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Beverly Hills, CA, United States

Gower B.A.,University of Alabama at Birmingham | Bergman R.,Cedars Sinai Diabetes and Obesity Research Institute | Stefanovski D.,University of Pennsylvania | Darnell B.,Clinical Research Unit | And 5 more authors.
Nutrition and Metabolism | Year: 2016

Background: Resistant starch (RS) is a type of dietary fiber that can improve glucose metabolism, but its effects may be modulated by sex or baseline insulin sensitivity. This study was designed to examine the effect of high-amylose maize resistant starch (HAM-RS2) on insulin sensitivity (SI) in women, and to determine if SI status affects the response to RS. Methods: This was a randomized, placebo-controlled, double-blind, cross-over study. Participants were 40 healthy, non-diabetic women aged 22-67 years in the normal-weight to obese BMI range (20.6-47.4 kg/m2). Two doses of HAM-RS2 were tested, 15 and 30 g per day, administered in the form of cookies. Participants were randomized to the order in which they received the experimental and placebo product. Each arm was 4 weeks, with a 4-week wash-out period in between. SI was assessed at the end of each 4-week arm of product consumption by frequently-sampled, insulin-modified, intravenous glucose tolerance test and minimal modeling. Participants were categorized as being insulin resistant (IR; SI < 7.8) or insulin sensitive (IS; SI ≥ 7.8) based on Gaussian analysis. The effect of treatment arm on SI was examined by mixed-model analysis within IR and IS sub-groups, using all available data. In addition, SI was examined by ANOVA among just those women who completed all three arms of the study with valid SI results. Results: Among IR participants, SI was on average ~16 % higher after the 30 g arm when compared to the control arm by mixed-model analysis (n = 40, P < 0.05), and tended to be 23 % higher by ANOVA among women who completed all arms (n = 23, P = 0.06). HAM-RS2 did not affect SI in IS women. Conclusion: Consumption of HAM-RS2 at 30 g/day in the form of a snack food item was associated with improved insulin sensitivity in women with insulin resistance. © 2016 Gower et al. Source


Ahlin S.,Gothenburg University | Sjoholm K.,Gothenburg University | Jacobson P.,Gothenburg University | Andersson-Assarsson J.C.,Gothenburg University | And 16 more authors.
Obesity | Year: 2013

Objective: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. Design and Methods: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. Results: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group. Conclusion: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia. Copyright © 2013 The Obesity Society. Source


Kim J.S.,University of Otago | Rizwan M.Z.,University of Otago | Clegg D.J.,Cedars Sinai Diabetes and Obesity Research Institute | Anderson G.M.,University of Otago
Endocrinology | Year: 2016

Estradiol and leptin are critical hormones in the regulation of body weight. The aim of this study was to determine whether this cross talk between leptin receptor (LepRb) and estrogen receptor-(ER) signaling is critical for estradiol's anorexigenic effects. Leprb-Cre mice were crossed with Cre-dependent Tau-green fluorescent protein (GFP) reporter, Stat3-flox or Er-flox mice to generate female mice with GFP expression, signal transducer and activator of transcription 3 (STAT3) knockout (KO), or ER KO, specifically in LepRb-expressing cells. The proportion of Leprb-GFP cells colocalizing ER was high (80%) in the preoptic area but low (10%) in the mediobasal hypothalamus, suggesting that intracellular cross talk between these receptors is minimal for metabolic regulation. To test whether estradiol enhanced arcuate leptin sensitivity, ovarectomized mice received varying levels of estradiol replacement. Increasing estrogenic states did not increase the degree of leptin-induced STAT3 phosphorylation. LepRb-specific STAT3KOmice and controls were ovarectomized and given either chronic estradiol or vehicle treatment to test whether STAT3 is required for estrogen-induced body weight suppression. Both groups of estradiol-treated mice showed an equivalent reduction in body weight and fat content compared with vehicle controls. Finally, mice lacking ER specifically in LepRb-expressing neurons also showed no increase in body weight or impairments in metabolic function compared with controls, indicating that estradiol acts independently of leptin-responsive cells to regulate body weight. However, fecundity was impaired in in Leprb-ER KO females. Contrary to the current dogma, we report that estradiol has minimal direct actions on LepRb cells in the mediodasal hypothalamus and that its anorexigenic effects can occur entirely independently of LepRb-STAT3 signaling in female mice. Copyright © 2016 by the Endocrine Society. Source


