucose metabolism as in many metabolic events. The aim of our study is to evaluate the relationship between subclinical hypothyroidism (SCH) and insulin resistance, especially in obese women. Material and methods. Newly diagnosed SCH patients with body mass index (BMI) ≥30 who applied to our outpatient clinic between March 2021 and October 2021, and euthyroid obese women who applied for routine control were included in the study. In this study, we used homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose (TyG) indexes, which are noninvasive, simple and useful methods for evaluating insulin sensitivity. Results. The study included 78 female patients between the ages of 19 and 64. A correlational analysis was performed between thyroid stimulating hormone (TSH) and HOMA-IR, TyG, and BMI. The results showed that TSH levels were positively correlated with HOMA-IR (R=0.297, p=0.008), TyG (R=0.316, p=0.005) and BMI (R=0.307, p=0.006). This relationship was stronger for TyG compared to the other variables. As another finding, BMI was positively correlated with HOMA-IR (R=0.359, p=0.001) and TyG (R=0.404, p&lt;0.001). This relationship was stronger for TyG than HOMA-IR. Conclusion. These results show that patients with SCH are at risk of developing diseases that accompany insulin resistance, such as metabolic syndrome and cardiovascular disorders. The most important finding of our study is that the TyG index gives more significant results than HOMA-IR, especially in obese women.

Prevalence of Vitamin D Deficiency and Its Association with Insulin Resistance in Obese Women with Normal Fasting Glucose.

Results A total of 264 obese and 133 normal BMI women (controls) of age range 20-50 years were selected. Obese women had significantly lower vitamin D compared to control women (P < 0.05). Among euglycemic (fasting glucose < 100 mg/dl) obese women (n = 221), 90 (40.7%) were vitamin D deficient. Serum PTH and calcium levels were negatively correlated, though nonsignificantly with vitamin D (r = −0.172, P = 0.090, and r = −0.051, P = 0.557, respectively). The mean age, BMI, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), fasting glucose, fasting insulin, PTH, and calcium were not significantly different in vitamin D-deficient as compared to nondeficient obese women. IR was detected in 109 (49.3%) obese women. Mean HOMA-IR in vitamin D-deficient women was significantly higher than that in the nondeficient obese women (3.03 ± 1.64 vs. 2.40 ± 1.02; P = 0.041), but the percentage of women with IR was comparable in both groups (51.1% vs. 45.8%; P = 0.745). Univariate analysis revealed that HOMA-IR was negatively correlated with vitamin D and positively with BMI and PTH. A multivariate regression analysis, stepwise method revealed that BMI and PTH were independent determinants of HOMA-IR instead of vitamin D. Conclusion More than 40% of obese women were vitamin D deficient. Among euglycemic obese women, 49% were insulin resistant. Prevalence of insulin resistance, though negatively correlated with vitamin D, could be better explained by BMI and PTH levels.

IFNγ-producing NK cells in adipose tissue are associated with hyperglycemia and insulin resistance in obese women.

Innate lymphoid cells (ILCs) play an important role in the maintenance of immune and metabolic homeostasis in adipose tissue (AT). The crosstalk between AT ILCs and adipocytes and other immune cells coordinates adipocyte differentiation, beiging, glucose metabolism and inflammation. Although the metabolic and homeostatic functions of mouse ILCs have been extensively investigated, little is known about human adipose ILCs and their roles in obesity and insulin resistance (IR). Here we characterized T and NK cell populations in omental AT (OAT) from women (n = 18) with morbid obesity and varying levels of IR and performed an integrated analysis of metabolic parameters and adipose tissue transcriptomics. In OAT, we found a distinct population of CD56-NKp46+EOMES+ NK cells characterized by expression of cytotoxic molecules, pro-inflammatory cytokines, and markers of cell activation. AT IFNγ+ NK cells, but not CD4, CD8 or γδ T cells, were positively associated with glucose levels, glycated hemoglobin (HbA1c) and IR. AT NK cells were linked to a pro-inflammatory gene expression profile in AT and developed an effector phenotype in response to IL-12 and IL-15. Moreover, integrated transcriptomic analysis revealed a potential implication of AT IFNγ+ NK cells in controlling adipose tissue inflammation, remodeling, and lipid metabolism. Our results suggest that a distinct IFNγ-producing NK cell subset is involved in metabolic homeostasis in visceral AT in humans with obesity and may be a potential target for therapy of IR.

