L-arginine and Brown Adipose Tissue

Summary

The South Asian population is facing an epidemic of type 2 diabetes, of which the underlying cause is still unknown. It is currently hypothesized that an ethnic susceptibility towards a disturbed energy metabolism may underlie this disadvantageous metabolic phenotype. In line with this, the investigators recently discovered that Dutch South Asian subjects have 32% lower resting energy expenditure (REE) and 34% lower energy-combusting brown adipose tissue (BAT) compared to matched white Caucasians. Nitric oxide (NO) was recently shown to be crucial for BAT development and, interestingly, South Asians have diminished NO bioavailability. Thus, the disadvantageous metabolic phenotype in South Asians may be caused by diminished NO bioavailability resulting in lower BAT volume. Therefore, the investigators hypothesize that increasing NO generation in the body by administration of L-arginine, the precursor of NO, will improve their metabolic phenotype by increasing BAT volume, thereby increasing REE and clearance of triglycerides and glucose by BAT. To investigate this, the investigators will perform a randomized placebo-controlled multicenter cross-over study in moderately obese Dutch South Asians and matched white Caucasians. Subjects will receive L-arginine (9 gram/day) or placebo for 6 weeks, followed by a wash-out period of 4 weeks and then again 6 weeks of one of either treatments. At the end of both treatment periods, a cold-induced PET-CT scan will be performed. Furthermore, muscle and fat biopsies will be obtained and thermoregulation will be assessed.

Timeline

Start

2014-11

Primary completion

2015-10

Completion

2015-12

Publications

• Janssen LGM, Van Dam AD, Hanssen MJW, Kooijman S, Nahon KJ, Reinders H, Jazet IM, Van Marken Lichtenbelt WD, Rensen PCN, Appelman-Dijkstra NM, Boon MR. Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men. Diabetes Metab J. 2020 Apr;44(2):326-335. doi: 10.4093/dmj.2019.0031. Epub 2019 Oct 31.
• Boon MR, Hanssen MJW, Brans B, Hulsman CJM, Hoeks J, Nahon KJ, Bakker C, van Klinken JB, Havekes B, Schaart G, Jazet IM, Rensen PCN, van Marken Lichtenbelt WD. 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. Diabetologia. 2019 Jan;62(1):112-122. doi: 10.1007/s00125-018-4752-6. Epub 2018 Oct 30.
• Nahon KJ, Kantae V, den Haan R, Hanssen MJW, Harms AC, van der Stelt M, Hankemeier T, Jazet IM, van Marken Lichtenbelt WD, Rensen PCN, Boon MR. Gene Expression of Endocannabinoid System Components in Skeletal Muscle and Adipose Tissue of South Asians and White Caucasians with Overweight. Obesity (Silver Spring). 2018 Aug;26(8):1332-1337. doi: 10.1002/oby.22245. Epub 2018 Aug 1.

Drugs

Indications