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Scottsdale, AZ, United States

Gonzalez-Garcia Z.M.,Phoenix Childrens Hospital | Kullo I.J.,Mayo Medical School | Coletta D.K.,Mayo Center for Metabolic and Vascular Biology | Coletta D.K.,Arizona State University | And 5 more authors.
American Journal of Human Biology | Year: 2015

Objective: To examine associations between circulating levels of the bone-derived protein osteocalcin (OC) and type 2 diabetes (T2D) risk in Latino children and adults. Methods: Serum OC was measured in 136 children and 531 adults who had the following T2D risk factors assessed, body mass index (BMI), Hemoglobin A1c (HbA1c), fasting and 2-hour glucose during an oral glucose tolerance test. Results: OC was significantly higher in children than adults (209.0±12.1 vs. 41.0±0.9 ng/ml, p<0.0001). In adults, OC was inversely associated (all p<0.001) with BMI (r=-0.2), HbA1c (r=-0.2), fasting glucose (r=-0.16), and 2-hour glucose (r=-0.21), while there were no significant associations in children. There was a stepwise decrease in OC with increasing dysglycemia in adults, normoglycemic (44.1±1.3 ng/ml), prediabetic (39.3±1.3 ng/ml), and T2D (31.8±1.2 ng/ml), (p<0.0001), whereas there were no differences between normal and prediabetic youth (195.7±16.1 vs. 194.7±25.8 ng/ml, p=0.3). Conclusions: OC was inversely associated with T2D risk in Latino adults; however, this pattern was not observed in children. Am. J. Hum. Biol. 27:859-861, 2015. © 2015 Wiley Periodicals, Inc. Source

Shaibi G.Q.,Kinesiology Program | Shaibi G.Q.,Mayo Center for Metabolic and Vascular Biology | Coletta D.K.,Mayo Center for Metabolic and Vascular Biology | Coletta D.K.,Arizona State University | And 2 more authors.
Clinical and Translational Science | Year: 2013

Background: Latinos are disproportionately impacted by obesity and type 2 diabetes but remain underrepresented in biomedical research. Therefore, the purpose of this project was to develop a research registry and biorepository to examine cardiometabolic disease risk in the Latino community of Phoenix, Arizona. The overarching goal was to establish the research infrastructure that would encourage transdisciplinary research regarding the biocultural mechanisms of obesity-related health disparities and facilitate access to this research for the Latino community. Methods: Prior to recruitment, key stakeholders from the local Latino community were engaged to develop a broad rapport within the community and seek advice regarding recruitment, enrollment, and follow-up. Self-identified community-dwelling Latinos underwent a comprehensive cardiometabolic health assessment that included anthropometrics, a fasting laboratory panel, and a 2-hour oral glucose tolerance test with measures of insulin and glucose to estimate insulin action and secretion. Separate consent was requested for future contact and banking of serum, DNA, and RNA. Research collaborations were sought out based on the cultural and metabolic profile of participants, faculty research agendas, and the potential for generating hypotheses. Results: A total of 667 participants (20.4% children, and 79.6% adults) were enrolled with 97% consenting to the registry and 94% to banking of samples. The prevalence of overweight/obesity was 50% in children and 81% in adults. Nearly 20% of children and more than 45% of the adults exhibited some degree of hyperglycemia. To date, more than 15 research projects have been supported through this infrastructure and have included projects on the molecular biology of insulin resistance to the sociocultural determinants of health behaviors and outcomes. Conclusions: The high prevalence of obesity and cardiometabolic disease risk factors coupled with the overwhelming majority of participants consenting to be re-contacted, highlights the importance of supporting research infrastructure to generate hypotheses about obesity-related health in Latinos. Future studies that stem from the initial project will likely advance the limited understanding regarding the biocultural determinants of health disparities in the Latino community. © 2013 Wiley Periodicals, Inc.. Source

Day S.E.,Arizona State University | Coletta R.L.,Arizona State University | Campbell L.E.,Arizona State University | Dinu V.,Arizona State University | And 6 more authors.
Clinical Epigenetics | Year: 2016