Impact of Nutritional Intervention on Serum Level of Interferon Gamma and Insulin Resistance in Obese Women: Considerations during the COVID-19 Crisis

BACKGROUND: Obesity represents a major epidemic worldwide; it is accompanied by increased oxidative stress and reduction in immune efficacy.&#x0D; AIM: The objective was to assess the impact of a healthy balanced hypocaloric diet with two dietary supplements on obesity related metabolic disorders and interferon gamma production.&#x0D; SUBJECTS AND METHODS: Sixty obese women participated in the study that lasted for 8 weeks. They were divided into two groups, 30 subjects in each group, one group consumed a daily supplement in the form of cookies prepared mainly from corn flour, wheat germ and thyme, and the other consumed a blend composed mainly of barley flour, cocoa powder and ginger powder. All participants have followed a low caloric balanced regimen (1000-1200 KCal/day). Follow-up was performed with anthropometric measurements, dietary recall, and biochemical parameters.&#x0D; RESULTS: After intervention, the results showed a significant reduction in the anthropometric parameters, the obesity related metabolic disorders criteria with significant elevation in total antioxidant and interferon gamma. Positive significant correlations were detected between total antioxidant and interferon gamma and negative significant correlations were detected between interferon gamma with triglycerides, body mass index, percent body fat mass, and hip circumferences.&#x0D; CONCLUSION: All these issues have a very important role in decreasing the infection with covid-19.

Insulin Resistance in Obese Women: Does it Affect Fertility?

Objective: To know the correlation of insulin resistance with body mass index in obesity women infertility.Method: This research used a cross-sectional study design. This study was conducted on February 2017 until January 2019 at Obstetric and Gynecology Division of RSUP Dr. M. Djamil and Ibnu Sina Hospital in Padang. The population of the study were all patients were obese in women of reproductive age with infertility complaints with a total sample of 27 people. The sampling technique was consecutive sampling. Data analysis was done by univariate and bivariate using Pearson correlation test.Results: We found that less than half of the respondents experienced insulin resistance with HOMA-IR values &gt; 2,5 (22.2%) and more than half of respondents did not experience insulin resistance with HOMA-IR values &lt; 2,5 (77.8%). There was a correlation of insulin resistance with body mass index in obese female infertility (p&lt;0,05) with strong relationship strength. Conclusions: There was a correlation of insulin resistance with body mass index in obese female infertility.Keywords: infertility, insulin resistance, obesity&#x0D; &#x0D; Abstrak&#x0D; Tujuan: Mengetahui korelasi resistensi insulin dengan indeks massa tubuh pada infertilitas perempuan obesitas.Metode: Penelitian ini menggunakan desain potong lintang. Penelitian dilakukan di Poliklinik Bagian Obstetri dan Ginekologi RSUP Dr. M. Djamil Padang dan RS Islam Ibnu Sina Padang sejak bulan Februari 2017 – Januari 2019. Populasi pada penelitian ini adalah semua pasien yang mengalami obesitas pada perempuan usia reproduksi dengan keluhan infertilitas dengan jumlah sampel sebanyak 27 orang. Teknik pengambilan sampel dengan consecutive sampling. Analisis data dilakukan secara univariat dan bivariat dengan menggunakan uji korelasi pearson. Hasil: Hasil penelitian diketahui kurang dari separuh responden mengalami resistensi insulin dengan nilai HOMA-IR &gt; 2,5 (22,2%) dan lebih dari separuh responden tidak mengalami resistensi insulin dengan nilai HOMA-IR &lt; 2,5 (77,8%). Terdapat korelasi resistensi insulin dengan indeks massa tubuh pada infertilitas perempuan obesitas (p&lt;0,05) dengan kekuatan hubungan kuat.Kesimpulan: Terdapat korelasi resistensi insulin dengan indeks massa tubuh pada infertilitas perempuan obesitas.Kata kunci: infertilitas, obesitas, resistensi Insulin.

RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women.

