Effects of Fructose/Glucose-rich Diet on Brown Fat in Healthy Subjects (GB7)

NCT03188835 | Completed

• 1 other identifier: 2017-1459
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type2 Diabetes

Outcome Measures

Primary Outcomes (4)

• Microbiome flora

  assessed from stool samples

  4 months

• Microbiome metabolites

  assessed from stool samples

  4 months

• BAT oxidative metabolism

  will be determined using i.v. injection of 11C-acetate during dynamic PET/CT scanning

  4 months

• BAT triglyceride content

  will be determined by radiodensity or MRS

  4 months

Secondary Outcomes (7)

• BAT blood flow

  4 months

• BAT net glucose uptake

  4 months

• Whole-body glucose partitioning

  4 months

• BAT volume of metabolic activity

  4 months

• metabolites appearance rate

  12 months

Study Arms (3)

Isocaloric Diet

OTHER

Two weeks of isocaloric diet

Other: cold exposure; Radiation: 18FDG; Radiation: 11C-acetate; Radiation: [3-3H]-glucose; Other: [U-13C]-palmitate; Other: 2H-Glycerol; Device: MRI/MRS; Device: Electromyogram (EMG); Device: DXA; Device: Indirect calorimetry

Fructose diet

OTHER

Two weeks of hypercaloric diet supplemented with fructose

Dietary Supplement: Diet; Other: cold exposure; Radiation: 18FDG; Radiation: 11C-acetate; Radiation: [3-3H]-glucose; Other: [U-13C]-palmitate; Other: 2H-Glycerol; Device: MRI/MRS; Device: Electromyogram (EMG); Device: DXA; Device: Indirect calorimetry

Glucose diet

OTHER

Two weeks of hypercaloric diet supplemented with glucose

Dietary Supplement: Diet; Other: cold exposure; Radiation: 18FDG; Radiation: 11C-acetate; Radiation: [3-3H]-glucose; Other: [U-13C]-palmitate; Other: 2H-Glycerol; Device: MRI/MRS; Device: Electromyogram (EMG); Device: DXA; Device: Indirect calorimetry

Interventions

Diet DIETARY_SUPPLEMENT

A 2 weeks of hypercaloric diet supplemented with fructose or glucose

Fructose diet; Glucose diet

cold exposure OTHER

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.

Fructose diet; Glucose diet; Isocaloric Diet

18FDG RADIATION

I.v. injection of 18-fluorodeoxyglucose (18FDG) will be performed, followed by 30 min dynamic and 50 min wholebody PET/CT scanning.

Fructose diet; Glucose diet; Isocaloric Diet

11C-acetate RADIATION

i.v. injection of 11C-acetate will be performed, followed by 20 min dynamic PET/CT scanning

Fructose diet; Glucose diet; Isocaloric Diet

[3-3H]-glucose RADIATION

i.v. administration of 1.5 uCi/min of \[3-3H\]-glucose

Fructose diet; Glucose diet; Isocaloric Diet

[U-13C]-palmitate OTHER

i.v. administration of 0.08 umol/kg/min of \[U-13C\]-palmitate

Fructose diet; Glucose diet; Isocaloric Diet

2H-Glycerol OTHER

i.v. administration of 0.05 µmol/kg/min of 2H-glycerol

Fructose diet; Glucose diet; Isocaloric Diet

MRI/MRS DEVICE

Visceral and cervico-thoracic MRI and MRS acquisition.

Fructose diet; Glucose diet; Isocaloric Diet

Electromyogram (EMG) DEVICE

Skeletal muscle activity and shivering intensity will be measured by electromyography using surface electrodes

Fructose diet; Glucose diet; Isocaloric Diet

DXA DEVICE

Lean mass will be determined by dual-energy X-ray absorptiometry

Fructose diet; Glucose diet; Isocaloric Diet

Indirect calorimetry DEVICE

VCO2 will be measured by indirect calorimetry between 15 and 20 min every hour until time 180.

Fructose diet; Glucose diet; Isocaloric Diet

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects: subjects with normal glucose tolerance determined according to an oral glucose tolerance test and with a BMI \< 27 kg/m2 without first degree of familial history of type 2 diabetes (parents, siblings).

You may not qualify if:

• Plasma triglycerides \> 5.0 mmol/L at fasting;
• More than 2 alcohol consumption per day;
• More than 1 cigarette per day;
• History of total cholesterol level \> 7 mmol/L, of cardiovascular disease, hypertensive crisis;
• Treatment with fibrates, thiazolidinedione, insulin, beta-blockers or other drugs with effects on insulin resistance or lipid metabolism (exception for anti-hypertensive drugs, statins or metformin);
• Presence of a non-controlled thyroid disease, renal or hepatic disease, history of pancreatitis, bleeding diatheses, cardiovascular disease or any other serious medical conditions;
• History of serious gastrointestinal disorders (malabsorption, peptic ulcer, gastroesophageal reflux having required a surgery, etc.);
• Presence of a pacemaker;
• Have undergone of PET study or CT scan in the past year;
• Chronic administration of any medication;

Sponsors & Collaborators

• Université de Sherbrooke: lead
• McMaster University: collaborator
• University of Ottawa: collaborator

Study Sites (1)

Centre de recherche du CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (1)

• Richard G, Blondin DP, Syed SA, Rossi L, Fontes ME, Fortin M, Phoenix S, Frisch F, Dubreuil S, Guerin B, Turcotte EE, Lepage M, Surette MG, Schertzer JD, Steinberg GR, Morrison KM, Carpentier AC. High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake independently of changes in thermogenesis and the gut microbiome. Cell Rep Med. 2022 Sep 20;3(9):100742. doi: 10.1016/j.xcrm.2022.100742.

  PMID: 36130480 DERIVED

Related Links

• High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake independently of changes in thermogenesis and the gut microbiome
• Human brown adipose tissue is not enough to combat cardiometabolic diseases

MeSH Terms

Interventions

Diet; Fluorodeoxyglucose F18; carbon-11 acetate; Electromyography; Calorimetry, Indirect

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Deoxyglucose; Deoxy Sugars; Carbohydrates; Electrodiagnosis; Diagnostic Techniques and Procedures; Diagnosis; Myography; Calorimetry; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• André C. Carpentier

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: tenured professor

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 15, 2017
• Study Start: May 23, 2017
• Primary Completion: December 17, 2020
• Study Completion: April 30, 2021
• Last Updated: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)