Background: Obesity is a metabolic disease caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are incompletely understood. The aim of our study was to investigate the role of skeletal muscle DNA methylation in combination with transcriptomic changes in obesity. Results: Muscle biopsies were obtained basally from lean (n = 12; BMI = 23.4 ± 0.7 kg/m2) and obese (n = 10; BMI = 32.9 ± 0.7 kg/m2) participants in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing (RRBS) next-generation methylation and microarray analyses on DNA and RNA isolated from vastus lateralis muscle biopsies. There were 13,130 differentially methylated cytosines (DMC; uncorrected P < 0.05) that were altered in the promoter and untranslated (5' and 3'UTR) regions in the obese versus lean analysis. Microarray analysis revealed 99 probes that were significantly (corrected P < 0.05) altered. Of these, 12 genes (encompassing 22 methylation sites) demonstrated a negative relationship between gene expression and DNA methylation. Specifically, sorbin and SH3 domain containing 3 (SORBS3) which codes for the adapter protein vinexin was significantly decreased in gene expression (fold change −1.9) and had nine DMCs that were significantly increased in methylation in obesity (methylation differences ranged from 5.0 to 24.4 %). Moreover, differentially methylated region (DMR) analysis identified a region in the 5'UTR (Chr.8:22,423,530–22,423,569) of SORBS3 that was increased in methylation by 11.2 % in the obese group. The negative relationship observed between DNA methylation and gene expression for SORBS3 was validated by a site-specific sequencing approach, pyrosequencing, and qRT-PCR. Additionally, we performed transcription factor binding analysis and identified a number of transcription factors whose binding to the differentially methylated sites or region may contribute to obesity. Conclusions: These results demonstrate that obesity alters the epigenome through DNA methylation and highlights novel transcriptomic changes in SORBS3 in skeletal muscle. © 2016, The Author(s). Source

Kim J.Y.,Arizona State University | Campbell L.E.,Arizona State University | Campbell L.E.,Mayo Center for Metabolic and Vascular Biology | Shaibi G.Q.,Arizona State University | And 4 more authors.
Pediatric Obesity | Year: 2015

Background/Objectives Low-grade inflammation is an underlying feature of obesity and identifying inflammatory markers is crucial to understanding this disease. Therefore, the purpose of this study was twofold: (i) to perform a global microarray analysis and (ii) to investigate the role of lactoferrin (LTF), one of the most altered genes, in relation to obesity in Latino youth. Methods Non-diabetic Latino youth (71 males/92 females; 15.6 ± 3.2 years) were studied. A subset of 39 participants was randomly selected for global microarray analysis profiling from the whole blood sample. Serum LTF was compared between lean (n = 78) and overweight/obese (n = 85) participants. Results Microarray analysis revealed that a total of 1870 probes were altered in expression ≥1.2-fold and P < 0.05 in overweight/obese participants compared with lean. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed significant enrichment for pathways including toll-like receptor (TLR) and B cell receptor signalling pathways. LTF and TLR5 were increased in expression by 2.2 and 1.5 fold, respectively, in the overweight/obese participants. Increased LTF concentrations were significantly associated with high risk of obesity-related phenotypes (all P < 0.05). Conclusions Our data suggest that increased LTF is associated with obesity risk among Latino youth. This finding is discordant to what has been shown in adults and suggests that age may modulate the association between LTF and obesity-related health. © 2014 World Obesity. Source

Yang X.,Mayo Medical School | Yang X.,Mayo Center for Metabolic and Vascular Biology | Zhang X.,Mayo Medical School | Zhang X.,Mayo Center for Metabolic and Vascular Biology | And 5 more authors.
Journal of Biological Chemistry | Year: 2011

TNF-α potently stimulates basal lipolysis in adipocytes, which may contribute to hyperlipidemia and peripheral insulin resistance in obesity. Recent studies show that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) act sequentially in catalyzing the first two steps of adipose lipolysis in response to β-adrenergic stimulation. Here, we sought to determine their functional roles in TNF-α-induced lipolysis. Silencing of ATGL expression in adipocytes almost completely abolished basal and TNF-α-induced glycerol release. In comparison, the glycerol release under the same conditions was only partially decreased upon reduction in expression of either HSL or the ATGL coactivator CGI-58. Interestingly, overexpression of ATGL restored the lipolytic rates in cells with silenced HSL or CGI-58, indicating a predominant role for ATGL. While expression of ATGL, HSL and CGI-58 remains mostly unaffected, TNF-α treatment caused a rapid abrogation of the ATGL inhibitory protein G0S2. TNF-α drastically decreased the level of G0S2 mRNA, and the level of G0S2 protein could be maintained by inhibiting proteasomal protein degradation using MG-132. Furthermore, coexpression of G0S2 was able to significantly decrease TNF-α-stimulated lipolysis mediated by overexpressed ATGL or CGI-58. We propose that the early reduction in G0S2 content is permissive for TNF-α-induced lipolysis. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Source

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