Rowe M.W.,Tethys BioScience Inc. | Bergman R.N.,Cedars Sinai Diabetes and Obesity Research Institute | Wagenknecht L.E.,Wake forest University | Kolberg J.A.,Tethys BioScience Inc.
Diabetes/Metabolism Research and Reviews | Year: 2012

Background: This study compares a previously developed Diabetes Risk Score to commonly used clinical tools for type 2 diabetes risk evaluation in the Insulin Resistance Atherosclerosis Study (IRAS) cohort, a multi-ethnic US cohort. Available as a clinical test, the PreDx® Diabetes Risk Score uses fasting concentrations of adiponectin, C-reactive protein, ferritin, interleukin-2 receptor alpha, HbA1c, glucose and insulin, plus age and gender to predict 5-year risk of diabetes. It was developed in a Northern European population. Methods: The Diabetes Risk Score was measured using archived fasting plasma specimens from 722 non-diabetic IRAS participants, 17.6% of whom developed diabetes during 5.2years median follow-up (inter-quartile range: 5.1-5.4years). The study included non-Hispanic whites (41.8%), Hispanics (34.5%) and African Americans (23.7%). Performance of the algorithm was evaluated by area under the receiver operating characteristic curve (AROC) and risk reclassification against other tools. Results: The Diabetes Risk Score discriminates participants who developed diabetes from those who did not significantly better than fasting glucose (AROC=0.763 versus 0.710, p=0.003). The Diabetes Risk Score performed equally well in subpopulations defined by race/ethnicity or gender. The Diabetes Risk Score provided a significant net reclassification improvement of 0.24 (p=0.01) when comparing predefined low/moderate/high Diabetes Risk Score categories to metabolic syndrome risk factor counting. The Diabetes Risk Score complemented the use of the oral glucose tolerance test by identifying high risk patients with impaired fasting glucose but normal glucose tolerance, 33% of whom converted. Conclusions: Measuring the Diabetes Risk Score of elevated-risk US patients could help physicians decide which patients warrant more intensive intervention. The Diabetes Risk Score performed equally well across the ethnic subpopulations present in this cohort. © 2012 John Wiley & Sons, Ltd. Source


Morselli E.,Bernardo OHiggins University | Frank A.P.,Cedars Sinai Diabetes and Obesity Research Institute | Palmer B.F.,Southwestern University | Rodriguez-Navas C.,Southwestern University | And 2 more authors.
International Journal of Obesity | Year: 2016

In this review, we discuss the observations that, following chronic high-fat diet (HFD) exposure, male mice have higher levels of saturated fatty acids (FAs) and total sphingolipids, whereas lower amounts of polyunsaturated FAs in the central nervous system (CNS) than females. Furthermore, males, when compared with female mice, have higher levels of inflammatory markers in the hypothalamus following exposure to HFD. The increase in markers of inflammation in male mice is possibly due to the reductions in proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and estrogen receptor alpha (ERα), which is not recapitulated in female mice. Consistently, hypothalamic inflammation is induced both in male and female ERα total-body knockout mice when exposed to a HFD, thus confirming the key role of ERα in the regulation of HFD-induced hypothalamic inflammation. Finally, the HFD-induced depletion of hypothalamic ERα is associated with dysregulation in metabolic homeostasis, as evidenced by reductions in glucose tolerance and decrements in myocardial function. © 2016 Macmillan Publishers Limited. Source

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