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.