The Effect of Brown Adipose Tissue Activation on Insulin Sensitivity in Humans
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Rutgers University
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Insulin Sensitivity
Study Overview
Brief Summary
Recent findings document the presence of active brown adipose tissue (BAT) in humans. Cold exposure via adrenergic stimulation activates BAT, which combusts significant amounts of blood glucose and free fatty acid (FFA) to produce heat. Animal studies suggest that BAT activation improves insulin sensitivity. However, the effect of cold-induced BAT activation on insulin sensitivity and glucose kinetics in humans remains unknown. The investigators' central hypothesis is that cold-induced BAT activation increases whole body insulin sensitivity in humans via augmented plasma glucose and FFA clearance. The specific aims of this study are to define the effects of prolonged (8h) cold exposure BAT activation on: insulin sensitivity (Aim 1); lipolysis and plasma glucose and FFA kinetics (Aim 2); on thermoregulation (Aim 3). Moreover, the investigators plan to investigate for alternative ways, which can activate BAT including cold water ingestion, a single meal ingestion, and a single bout of moderate intensity exercise (Aim 4). For the cold exposure study, subjects will complete 3 trials: a) 8hrs of cold exposure at their individually determined shivering threshold; b) 8hrs of cold exposure at their individually determined shivering threshold plus propranolol; c) 8hrs in thermoneutral conditions (26 - 28°C). For the rest of the arms of subjects will complete two trials: cold or tepid water ingestion, a single meal ingestion or no food ingestion, and a single bout of moderate intensity exercise or no exercise.To study the above aims, the investigators will use positron emission tomography - computed tomography, hyperinsulinemic euglycemic clamp, infusion of stable isotopes, and tissue biopsies. The findings will illuminate the role of BAT on plasma substrate regulation and insulin sensitivity and may aid in the development of lifestyle recommendations and pharmacotherapy for the prevention and treatment of diabetes and insulin resistance.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •men or women
- •18-75 years old
- •BMI 20-40 kg/m2
Exclusion Criteria
- •taking diabetes medications
- •liver/renal/endocrine/heart disease
- •obstructive disease of the gastrointestinal tract
- •impaired gag reflex or swallowing disorder
- •history of GI surgery or fenilization of esophagus
- •GI hypomotility disorder
- •thyroid or hormone replacement treatment
- •beta-blockers
- •anabolic or corticosteroids the last 6 mo
- •pregnant/lactating women
- •individuals that are likely to need PET/CT in the near future for medical reasons
- •bleeding disorders/ anemia
- •positive hepatitis or HIV screening
- •weight less than 36 kg
- •pacemaker or other implanted electromedical device
- •alcohol and drug abuse
- •tobacco use
- •impaired cognition
- •chronic obstructive pulmonary disease (COPD) or other reactive airway diseases
Arms & Interventions
Cold water consumption
Subjects will participate in two trials as part of this protocol: a) cold water (4 °C) consumption and b) tepid (36 °C) water consumption
Intervention: Cold water consumption (Other)
Cold water consumption
Subjects will participate in two trials as part of this protocol: a) cold water (4 °C) consumption and b) tepid (36 °C) water consumption
Intervention: Tepid water consumption (Other)
Meal consumption
Subjects will participate in two trials as part of this protocol: a) High calorie meal consumption and two weeks later b) no meal consumption.
Intervention: Thermoneutral Conditions (Other)
Meal consumption
Subjects will participate in two trials as part of this protocol: a) High calorie meal consumption and two weeks later b) no meal consumption.
Intervention: Meal consumption (Other)
Cold exposure
Participants will complete three studies: a) cold exposure study (above their individually determined shivering threshold ~ 16°C); b) Cold exposure plus 0.5mg/kg up to 40mg propranolol at the beginning of the metabolic study and again after 4-6 hrs; c) thermoneutral conditions (26 - 28°C).
Intervention: Cold exposure (Other)
Cold exposure
Participants will complete three studies: a) cold exposure study (above their individually determined shivering threshold ~ 16°C); b) Cold exposure plus 0.5mg/kg up to 40mg propranolol at the beginning of the metabolic study and again after 4-6 hrs; c) thermoneutral conditions (26 - 28°C).
Intervention: Cold exposure plus propranolol (Other)
Cold exposure
Participants will complete three studies: a) cold exposure study (above their individually determined shivering threshold ~ 16°C); b) Cold exposure plus 0.5mg/kg up to 40mg propranolol at the beginning of the metabolic study and again after 4-6 hrs; c) thermoneutral conditions (26 - 28°C).
Intervention: Thermoneutral Conditions (Other)
Exercise
Subjects between 18 and 35 years old will be asked to participate in two trials: a) Exercise, i.e. four times for 10 min- at 85% VO2max (maximal oxygen consumption). with 15-min breaks between each bout b) and two weeks later rest.
Intervention: Thermoneutral Conditions (Other)
Exercise
Subjects between 18 and 35 years old will be asked to participate in two trials: a) Exercise, i.e. four times for 10 min- at 85% VO2max (maximal oxygen consumption). with 15-min breaks between each bout b) and two weeks later rest.
Intervention: Exercise (Other)
Outcomes
Primary Outcomes
Insulin Sensitivity
Time Frame: After 8hrs of cold exposure or thermoneutral conditions
Insulin sensitivity will be measured using the euglycemic hyperinsulinemic insulin clamp method
Secondary Outcomes
- Metabolic profile(During the 8hr trial or on the following day)
Investigators
Labros Sidossis, Ph.D.
Professor
Rutgers University