Dataset Information

Racial differences in in vivo adipose lipid kinetics in humans.

ABSTRACT: The storage of lipids in the form of triglycerides (TGs) and the de novo synthesis (lipogenesis) of fatty acids from nonlipid precursors [de novo lipogenesis (DNL)] are important functions of adipose tissue (AT) that influence whole-body metabolism. Yet, few studies have reported in vivo estimates of adipose lipid kinetics in humans. Fifty-two women with obesity (27 African-American and 25 Caucasian; 29.7 ± 5.5 years; BMI 32.2 ± 2.8 kg/m2; 44.3 ± 4.0% body fat) were enrolled in the study. In vivo synthesis (or replacement) of TGs (fTG) as well as the synthesis of the fatty acid, palmitate [a measure of adipose DNL (fDNL)], were assessed using an 8 week incorporation of deuterium into lipids (glycerol and palmitate moieties of TGs) in subcutaneous abdominal (scABD) and subcutaneous femoral (scFEM) AT. We report, for the first time, significant race differences in both TG synthesis and absolute DNL, with Caucasians having higher fTG and fDNL as compared with African-Americans. The DNL contribution to newly synthesized TG (corrected fDNL) was not different between races. Interestingly, our findings also show that the scFEM adipose depot had higher TG replacement rates relative to the scABD. Finally, the replacement rate of TG (fTG) was negatively correlated with changes in body weight over the 8 week labeling period. Our results provide the first evidence that in vivo TG replacement (synthesis and breakdown) rates differ by ethnicity. In addition, TG turnover varies by depot location in humans, implying an increased capacity for TG storage and higher lipolytic activity in the scFEM AT.

SUBMITTER: White UA

PROVIDER: S-EPMC6121936 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Racial differences in in vivo adipose lipid kinetics in humans.

White Ursula A UA Fitch Mark D MD Beyl Robbie A RA Hellerstein Marc K MK Ravussin Eric E

Journal of lipid research 20180617 9

The storage of lipids in the form of triglycerides (TGs) and the de novo synthesis (lipogenesis) of fatty acids from nonlipid precursors [de novo lipogenesis (DNL)] are important functions of adipose tissue (AT) that influence whole-body metabolism. Yet, few studies have reported in vivo estimates of adipose lipid kinetics in humans. Fifty-two women with obesity (27 African-American and 25 Caucasian; 29.7 ± 5.5 years; BMI 32.2 ± 2.8 kg/m<sup>2</sup>; 44.3 ± 4.0% body fat) were enrolled in the st ...[more]

PMID: 29910190

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Project description:BackgroundAdipose tissue plays important roles in health and disease. Given the unique association of visceral adipose tissue with obesity-related metabolic diseases, the distribution of lipids between the major fat depots located in subcutaneous and visceral regions may shed new light on adipose tissue-specific roles in systemic metabolic perturbations.ObjectiveWe sought to characterize the lipid networks and unveil differences in the metabolic infrastructure of the 2 adipose tissues that may have functional and nutritional implications.MethodsPaired visceral and subcutaneous adipose tissue samples were obtained from 17 overweight patients undergoing elective abdominal surgery. Ultra-performance LC-MS was used to measure 18,640 adipose-derived features; 520 were putatively identified. A stem cell model for adipogenesis was used to study the functional implications of the differences found.ResultsOur analyses resulted in detailed lipid metabolic maps of the 2 major adipose tissues. They point to a higher accumulation of phosphatidylcholines, triacylglycerols, and diacylglycerols, although lower ceramide concentrations, in subcutaneous tissue. The degree of unsaturation was lower in visceral adipose tissue (VAT) phospholipids, indicating lower unsaturated fatty acid incorporation into adipose tissue. The differential abundance of phosphatidylcholines we found can be attributed at least partially to higher expression of phosphatidylethanolamine methyl transferase (PEMT). PEMT-deficient embryonic stem cells showed a dramatic decrease in adipogenesis, and the resulting adipocytes exhibited lower accumulation of lipid droplets, in line with the lower concentrations of glycerolipids in VAT. Ceramides may inhibit the expression of PEMT by increased insulin resistance, thus potentially suggesting a functional pathway that integrates ceramide, PEMT, and glycerolipid biosynthetic pathways.ConclusionsOur work unveils differential infrastructure of the lipid networks in visceral and subcutaneous adipose tissues and suggests an integrative pathway, with a discriminative flux between adipose tissues.