Retinol‐binding protein‐4 (RBP4) is elevated in serum and adipose tissue (AT) in obesity‐induced insulin resistance and correlates inversely with insulin‐stimulated glucose disposal. But its role in insulin‐mediated suppression of lipolysis, free fatty acids (FFA), and endogenous glucose production (EGP) in humans is unknown. RBP4 mRNA or protein levels were higher in liver, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in morbidly obese subjects undergoing Roux‐en‐Y gastric bypass surgery compared to lean controls undergoing elective laparoscopic cholecystectomy. RBP4 mRNA expression in SAT correlated with the expression of several macrophage and other inflammation markers. Serum RBP4 levels correlated inversely with glucose disposal and insulin‐mediated suppression of lipolysis, FFA, and EGP. Mechanistically, RBP4 treatment of human adipocytes in vitro directly stimulated basal lipolysis. Treatment of adipocytes with conditioned media from RBP4‐activated macrophages markedly increased basal lipolysis and impaired insulin‐mediated lipolysis suppression. RBP4 treatment of macrophages increased TNFα production. These data suggest that elevated serum or adipose tissue RBP4 levels in morbidly obese subjects may cause hepatic and systemic insulin resistance by stimulating basal lipolysis and by activating macrophages in adipose tissue, resulting in release of pro‐inflammatory cytokines that impair lipolysis suppression. While we have demonstrated this mechanism in human adipocytes in vitro, and correlations from our flux studies in humans strongly support this, further studies are needed to determine whether this mechanism explains RBP4‐induced insulin resistance in humans.

Improvement in insulin sensitivity, but without changes in liver enzymes in obese women after 12 weeks of a walking exercise program with self-selected intensity

Obesity is related to negative changes in insulin resistance and liver enzymes and is associated with the risk factor for the development of type II diabetes mellitus and nonalcoholic fatty liver disease. A number of studies have demonstrated that aerobic exercise shows promise for disease prevention and treatment in this population. The objective of the present study was to evaluate the effect of a walking exercise program with self-selected intensity on insulin resistance and liver enzymes in obese women. Forty-eight obese women (47.8 ± 8.4 years; 88.1 ± 12.0 kg; 158.0 ± 0.1 cm) were divided into two groups: control group (CG; n = 23) and self-selected walking group (SSWG; n = 25). Before and after the exercise program, all subjects underwent anthropometric measurements and blood samples were collected. The intervention consisted of a walking exercise program with self-selected intensity for 12 weeks (3 times/week, totalizing 36 sessions). After the exercise program, fasting glucose, fasting insulin, and HOMA improved only in the SSWG (p 0.05). In addition, there were no differences in liver enzymes after the intervention in both groups (p > 0.05). The results support that a walking exercise program with self-selected intensity improved insulin resistance in obese women. Thus, exercise programs with self-selected intensity seem to be an interesting alternative for improving health and preventing diseases.

Estrogen receptor-α in female skeletal muscle is not required for regulation of muscle insulin sensitivity and mitochondrial regulation

ObjectiveEstrogen receptor-α (ERα) is a nuclear receptor family member thought to substantially contribute to the metabolic regulation of skeletal muscle. However, previous mouse models utilized to assess the necessity of ERα signaling in skeletal muscle were confounded by altered developmental programming and/or influenced by secondary effects, making it difficult to assign a causal role for ERα. The objective of this study was to determine the role of skeletal muscle ERα in regulating metabolism in the absence of confounding factors of development. MethodsA novel mouse model was developed allowing for induced deletion of ERα in adult female skeletal muscle (ERαKOism). ERαshRNA was also used to knockdown ERα (ERαKD) in human myotubes cultured from primary human skeletal muscle cells isolated from muscle biopsies from healthy and obese insulin-resistant women. ResultsTwelve weeks of HFD exposure had no differential effects on body composition, VO2, VCO2, RER, energy expenditure, and activity counts across genotypes. Although ERαKOism mice exhibited greater glucose intolerance than wild-type (WT) mice after chronic HFD, ex vivo skeletal muscle glucose uptake was not impaired in the ERαKOism mice. Expression of pro-inflammatory genes was altered in the skeletal muscle of the ERαKOism, but the concentrations of these inflammatory markers in the systemic circulation were either lower or remained similar to the WT mice. Finally, skeletal muscle mitochondrial respiratory capacity, oxidative phosphorylation efficiency, and H2O2 emission potential was not affected in the ERαKOism mice. ERαKD in human skeletal muscle cells neither altered differentiation capacity nor caused severe deficits in mitochondrial respiratory capacity. ConclusionsCollectively, these results suggest that ERα function is superfluous in protecting against HFD-induced skeletal muscle metabolic derangements after postnatal development is complete.

