Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease

Ding, Jingzhong; Reynolds, Lindsay M.; Zeller, Tanja; Müller, Christian; Lohman, Kurt; Nicklas, Barbara J.; Kritchevsky, Stephen B.; Huang, Zhiqing; Fuente, Alberto de la; Soranzo, Nicola; Settlage, Robert E.; Chuang, Chia Chi; Howard, Timothy D.; Xu, Ning; Goodarzi, Mark O.; Chen, Y. D.Ida; Rotter, Jerome I.; Siscovick, David S.; Parks, John S.; Murphy, Susan K.; Jacobs, David R.; Post, Wendy S.; Tracy, Russell P.; Wild, Philipp S.; Blankenberg, Stefan; Hoeschele, Ina; Herrington, David M.; McCall, Charles E.; Liu, Yongmei

doi:10.2337/db14-1314

Cited by 89 publications

(79 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DHCR24 (24-dehydrocholesterol reductase) catalyzes the reduction of sterol intermediates during cholesterol synthesis. Differential methylation of SREBF1, CPT1A, ABCG1, and DHCR24 has been reported in previous EWASs of adiposity, glycemic traits, and lipids [29][30][31][71][72][73][74][75][76]. We add to the published literature and provide evidence that differential methylation at the ABCG1 locus is likely a downstream effect of BMI.…”

Section: Differential Methylation Is Identified In Loci Known To Be Isupporting

confidence: 57%

“…The majority of BMI-related CpGs (65%-85% of CpGs depending on the cohort) had mean sample CpG methylation levels between 20% and 80% (S4 Table). Fifty of the 83 replicated differentially methylated CpGs have not been previously reported in microarraybased EWASs of BMI [28][29][30][31][32][33][34][35][36] (Table 3). Age and sex interactions among the BMI EWAS findings.…”

Section: Epigenome-wide Association Study Of Bmimentioning

confidence: 99%

See 1 more Smart Citation

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

et al. 2017

View full text Add to dashboard Cite

show abstract

Section: Differential Methylation Is Identified In Loci Known To Be Isupporting

confidence: 57%

Section: Epigenome-wide Association Study Of Bmimentioning

confidence: 99%

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

et al. 2017

View full text Add to dashboard Cite

show abstract

“…This PM cholesterol accumulation and insulin resistance model is in accord with recent gene expression network studies (Ding et al. 2015; Fall et al. 2015).…”

Section: Discussionmentioning

confidence: 99%

Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western-style high-fat diet

et al. 2017

View full text Add to dashboard Cite

Insulin action and glucose disposal are enhanced by exercise, yet the mechanisms involved remain imperfectly understood. While the causes of skeletal muscle insulin resistance also remain poorly understood, new evidence suggest excess plasma membrane (PM) cholesterol may contribute by damaging the cortical filamentous actin (F‐actin) structure essential for GLUT4 glucose transporter redistribution to the PM upon insulin stimulation. Here, we investigated whether PM cholesterol toxicity was mitigated by exercise. Male C57BL/6J mice were placed on low‐fat (LF, 10% kCal) or high‐fat (HF, 45% kCal) diets for a total of 8 weeks. During the last 3 weeks of this LF/HF diet intervention, all mice were familiarized with a treadmill for 1 week and then either sham‐exercised (0 m/min, 10% grade, 50 min) or exercised (13.5 m/min, 10% grade, 50 min) daily for 2 weeks. HF‐feeding induced a significant gain in body mass by 3 weeks. Sham or chronic exercise did not affect food consumption, water intake, or body mass gain. Prior to sham and chronic exercise, “pre‐intervention” glucose tolerance tests were performed on all animals and demonstrated that HF‐fed mice were glucose intolerant. While sham exercise did not affect glucose tolerance in the LF or HF mice, exercised mice showed an improvement in glucose tolerance. Muscle from sham‐exercised HF‐fed mice showed a significant increase in PM cholesterol, loss of cortical F‐actin, and decrease in insulin‐stimulated glucose transport compared to sham‐exercised LF‐fed mice. These HF‐fed skeletal muscle membrane/cytoskeletal abnormalities and insulin resistance were improved in exercised mice. These data reveal a new therapeutic aspect of exercise being regulation of skeletal muscle PM cholesterol homeostasis. Further studies on this mechanism of insulin resistance and the benefits of exercise on its prevention are needed.

show abstract

“…Recent whole-genome transcriptome studies demonstrated different gene pathways activation in obese subjects. Lee et al [50] investigated a time-course change in gene expression in mice during 24 weeks high fat diet, and identified differential expressed gene in oxidative phosphorylation, lipid metabolism and cell cycle pathways. The authors also investigated the differences in brown adipose tissue (BAT) genes respect to white adipose tissue (WAT), reporting increased levels of leptin and adiponectin in BAT and a consequent differential immune response [50].…”

Section: Nutrigenomic Approaches To Obesitymentioning

confidence: 99%

“…Lee et al [50] investigated a time-course change in gene expression in mice during 24 weeks high fat diet, and identified differential expressed gene in oxidative phosphorylation, lipid metabolism and cell cycle pathways. The authors also investigated the differences in brown adipose tissue (BAT) genes respect to white adipose tissue (WAT), reporting increased levels of leptin and adiponectin in BAT and a consequent differential immune response [50]. A similar study measured the gene expression changes in mice WAT and liver tissues after long-term high fat diet, and confirmed a transcriptome transition in the 24 analyzed weeks, that evolved in the perturbation of lipid metabolism and immune system homeostasis [51].…”

Section: Nutrigenomic Approaches To Obesitymentioning

confidence: 99%

Potential Nutrigenomic Approaches to Reduce the High Incidence of Obesity in Qatar

Soldati¹,

Tomei²

2016

J Nutr Food Sci

View full text Add to dashboard Cite

Obesity prevalence has been growing exponentially over the last few decades, with a high impact in high-income countries, like Qatar. Several approaches are attempting to understand the causes of this phenomenon however more important is what to do to reverse the trends. Obesity is widely studied, mostly in Europe and the Unites States, and a number of studies have demonstrate the role of specific gene patterns, transcriptome and proteome pathways, and gut microbiome strains. The Omics sciences have a great potential to investigate the determinants of non-communicable diseases, such as obesity. Nutritional genomics sciences apply all the Omics approaches to address nutrition-related diseases, investigating the interaction between genes and diet. To date, few data are available from nutrigenomic studies conducted in Middle East and particularly in Qatar to help the design of targeted interventions. The high incidence of obesity and the peculiar genetic make-up of the Qatari population provide opportunities for exploring nutrigenomic approaches to help addressing the problem.

show abstract

Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease

Cited by 89 publications

References 59 publications

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western-style high-fat diet

Potential Nutrigenomic Approaches to Reduce the High Incidence of Obesity in Qatar

Contact Info

Product

Resources

About