Obesity
Conditions
Keywords
Brown adipose tissue, Gut peptides, Meal-induced thermogenesis, Gut-BAT-brain axis
Brief summary
This study will investigate how the acute intake of foods with high and low hedonic reward differentially affects brown adipose tissue and the interplay between gut peptides, brown fat, and the brain (gut-BAT-brain axis).
Detailed description
Background: The prevalence of obesity is alarmingly high and contributes to the dysfunction of other metabolic organs and tissues, increasing the risk of cardiometabolic diseases. Food products rich in sugar, sodium, and saturated fatty acids, i.e., with high hedonic reward, are shown to disrupt energy homeostasis by overriding the homeostatic control of food intake, promoting body weight gain. Contrary to white adipose tissue, brown adipose tissue uses glucose and triglycerides as fuel to dissipate energy as heat and has been considered an essential target for combating obesity. Recently, it has been shown that meal-induced thermogenesis (MIT) is associated with BAT function and that the postprandial secretion of secretin plays a role in BAT activation and satiety. Therefore, we hypothesize that foods with different degrees of hedonic reward (i.e high-palatable foods) affect the gut-BAT-brain axis, modulating energy homeostasis. Moreover, it differentially affects lean and obese individuals. Methods: This crossover clinical trial consists of two acute postprandial tests (low versus high-hedonic reward meals) with two weeks of washout. Thirty participants (15 lean and 15 with overweight/obesity) will undergo PET/CT scans with short-living radiotracers (\[15O\]-O2, \[15O\]-H2O PET/CT) before and after consumption of the two test meals to analyze BAT function. After food intake, one \[11C\]-carfentanil PET/CT will be carried out to understand the role of the brain in the gut-brain-BAT axis. Before and after the test meal, energy expenditure (indirect calorimetry) and circulating gut peptides will be analyzed to investigate the interplay between gut and BAT. The effect of organoleptic cues on the gut peptides and BAT will also be examined. Participants will answer dietary, behavioral, and physical activity questionnaires at the start of their participation.
Interventions
BEHAVIORALNon-palatable meal
Participants will consume a meal that corresponds to 40% of their daily resting metabolic rate and balanced diet but with low hedonic reward.
BEHAVIORALPalatable meal
Participants will consume a meal that corresponds to 40% of their daily resting metabolic rate and balanced diet but with high-hedonic reward.
Sponsors
Turku University Hospital
University of Turku
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This will be a crossover study in which participants undergo two postprandial test days with meals with high- or low-hedonic reward and two weeks of washout between interventions.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* • Males and females * Between 18 and 45 years old. * For the lean group: BMI\<25.0 kg/m2 * For the group with overweight/obesity: BMI\>27.5 kg/m2 and a waist circumference of over 94 cm (men) or 80 cm (women).
Exclusion criteria
* • Inability to have PET/CT (claustrophobia, weight \> 150 kg); * Pregnancy and pregnancy-related conditions (postpartum/lactation during the last 12 months, or planning to become pregnant soon); * Major alterations in the menstrual cycle (e.g., amenorrhea); * Use of nicotine-based products; * Hypo- or hyper- thyroidism (medical history, TSH, T3 or T4 levels out of the normal range); * Diabetes mellitus (fasting Hb1Ac \>6.5% or fasting glycaemia\>125 mg/dL) or abnormal oral glucose tolerance test (2h OGTT \> 7.8 mmol/L); * Hypertension (blood pressure \> 160/100 mmHg) or abnormal cardiovascular status (arrhythmia and/or long QTc in ECG, abnormal cardiac murmur, previous history of cardiovascular disease); * Abnormal coagulopathy (e.g., clotting abnormality); * Malignancies, immunological, autoimmune and primary/secondary immunodeficiency disorders (including or not any active treatment). * Virus or bacterial infection (both asymptomatic and symptomatic picture) within the 30 days prior to the study start; * Episode of fever or major surgery, burns and traumas within the month prior to the study start * Chronic infections requiring chronic antibiotic or anti-viral treatment * Whole blood donation in the last 3 months (\>400 mL of blood) or plans for blood donation during the entire protocol period * Weight change (intentional or not) over the last 6-months \> than 5% of body weight, or plan to lose weight during the study, * Use of any medication that, in the opinion of local clinician/researcher, would negatively affect or mitigate full participation and completion, or could influence the study results. This especially applies to the use of β or α adrenergic receptors agonists/antagonists (e.g., β-blockers). In addition, participants in use of medication for glucose control or weight loss such as GLP-1 analogs will not be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brown adipose tissue metabolism | Fasting and postprandial (30 minutes after the consumption of two different meals, 2 weeks of washout between them) | Brown adipose tissue metabolism will be assessed using 15O-O2 and 15O-H2O PET/CT, at room temperature, at fasting, after food cues, and after food intake. |
| Changes in gut peptides | Fasting and postprandial (30, 60, 90, and 120 minutes after meal intake) | Changes in gut peptides (secretin, GIP, GLP-1) from fasting to postprandial state (after intake of meals with high- or low-hedonic reward). |
| Differences in μ-opioid receptors in the human brain | The 11C-carfentanil binding potential (BP) will be analyzed 45 minutes after the consumption of the two meals (high or low-hedonic reward). The comparisons will be between the two meals. | Differences in the brain's μ-opioid receptor (MOR) system (11C-carfentanil binding potential - BP). The differences between the two meals on 11C-carfentanil BP will be analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Energy expenditure/Meal-induced thermogenesis | Changes in energy expenditure after food intake (30 minutes, 1 hour 30 minutes and 2 hours 30 minutes after food intake) | Changes in energy expenditure (from indirect calorimetry) after the intake of the two meals will be compared. |
| Visual Analogue scale (VAS) | Fasting, 30, 60, 90, and 120 minutes after food intake | Changes in VAS after food intake compared to fasting |
Countries
Finland
Contacts
STUDY_DIRECTORMilena Monfort-Pires, PhD
University of Turku
PRINCIPAL_INVESTIGATORKirsi A Virtanen, Professor
University of Turku
Outcome results
None listed