Weight loss and fitness intervention increase markers of hepatic bile acid (BA) synthesis, while reducing serum total BA concentrations in sedentary, obese insulin resistant women

Beyond adipose and muscle, excerise has profound effects in other metabolically‐important tissues including the liver. Bile acids (BAs) are synthesized from cholesterol via the rate‐limiting enzyme cholesterol 7 alpha‐hydroxylase (CYP7A1) and contribute to the solubilization and absorption of lipid soluble nutrients, and serve as important signaling molecules capable of systemic endocrine function. Circulating BA are known to be higher in obesity and insulin resistance, but effects following exercise and diet‐induced weight loss are unknown. To test if improved fitness and weight loss influence bile acid metabolism and homeostasis, we measured fasting serum concentrations of total BAs (conjugated and free forms of primary and secondary BAs) in sedentary, obese insulin‐resistant women (N=12) before and after a ~14 wk weight loss and exercise intervention [Campell et al. 2014, PLoS One, 9: e84260]. In addition, serum FGF19 (a regulator of BA synthesis) and 7‐alpha‐hydroxy‐cholesten‐3‐one (C4, a verified marker of CYP7A1 enzymatic acitivity) were measured by ELISA and LC‐MS, respectively. Using mixed‐model analyses and the change in relative VO2peak (mL/min/kg) as a covariate, we observed a significant decrease (~30%) in total serum BAs post‐intervention relative to pre‐intervention samples. Corresponding to the decrease in total BAs, fasting serum concentrations of C4 were 55% higher post‐intervention relative to the matched pre‐intervention samples (P=0.004). Interestingly, we observed no changes in serum FGF19. These data suggest that weight loss and/or improved fitness altered BA metabolism marked by increased hepatic BA synthesis and reduced serum BA. The underlying mechanisms remain to be determined, but work from our preclinical rodent models supports the idea that increased BA metabolic flux is linked to enhanced hepatic mitochondrial function.Support or Funding InformationThis work was supported by USDA Projects 6026‐51000‐010‐05S and 2032‐51530‐022‐00D, and NIH‐NIDDK R01DK078328 and NIDDK U24 DK097154.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cross-Fit 운동프로그램이 비만 여성의 신체구성, 혈중지질 및 인슐린 저항성에 미치는 영향

Cross-Fit 운동프로그램이 비만 여성의 신체구성, 혈중지질 및 인슐린 저항성에 미치는 영향

Plasma ferritin concentration is positively associated with in vivo fatty acid mobilization and insulin resistance in obese women

What is the central question of this study? Do obese women with relatively high whole-body iron stores exhibit elevated in vivo rates of fatty acid (FA) release from adipose tissue compared with a well-matched cohort of obese women with relatively low iron stores? What is the main finding and its importance? Obese women with high plasma [ferritin] (a marker of whole-body iron stores) had greater FA mobilization, lipolytic activation in adipose tissue and insulin resistance (IR) compared with obese women with lower plasma [ferritin]. Given that elevated FA mobilization is intimately linked with the development of IR, these findings suggest that elevated iron stores might contribute to IR in obesity by increasing systemic FA availability. High rates of fatty acid (FA) mobilization from adipose tissue are associated with insulin resistance (IR) in obesity. In vitro evidence suggests that iron stimulates lipolysis in adipocytes, but whether iron is related to in vivo FA mobilization is unknown. We hypothesized that plasma ferritin concentration ([ferritin]), a marker of body iron stores, would be positively associated with FA mobilization. We measured [ferritin], the rate of appearance of FA in the systemic circulation (FA Ra; stable isotope dilution), key adipose tissue lipolytic proteins and IR (hyperinsulinaemic-euglycaemic clamp) in 20 obese, premenopausal women. [Ferritin] was correlated with FA Ra (r=0.65; P=0.002) and IR (r=0.57; P=0.008); these relationships remained significant after controlling for body mass index and plasma [C-reactive protein] (a marker of systemic inflammation) in multiple regression analyses. We then stratified subjects into tertiles based on [ferritin] to compare subjects with 'High-ferritin' versus 'Low-ferritin'. Plasma [hepcidin] was more than fivefold greater (P<0.05) in the High-ferritin versus Low-ferritin group, but there was no difference in plasma [C-reactive protein] between groups, indicating that the large difference in plasma [ferritin] reflects a difference in iron stores, not systemic inflammation. We found that FA Ra, adipose protein abundance of hormone-sensitive lipase and adipose triglyceride lipase, and IR were significantly greater in subjects with High-ferritin versus Low-ferritin (all P<0.05). These data provide the first evidence linking iron and in vivo FA mobilization and suggest that elevated iron stores might contribute to IR in obesity by increasing systemic FA availability.

