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Background and Aims: South Asians have an exceptionally high risk of developing cardiovascular disease compared to white Caucasians. A contributing factor might be dysfunction of high density lipoprotein (HDL). We aimed to compare HDL function in different age groups of both ethnicities., Methods and Results: HDL functionality with respect to cholesterol efflux, anti-oxidation and anti-inflammation was determined using fasting, apoB-depleted, plasma samples from South Asian and white Caucasian neonates (n = 14 each), adolescent healthy men (n = 12 each, 18-25 y), and adult overweight men (n = 12 each, 40-50 y). Adolescents were subjected to a 5-day high fat high calorie diet (HCD) and adults to an 8-day very low calorie diet (LCD). Additionally, HDL composition was measured in adolescents and adults using (1)H-NMR spectroscopy. Anti-oxidative capacity was lower in South Asian adults before LCD (19.4 ± 2.1 vs. 25.8 ± 1.2%, p = 0.045, 95%-CI = [0.1; 12.7]) and after LCD (16.4 ± 2.4 vs. 27.6 ± 2.7%, p = 0.001, 95%-CI = [4.9; 17.5]). Anti-inflammatory capacity was reduced in South Asian neonates (23.8 ± 1.2 vs. 34.9 ± 1.3%, p = 0.000001, 95%-CI = [-14.6; -7.5]), and was negatively affected by an 8-day LCD only in South Asian adults (-12.2 ± 4.3%, p = 0.005, 95%-CI = [-5.9; -1.2]). Cholesterol efflux capacity was increased in response to HCD in adolescents (South Asians: +6.3 ± 2.9%, p = 0.073, 95%-CI = [-0.02; 0.46], Caucasians: +11.8 ± 3.4%, p = 0.002, 95%-CI = [0.17;0.65]) and decreased after LCD in adults (South Asians: -10.3 ± 2.4%, p < 0.001, 95%-CI = [-0.57; -0.20], Caucasians: -13.7 ± 1.9%, p < 0.00001, 95%-CI = [-0.67; -0.33]). Although subclass analyses of HDL showed no differences between ethnicities, cholesterol efflux correlated best with cholesterol and phospholipid within small HDL compared to other HDL subclasses and constituents., Conclusion: Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk., Clinical Trial Registration: NTR 2473 (URL: http://www.trialregister.nl/)., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

During mild cold exposure, non-shivering thermogenesis increases to maintain core body temperature by increasing utilization of substrates, especially fatty acids (FA), ultimately affecting lipid-associated metabolites. We aimed to investigate whether mild cooling induces changes in other metabolites and whether this response differs between white Caucasians and South Asians, who have a disadvantageous metabolic phenotype. 12 lean male Dutch white Caucasians and 12 matched Dutch South Asians were exposed to mild cold. Before and after 100 min exposure, serum samples were collected for analysis of 163 metabolites and 27 derived parameters using high throughput metabolomics. The overall response to mild cooling between both ethnicities was not different, therefore the data were pooled. After Bonferroni correction, mild cooling significantly changed 44 of 190 (23%) metabolic parameters. Specifically, cooling increased 19 phosphatidylcholine (PC) species, only those containing very long chain FAs, and increased the total class of PC containing mono-unsaturated FAs (+12.5%). Furthermore, cooling increased 10 sphingomyelin species as well as the amino acids glutamine (+18.7%), glycine (+11.6%) and histidine (+10.6%), and decreased short-chain (C3 and C4) acylcarnitines (-17.1% and -19.4%, respectively). In conclusion, mild cooling elicits substantial effects on serum metabolites in healthy males, irrespective of white Caucasian or South Asian ethnicity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Aims: South Asians have a higher risk of developing cardiovascular disease than white Caucasians. The underlying cause is unknown, but might be related to higher cardiac susceptibility to metabolic disorders. Short-term caloric restriction (CR) can be used as a metabolic stress test to study cardiac flexibility. We assessed whether metabolic and functional cardiovascular flexibility to CR differs between South Asians and white Caucasians., Methods and Results: Cardiovascular function and myocardial triglycerides were assessed using a 1.5T-MRI/S-scanner in 12 middle-aged overweight male South Asians and 12 matched white Caucasians before and after an 8-day very low calorie diet (VLCD). At baseline South Asians were more insulin resistant than Caucasians. Cardiac dimensions were smaller, despite correction for body surface area, and pulse wave velocity (PWV) in the distal aorta was higher in South Asians. Systolic and diastolic function, myocardial triglycerides and pericardial fat did not differ significantly between groups. After the VLCD body weight reduced on average by 4.0 ± 0.2 kg. Myocardial triglycerides increased in both ethnicities by 69 ± 18%, and diastolic function decreased although this was not significant in South Asians. However, pericardial fat and PWV in the proximal and total aorta were reduced in Caucasians only., Conclusion: Myocardial triglyceride stores in middle-aged overweight and insulin resistant South Asians are as flexible and amenable to therapeutic intervention by CR as age-, sex- and BMI-matched but less insulin resistant white Caucasians. However, paracardial fat volume and PWV showed a differential effect in response to an 8-day VLCD in favor of Caucasians., Clinical Trial Registration: NTR 2473 (URL: http://www.trialregister.nl/trialreg/admin/rctsearch.asp?Term=2473)., (Copyright © 2015 Elsevier B.V. All rights reserved.)