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Effect of L-arginine on energy metabolism, skeletal muscle and brown adipose tissue in South Asian and Europid prediabetic men: a randomised double-blinded crossover study.

ABSTRACT: AIMS/HYPOTHESIS:Individuals of South Asian origin are at increased risk of developing type 2 diabetes mellitus and associated comorbidities compared with Europids. Disturbances in energy metabolism may contribute to this increased risk. Skeletal muscle and possibly also brown adipose tissue (BAT) are involved in human energy metabolism and nitric oxide (NO) is suggested to play a pivotal role in regulating mitochondrial biogenesis in both tissues. We aimed to investigate the effects of 6 weeks of supplementation with L-arginine, a precursor of NO, on energy metabolism by BAT and skeletal muscle, as well as glucose metabolism in South Asian men compared with men of European descent. METHODS:We included ten Dutch South Asian men (age 46.5?±?2.8 years, BMI 30.1?±?1.1 kg/m2) and ten Dutch men of European descent, that were similar with respect to age and BMI, with prediabetes (fasting plasma glucose level 5.6-6.9 mmol/l or plasma glucose levels 2 h after an OGTT 7.8-11.1 mmol/l). Participants took either L-arginine (9 g/day) or placebo orally for 6 weeks in a randomised double-blind crossover study. Participants were eligible to participate in the study when they were aged between 40 and 55 years, had a BMI between 25 and 35 kg/m2 and did not have type 2 diabetes. Furthermore, ethnicity was defined as having four grandparents of South Asian or white European origin, respectively. Blinding of treatment was done by the pharmacy (Hankintatukku) and an independent researcher from Leiden University Medical Center randomly assigned treatments by providing a coded list. All people involved in the study as well as participants were blinded to group assignment. After each intervention, glucose tolerance was determined by OGTT and basal metabolic rate (BMR) was determined by indirect calorimetry; BAT activity was assessed by cold-induced [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography scanning. In addition, a fasting skeletal muscle biopsy was taken and analysed ex vivo for respiratory capacity using a multisubstrate protocol. The primary study endpoint was the effect of L-arginine on BAT volume and activity. RESULTS:L-Arginine did not affect BMR, [18F]FDG uptake by BAT or skeletal muscle respiration in either ethnicity. During OGTT, L-arginine lowered plasma glucose concentrations (AUC0-2 h?-?9%, p?

SUBMITTER: Boon MR

PROVIDER: S-EPMC6290676 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Effect of L-arginine on energy metabolism, skeletal muscle and brown adipose tissue in South Asian and Europid prediabetic men: a randomised double-blinded crossover study.

Boon Mariëtte R MR Hanssen Mark J W MJW Brans Boudewijn B Hülsman Cindy J M CJM Hoeks Joris J Nahon Kimberly J KJ Bakker Charlotte C van Klinken Jan B JB Havekes Bas B Schaart Gert G Jazet Ingrid M IM Rensen Patrick C N PCN van Marken Lichtenbelt Wouter D WD

Diabetologia 20181030 1

<h4>Aims/hypothesis</h4>Individuals of South Asian origin are at increased risk of developing type 2 diabetes mellitus and associated comorbidities compared with Europids. Disturbances in energy metabolism may contribute to this increased risk. Skeletal muscle and possibly also brown adipose tissue (BAT) are involved in human energy metabolism and nitric oxide (NO) is suggested to play a pivotal role in regulating mitochondrial biogenesis in both tissues. We aimed to investigate the effects of 6 ...[more]