Enhanced ANGPTL2 expression in adipose tissues and its association with insulin resistance in obese women

Angiopoietin-like protein 2 has been proposed to be a key mediator linking obesity and insulin resistance. However, no detailed study of ANGPTL2 expression in human adipose tissues has yet been reported. To investigate the pattern and regulation of ANGPTL2 expression in human adipose tissues in obesity and its related diseases, we recruited 32 non-diabetic and 13 type 2 diabetic obese women and 32 normal-weight women. ANGPTL2 mRNA was expressed at a similar level in visceral and subcutaneous adipose tissues. Adipose tissue ANGPTL2 mRNA was much higher in obese patients. Adipose tissue ANGPTL2 mRNA and serum ANGPTL2 levels showed strong associations with metabolic parameters associated with insulin resistance. In adipose tissue, ANGPTL2 mRNA was closely correlated with the expression of genes involved in inflammation and ER stress. ANGPTL2 mRNA was principally expressed in adipocytes, and its expression was markedly higher in the adipocyte but non-adipocyte fraction of obese adipose tissues. Culture of human adipocytes under conditions mimicking the microenvironment of obese adipose tissue (especially, increased ER stress) stimulated ANGPTL2 gene expression and secretion. In addition, co-culture of adipocytes and macrophages suggested that ANGPTL2 excessively produced by adipocytes, may contribute inflammation and remodeling in obese adipose tissues, thereby promoting insulin resistance.

Lower Ectopic Fat Accumulation in Obese Women May Help Explain Sex Differences in the Magnitude of Insulin Resistance

Accumulating evidence suggests obese women maintain higher insulin sensitivity than obese men, but factors underlying this sex difference in insulin resistance remain unclear. We recently developed a semi-automated method for quantifying visceral and hepatic fat using advanced chemical shift-encoded magnetic resonance imaging (MRI). Using this method, we explored whether sex differences in ectopic fat accumulation may contribute to differences in insulin resistance. Twenty-one obese women (32 ± 6 year, 34.5 ± 3.1 kg/m2, 43.1 ± 5.5 kg fat mass (FM)) and a well-matched cohort of fifteen obese men (29 ± 6 year, 34.5 ± 3.3 kg/m2, 42.0 ± 7.8 kg FM) underwent an MRI scan during which 5mm axial slices were acquired from the abdominal region. Using 3D Slicer software, visceral fat area was quantified on three axial slices from the L2-L3 vertebrae region and averaged. Hepatic fat was quantified as the average percentage fat from three axial slices of the liver. On a separate day, subjects underwent a hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity. Compared with men, women had lower hepatic (4.2 ± 5.5 vs. 13.1 ± 9.7%, p&amp;lt;0.001) and visceral (114 ± 49 vs. 201 ± 87 cm2, p&amp;lt;0.001) fat, which corresponded with higher insulin sensitivity (Glucose infusion rate during clamp [GIR]: 514 ± 330 vs. 263 ± 134 umol/kgFFM/SSI/min, p&amp;lt;0.05). To further examine the relationship between ectopic lipid accumulation and insulin resistance, we stratified subjects into tertiles by hepatic fat content (n=12 per group). Interestingly, nearly all subjects in the lowest tertile for hepatic fat (1.1 ± 0.6%) were women, and when compared to the highest hepatic fat tertile (17.7 ± 8.2%), they also had lower visceral fat (101 ± 61 vs. 214 ± 83 cm2, p&amp;lt;0.001) and importantly, were also more insulin sensitive (GIR: 626 ± 350 vs. 279 ± 238 umol/kgFFM/SSI/min, p&amp;lt;0.05). Our findings suggest lower ectopic fat deposition may help explain the lower degree of insulin resistance in obese women compared with men. Disclosure J.B. Gillen: None. B.J. Ryan: None. R.A. Gioscia-Ryan: None. A. Ludzki: None. T.L. Chenevert: None. J.F. Horowitz: None.

Aberrant DNA Methylation Involved in Obese Women with Systemic Insulin Resistance.

