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/hypothesisIndividuals 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.MethodsWe 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.Resultsl-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 < 0.01), insulin excursion (AUC0–2 h − 26%, p < 0.05) and peak insulin concentrations (−26%, p < 0.05) in Europid but not South Asian men. This coincided with enhanced cold-induced glucose oxidation (+44%, p < 0.05) in Europids only. Of note, in skeletal muscle biopsies several respiration states were consistently lower in South Asian men compared with Europid men.Conclusions/interpretationl-Arginine supplementation does not affect BMR, [18F]FDG uptake by BAT, or skeletal muscle mitochondrial respiration in Europid and South Asian overweight and prediabetic men. However, l-arginine improves glucose tolerance in Europids but not in South Asians. Furthermore, South Asian men have lower skeletal muscle ox...

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

“…In concordance, serum sclerostin levels positively correlated with skeletal muscle and adipose tissue insulin resistance in a hyperinsulinemic-euglycemic clamp study in human subjects with either normoglycemia or prediabetes [13]. Alternative mechanisms that may contribute to peripheral insulin resistance in South Asians are a pro-inflammatory status, including downregulation of genes involved in anti-inflammatory type 1 interferon signaling in WAT and skeletal muscle [35], lower adiponectin levels [36,37], as well as a lower skeletal muscle oxidative capacity [38] and cardiorespiratory fitness compared with white Caucasians [39].…”

Effects of dietary arginine supplementation in pregnant mares on maternal metabolism, placental structure and function and foal growth

“…In the pig, oral L-arginine supplementation during gestation increased the weight of piglets and placentas at birth 22–24 . Moreover, long-term supplementation with L-arginine has been shown to reduce glucose and insulin plasma concentrations following an oral glucose tolerance test in humans 25,26 . L-arginine supplementation could thus increase birthweight and improve maternal metabolism during pregnancy.…”

Effects of Nutrition/Diet on Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis

“…These studies showed no mean differences in SUV of BAT ( p > 0.05) following a high calorie (1622 ± 222 kcal) carbohydrate rich meal [ 31 ], a standard (545 kcal) meal [ 29 ] and during 200% overfeeding [ 45 ] ( Figure 3 ). Finally, one study [ 42 ] offered data for a meta-analysis from two different groups of participants, investigating the effects of a 6-week supplementation of L-Arginine on BAT activity, which showed no mean differences in SUV of BAT ( p > 0.05; Figure 4 ).…”

“…One RCT [40] and one CSS [41] examined the effects/associations of dietary factors on BAT activity through measurements of core and skin temperatures. Five RCTs [29,[42][43][44][45], one CSS [46], one CT [47] and one SGDS [31] studied the effects/associations of dietary elements on BAT activity using PET/CT, while a SGDS [32] used infrared camera for BAT assessments. One SGDS [48] and one CSS [49] examined the effects/associations of dietary factors on BAT activity via measurements of UCP1.…”