Project description:RATIONALE:Blacks compared with whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes; however, little is known about racial differences in CPCs. OBJECTIVE:To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction and the predictive value of CPC counts in blacks compared with whites. METHODS AND RESULTS:CPCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34+, CD133+, VEGF2R+, and CXCR4+ epitopes in 1747 subjects, mean age 58.4±13, 55% male, and 26% self-reported black. Patients presenting with acute myocardial infarction (n=91) were analyzed separately. Models were adjusted for relevant clinical variables. SDF-1? (stromal cell-derived factor-1?), VEGF (vascular endothelial growth factor), and MMP-9 (matrix metallopeptidase-9) levels were measured (n=561), and 623 patients were followed for median of 2.2 years for survival analysis. Blacks were younger, more often female, with a higher burden of cardiovascular risk, and lower CPC counts. Blacks had fewer CD34+ cells (-17.6%; [95% confidence interval (CI), -23.5% to -11.3%]; P<0.001), CD34+/CD133+ cells (-15.5%; [95% CI, -22.4% to -8.1%]; P<0.001), CD34+/CXCR4+ cells (-17.3%; [95% CI, -23.9% to -10.2%]; P<0.001), and CD34+/VEGF2R+ cells (-27.9%; [95% CI, -46.9% to -2.0%]; P=0.04) compared with whites. The association between lower CPC counts and black race was not affected by risk factors or cardiovascular disease. Results were validated in a separate cohort of 411 patients. Blacks with acute myocardial infarction had significantly fewer CPCs compared with whites ( P=0.02). Blacks had significantly lower plasma MMP-9 levels ( P<0.001) which attenuated the association between low CD34+ and black race by 19% (95% CI, 13%-33%). However, VEGF and SDF-1? levels were not significantly different between the races. Lower CD34+ counts were similarly predictive of mortality in blacks (hazard ratio, 2.83; [95% CI, 1.12-7.20]; P=0.03) and whites (hazard ratio, 1.79; [95% CI, 1.09-2.94]; P=0.02) without significant interaction. CONCLUSIONS:Black subjects have lower levels of CPCs compared with whites which is partially dependent on lower circulating MMP-9 levels. Impaired regenerative capacity is predictive of adverse outcomes in blacks and may partly account for their increased risk of cardiovascular events.

Project description:BACKGROUND:Blacks have a higher incidence of out-of-hospital sudden cardiac death (SCD) in comparison with whites. However, the racial differences in the cumulative risk of SCD and the reasons for these differences have not been assessed in large-scale community-based cohorts. The objective of this study is to compare the lifetime cumulative risk of SCD among blacks and whites, and to evaluate the risk factors that may explain racial differences in SCD risk in the general population. METHODS:This is a cohort study of 3832 blacks and 11 237 whites participating in the Atherosclerosis Risk in Communities Study (ARIC). Race was self-reported. SCD was defined as a sudden pulseless condition from a cardiac cause in a previously stable individual, and SCD cases were adjudicated by an expert committee. Cumulative incidence was computed using competing risk models. Potential mediators included demographic and socioeconomic factors, cardiovascular risk factors, presence of coronary heart disease, and electrocardiographic parameters as time-varying factors. RESULTS:The mean (SD) age was 53.6 (5.8) years for blacks and 54.4 (5.7) years for whites. During 27.4 years of follow-up, 215 blacks and 332 whites experienced SCD. The lifetime cumulative incidence of SCD at age 85 years was 9.6, 6.6, 6.5, and 2.3% for black men, black women, white men, and white women, respectively. The sex-adjusted hazard ratio for SCD comparing blacks with whites was 2.12 (95% CI, 1.79-2.51). The association was attenuated but still statistically significant in fully adjusted models (hazard ratio, 1.38; 95% CI, 1.11-1.71). In mediation analysis, known factors explained 65.3% (95% CI 37.9-92.8%) of the excess risk of SCD in blacks in comparison with whites. The single most important factor explaining this difference was income (50.5%), followed by education (19.1%), hypertension (22.1%), and diabetes mellitus (19.6%). Racial differences were evident in both genders but stronger in women than in men. CONCLUSIONS:Blacks had a much higher risk for SCD in comparison with whites, particularly among women. Income, education, and traditional risk factors explained ?65% of the race difference in SCD. The high burden of SCD and the racial-gender disparities observed in our study represent a major public health and clinical problem.

Dataset Information

Racial differences in in vivo adipose lipid kinetics in humans.

Publications

Racial differences in in vivo adipose lipid kinetics in humans.

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