Centre de recherche du CHUS
Sherbrooke, Quebec, J1H 5N4, Canada
NCT Number: NCT03188835
Activating brown and beige adipose tissue (herein described as BAT) has been recently recognized as a potential means to increase energy expenditure and lower blood glucose, however, BAT activity appears to be reduced with obesity, aging or Type 2 Diabetes (T2D). BAT has the unique capability to burn large amounts of sugar and fat and effectively dissipate this energy as heat due to the expression of uncoupling protein 1 (UCP1) which is controlled by a thermogenic gene program of transcription factors, co-activators and protein kinases. Thus, enhancing the thermogenic gene program may be beneficial for treating obesity and T2D. Despite the importance of BAT in regulating metabolism our understanding of the factors which suppress its metabolic activity with obesity, aging and T2D are largely unknown. Recently, it was shown that peripheral serotonin, which is regulated by the tryptophan hydroxylase 1 (Tph1), is a negative regulator of BAT metabolic activity. In addition to serotonin, other studies have indicated that pro-inflammatory stimuli may also inhibit BAT metabolic activity. These data suggest that reduced activation of BAT may be due to increases in peripheral serotonin and inflammation. Importantly, the gut microbiome has recently been recognized as an important regulator of serotonin and inflammatory pathways suggesting the observed effects of the microbiome on obesity, T2D may be mediated in part through reductions in BAT activity.
One mechanism by which the environment may impact BAT activity and the thermogenic gene program over the last 3 decades involves changes in our food supply as result of changes in agricultural production (chlorpyrifos, glyphosphate) and the addition of food additives (fructose). These agents have been reported to alter inflammation, serotonin metabolism and the gut microbiome indicating a potential bimodal (direct and indirect via the microbiome) mechanism by which they may alter the thermogenic gene program and contribute to chronic metabolic disease. Thus, our overarching hypothesis is that environmental agents and additives related to food production may contribute to the reduced metabolic activity of BAT. The objective is to identify and characterize how food production agents and additives reduce the metabolic activity of BAT.
Looking for future studies?
Notify Me20 year–35 year
Male
Interventional
Not applicable
Sherbrooke, Quebec, J1H 5N4, Canada
Each subject will follow 3 metabolic studies (A, B and C), each lasting 7.5h which includes a 3h acute cold exposure.
These studies will be almost identical: same perfusion of tracers, same number of Positron Emission Tomography (PET) acquisitions and same number of Magnetic Resonance Imaging (MRI) associated with Magnetic Resonance Spectroscopy (MRS) acquisitions .
The difference will be in the diet ingested by the subjects two weeks before each metabolic study: during protocol A, the subjects will follow an isocaloric diet; during protocol B, the subjects will follow the same isocaloric diet supplemented with a daily beverage containing +25% of energy intake from fructose; and during protocol C, the subjects will follow the same isocaloric diet supplemented with a daily beverage containing +25% of energy intake from glucose.
Stool samples will be collected for each metabolic study for microbiome flora and metabolites.
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
A 2 weeks of hypercaloric diet supplemented with fructose or glucose
Acute cold exposure using a water-conditioned cooling suit will be applied from time 0 to 180 min. At the same time mean skin temperature will be measured by 11 thermocouples.
I.v. injection of 18-fluorodeoxyglucose (18FDG) will be performed, followed by 30 min dynamic and 50 min wholebody PET/CT scanning.
i.v. injection of 11C-acetate will be performed, followed by 20 min dynamic PET/CT scanning
i.v. administration of 1.5 uCi/min of [3-3H]-glucose
i.v. administration of 0.08 umol/kg/min of [U-13C]-palmitate
i.v. administration of 0.05 µmol/kg/min of 2H-glycerol
Visceral and cervico-thoracic MRI and MRS acquisition.
Skeletal muscle activity and shivering intensity will be measured by electromyography using surface electrodes
Lean mass will be determined by dual-energy X-ray absorptiometry
VCO2 will be measured by indirect calorimetry between 15 and 20 min every hour until time 180.
Time frame: 4 months
assessed from stool samples
Time frame: 4 months
assessed from stool samples
Time frame: 4 months
will be determined using i.v. injection of 11C-acetate during dynamic PET/CT scanning
Time frame: 4 months
will be determined by radiodensity or MRS
Time frame: 4 months
will be determined using i.v. injection of 11C-acetate during dynamic PET/CT scanning
Time frame: 4 months
will be assessed using i.v. injection of 18FDG with sequential dynamic PET/CT scanning.
Time frame: 4 months
will be assessed using i.v. injection of 18FDG with static PET/CT scanning
Time frame: 4 months
will be determined using a total body CT (16 mA) followed by a PET acquisition
Time frame: 12 months
will be determined by perfusion of stable isotope tracers
Time frame: 4 months
by indirect calorimetry
Time frame: 12 months
analysed by colorimetric and Elisa tests
Université de Sherbrooke
Other
Brown Fat Energy Metabolism During Cold Exposure: Effects of Fructose- or Glucose-rich Diet in Healthy Subjects
Acronym: GB7
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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