PMID: 30377712

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Project description:A South Asian (SA) cardiovascular phenomenon exists whereby SAs have excess burden of cardiovascular disease (CVD) despite having low prevalence of recognized CVD risk factors. The aim of the current study was to determine whether perturbations in monocyte biology contribute to this phenomenon via higher circulating cell numbers, a more pro-inflammatory phenotype, and higher transmigration and adhesion. Adhesion is linked to vascular inflammation whereas transmigration is linked to tissue inflammation. SA men with (N = 10; SAs with central obesity [CO-SA]) and without (N = 10; lean SA [LE-SA]) central obesity, plus White European counterparts (N = 10; white Europeans with central obesity [CO-WE], N = 10; lean white Europeans [LE-WE]) participated. An ex vivo assay mimicking blood flow dynamics coupled to flow cytometry determined the adhesion and transmigration of monocyte subsets toward chemokine-rich media cultured from pre-adipocytes (absolute responses). Migration and adhesion were also standardized for differences in numbers of circulating monocytes between participants (relative responses). Metabolic and inflammatory markers were assessed. SAs had higher absolute (but not relative) adhesion and migration of monocytes than WEs. Central obesity was associated with higher absolute and relative adhesion and migration of monocytes. SAs had higher concentrations of all monocyte subsets compared with WEs coinciding with adverse cardiovascular-inflammatory profiles. LE-SAs had similar monocyte concentrations, transmigration, and adhesion compared with CO-WEs, corresponding with similar cardiovascular-inflammatory profiles. The study provides novel evidence for higher monocyte counts associated with higher transmigration and adhesion in SA compared with WE men. Importantly, similar monocyte biology and cardiovascular-inflammatory profiles were seen in LE-SAs compared with CO-WEs, which may contribute to the higher risk of CVD at lower body mass index experienced by SAs.

Project description:BackgroundRecent studies have shown that circulating branched-chain amino acids (BCAAs) are elevated in obese, insulin-resistant individuals. However, it is not known if supplementation of additional BCAAs will further impair glucose metabolism.ObjectivesThe aim of this pilot study was to determine the effects of BCAA supplementation on glucose metabolism in obese, prediabetic individuals.MethodsThis is a randomized crossover study involving 12 obese individuals with prediabetes. Participants were randomly assigned to receive a daily supplement containing either 20 g BCAA or protein low in BCAAs for 4 wk with a 2-wk washout in between. At each visit, an oral-glucose-tolerance test (OGTT) was performed. Collected blood samples were used to measure glucose, insulin, and insulin resistance-associated biomarkers.ResultsBCAA supplementation tended to decrease the plasma glucose area under the curve (AUC) measured by the OGTT (AUC percentage change from supplementation baseline, BCAA: -3.3% ± 3%; low-BCAA: 10.0% ± 6%; P = 0.08). However, BCAA supplementation did not affect plasma insulin during OGTT challenge (BCAA: -3.9% ± 8%; low-BCAA: 14.8% ± 10%; P = 0.28). The plasma concentrations of nerve growth factor (BCAA: 4.0 ± 1 pg/mL; low-BCAA: 5.7 ± 1 pg/mL; P = 0.01) and monocyte chemoattractant protein-1 (BCAA: -0.4% ± 9%; low-BCAA: 29.0% ± 18%; P = 0.02) were significantly lowered by BCAA supplementation compared to low-BCAA control. Plasma interleukin 1β was significantly elevated by BCAA supplementation (BCAA: 231.4% ± 187%; low-BCAA: 20.6% ± 33%; P = 0.05). BCAA supplementation did not affect the circulating concentrations of the BCAAs leucine (BCAA: 9.0% ± 12%; low-BCAA: 9.2% ± 11%), valine (BCAA: 9.1% ± 11%; low-BCAA: 12.0% ± 13%), or isoleucine (BCAA: 2.5% ± 11%; low-BCAA: 7.3% ± 11%).ConclusionsOur data suggest that BCAA supplementation did not impair glucose metabolism in obese, prediabetic subjects. Further studies are needed to confirm the results seen in the present study. This study was registered at clinicaltrials.gov as NCT03715010.

Dataset Information

Effect of L-arginine on energy metabolism, skeletal muscle and brown adipose tissue in South Asian and Europid prediabetic men: a randomised double-blinded crossover study.

Publications

Effect of L-arginine on energy metabolism, skeletal muscle and brown adipose tissue in South Asian and Europid prediabetic men: a randomised double-blinded crossover study.

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