The obesity epidemic has resulted in an exponential increase in obesity-related disorders
including type 2 diabetes, dyslipidemia and cardiovascular disease. The associated morbidity
and mortality have major consequences both at an individual as well as on the socioeconomical
level. Thus, the development of novel therapies aimed at reducing the development of obesity
is highly warranted. Brown adipose tissue (BAT) recently emerged as a novel player in energy
expenditure in humans as it combusts fatty acids towards heat. Interestingly, obese subjects
have less BAT as compared to lean subjects and activation of BAT by means of intermittent
cold exposure reduces fat mass. Therefore, BAT is considered a promising novel target to
reduce obesity and associated disorders. As cold exposure is not the most desired therapeutic
strategy for humans, current pre-clinical research focuses on pharmacological activation of
BAT.
Interestingly, the investigators have recently shown that central agonism of the receptor for
the incretin hormone glucacon-like peptide-1 (GLP-1) results in activation of BAT in mice.
One of the currently used anti-diabetic drugs that enhances GLP-1 availability is Sitagliptin
(STG). Interestingly, STG also reduces body weight and plasma triglyceride (TG) levels in
type 2 diabetes mellitus (T2DM) patients. The mechanism underlying these beneficial metabolic
effects is currently unknown. The investigators hypothesize that STG enhances BAT activation,
thereby increasing energy expenditure and combustion of TG-derived fatty acids, resulting in
lowering of plasma TG levels and body weight.
To this end, the investigators will perform a randomized double-blinded placebo-controlled
study in which 30 male Dutch Caucasian adults aged 35-50 years with moderate obesity and
pre-diabetes are included. Subjects will be treated for 12 weeks with STG or placebo. Before
and after treatment, the investigators will determine BAT volume and total BAT activity via
cold-induced 18F-FDG PET-CT scans, resting energy expenditure via indirect calorimetry using
ventilated hoods, body weight, and body composition via DEXA scan. Furthermore, before and
after treatment, blood samples will be taken to measure plasma lipids, glucose and insulin
levels.
This study will offer valuable novel insight in the effects of pharmacological activation of
BAT in human obese subjects.