BackgroundEpigenetics has been recognized as a significant regulator in many diseases. White adipose tissue (WAT) epigenetic dysregulation is associated with systemic insulin resistance (IR). The aim of this study was to survey the differential methylation of genes in obese women with systemic insulin resistance by DNA methylation microarray.MethodsThe genome-wide methylation profile of systemic insulin resistant obese women was obtained from Gene Expression Omnibus database. After data preprocessing, differing methylation patterns between insulin resistant and sensitive obese women were identified by Student’s t-test and methylation value differences. Network analysis was then performed to reveal co-regulated genes of differentially methylated genes. Functional analysis was also implemented to reveal the underlying biological processes related to systemic insulin resistance in obese women.ResultsRelative to insulin sensitive obese women, we initially screened 10,874 differentially methylated CpGs, including 7402 hyper-methylated sites and 6073 hypo-methylated CpGs. Our analysis identified 4 significantly differentially methylated genes, including SMYD3, UST, BCL11A, and BAI3. Network and functional analyses found that these differentially methylated genes were mainly involved in chondroitin and dermatan sulfate biosynthetic processes.ConclusionBased on our study, we propose several epigenetic biomarkers that may be related to obesity-associated insulin resistance. Our results provide new insights into the epigenetic regulation of disease etiology and also identify novel targets for insulin resistance treatment in obese women.

Improved glucose and IL-6 by aerobic training despite no change in insulin and insulin resistance in obese women

Background: Regular physical activity is recognized as a non-pharmacological treatment of inflammation and glycemic profile. Objectives: This exercise aimed to determine the effect of aerobic training on serum interleukin-6 (IL-6), glucose and insulin resistance in obese females. Patients and Methods: Thirty-two middle-aged obese women (body mass index [BMI], 32 ± 3 kg/m2) aged 35 to 45 years were randomly assigned to exercise (aerobic training, n=16) and control (n=16) groups. Exercise subjects were completed a 12 weeks aerobic training program as 3 sessions per week at 60%-80% of HRmax and control subjects received no training. Pre- and post-training of fasting serum IL-6, insulin, insulin resistance, and glucose concentration were measured and compared between 2 groups. Results were compared using t test at a significance level of P&lt;0.05. Results: Exercise group obtained significant decreases in BMI, body fat %, and abdominal obesity as well as the concentrations of serum IL-6 and fasting glucose (P&lt;0.05). No significant difference was observed between pre- and post-training of insulin and insulin resistance in the exercise group (P &gt;0.05). There were no alterations in these variables in the control group (P&gt;0.05). Conclusions: These data suggest that aerobic training may improve glycemic profile in absence of change in insulin resistance of women with abdominal obesity

Endurance exercise training decreased serum levels of surfactant protein D and improved aerobic fitness of obese women with type-2 diabetes

BackgroundSurfactant protein D (SP-D) is a member of the collectin family and is an important component of the pulmonary innate host defense. To find the relationship between exercise training and SP-D in diabetes, we examined the possible effects of a 10-week endurance exercise-training program on serum levels of SP-D, leptin, lipid profile and insulin resistance in obese women with type-2 diabetes mellitus (T2DM).MethodsTwenty-two obese women with T2DM were randomly assigned to either exercise training (ET) or control (C) group. A subject dropped from ET group due to personal reasons and 1 subject dropped from C group due to commitment to experiments conditions. A total of twenty obese women with T2DM were randomly assigned into endurance exercise training (ET = 10) and control (C = 10) groups. The training group underwent a progressive endurance-training program for 10 weeks (running on a treadmill for 30–55 min/day at 50–75% heart rate reserve) and the control group did not participate in any exercise program. Venous blood samples were collected from both groups before and 72 h after the last session of exercise training for analysis of serum SP-D, leptin, lipid profile, glucose and insulin. Data were analyzed using 2 (group: control, endurance training) × 2 (time: pre, post) ANOVA with repeated measures on the second factor. Absolute changes from rest (∆ baseline) values were calculated according to the following formula: ((measure-baseline)·baseline-1)·100. Percent change between groups was analyzed using independent t-tests (p < 0.05). All analyses were completed using SPSS 19.ResultsThe serum SP-D levels were decreased after exercise training in ET (∆ = − 78.78 ± 17.14%, p = 0.001) when compare to C (∆ = 9.41 ± 4.75%). Obese diabetic women in the ET group showed significantly lower serum leptin levels (8053.27 ± 878.7 pg/ml, ∆ = − 26.97 ± 16.41%) when compared with women in the control group (9885.5 ± 696 pg/ml, ∆ = 7.02 ± 3.46%, p = 0.003). Fasting glucose was favorably and significantly affected by the intervention (ET ∆ = − 17.01 ± 12.74%, Control ∆ = 15.47 ± 7.32%, p = 0.011). VO2max as an index of aerobic fitness was significantly increased after 10-weeks of endurance exercise training (ET ∆ = 19.29 ± 6.18%).ConclusionsEndurance exercise training with improvement in aerobic fitness induced a significant reduction of serum SP-D levels in obese women with T2DM.