How Metabolism Affects Weight Loss and Gain

University Hospital Schleswig-Holstein20 enrolled

Overview

This study examines why some individuals with obesity have difficulty losing weight, whereas some lean individuals struggle to gain weight. The investigators will measure how the human body uses energy during a fasting period and after consumption of a specially designed, low-protein meal. By comparing these responses, the investigators aim to identify different "metabolic phenotypes" that affect weight control. Findings from this research may lead to more personalized treatments for managing weight. Participation in this study involves simple tests and basic body measurements.

This study aims to better understand why certain individuals find it difficult to lose weight while others struggle to gain weight. Investigators believe that differences in how the human body uses energy-referred to as the metabolic phenotype-may play a key role. Two groups of participants will be compared: one group includes lean individuals who have difficulty gaining weight, and the other group consists of individuals with obesity who have difficulty losing weight. Participants will undergo a series of tests designed to measure how the human body burns calories under different conditions. The study involves two main components: 1. 24-Hour Fasting Period: Participants will abstain from eating for 24 hours to observe how the body adapts by either conserving or maintaining energy expenditure. 2. Meal Test: Following the fasting period, participants will consume a specially designed, low-protein meal that simulates overeating. The investigators will measure how much additional energy is burned during digestion, a process known as diet-induced thermogenesis. A technique called indirect calorimetry will record oxygen consumption and carbon dioxide production. These measurements help calculate resting energy expenditure (REE), which refers to the calories the body burns while at rest, and any changes that occur after fasting and eating. The goal is to identify distinct metabolic patterns. Some individuals may have a "thrifty" metabolism that conserves energy, making weight loss more challenging, whereas others may have a "spendthrift" metabolism that expends more energy, potentially explaining difficulty in gaining weight. Understanding these differences could lead to more personalized and effective weight management strategies. This study is conducted under strict safety and ethical standards to ensure minimal risk to participants. By examining the relationship between metabolism and weight control, the findings may pave the way for improved treatments for obesity and related weight issues.

Study Type

OBSERVATIONAL

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Group 1 (Lean): BMI 18.5-22.0 kg/m², reporting difficulty gaining weight * Group 2 (Obese): BMI \>30 kg/m², reporting difficulty losing weight * Healthy status as determined by medical history, physical examination, and laboratory tests * Stable weight (less than 5% fluctuation) over the past 6 months Exclusion Criteria: * Prediabetes (HbA1c \>5.6% or fasting blood glucose \>100 mg/dL) or diabetes mellitus * Conditions affecting appetite or energy expenditure (e.g., Cushing's syndrome, uncontrolled hyper-/hypothyroidism) * Gastrointestinal disorders that impact nutrient absorption (e.g., inflammatory bowel disease, malabsorption syndromes, ulcers) * Psychiatric conditions influencing eating behavior (e.g., active depression, anorexia nervosa, bulimia nervosa, borderline personality disorder) * Acute, unstable cardiovascular disease requiring hospitalization within the last 6 months (e.g., stent placement) * Cancer that required treatment in the past 5 years * Chronic kidney disease (Stage IV or higher, per NKF criteria) * Active infectious disease (e.g., HIV, hepatitis) * Current nicotine use or nicotine use within the last month prior to screening * Illicit drug use (e.g., amphetamines, cocaine, heroin, marijuana) * Regular high-intensity physical activity (≥1 hour/day) * Non-MRI-compatible metallic implants (e.g., artificial joints, metal plates) * Pregnancy or breastfeeding * Use of weight-loss medications * Clinically significant claustrophobia * Any other condition not mentioned above that, in the opinion of the investigator, could interfere with study participation or compromise patient safety

Outcomes

Primary Outcomes

Identification of Metabolic Phenotypes in Lean vs. Obese Individuals

We aim to determine whether individuals with obesity (BMI \>30 kg/m²) exhibit a more "thrifty" metabolic phenotype (lower resting metabolic rate \[RMR\] after 24-hour fasting and reduced diet-induced thermogenesis \[DIT\]) compared to lean individuals (BMI 18.5-22 kg/m²) who have trouble gaining weight, hypothesized to show a more "spendthrift" metabolic phenotype (increased RMR after fasting and higher DIT). RMR is measured via indirect calorimetry before and after a 24-hour fast, followed by a high-calorie, low-protein meal test to assess DIT.

Time frame: Measured at baseline (Day 1) and after 24-hour fasting (Day 2)

Secondary Outcomes

Correlation Between Fasting-Induced Energy Expenditure Changes and Diet-Induced Thermogenesis

Evaluate how the change in resting metabolic rate (RMR) after a 24-hour fast relates to diet-induced thermogenesis (DIT) following a high-calorie, low-protein meal. This will clarify the interaction between fasting adaptation and meal-related energy expenditure in lean vs. obese individuals.

Time frame: Baseline (Day 1), post-fasting (Day 2), and after the meal test (Day 2)

Assessment of Metabolic Flexibility via Respiratory Quotient

Determine whether individuals with obesity show a smaller shift in their respiratory quotient (RQ) after fasting and the meal test, indicating lower metabolic flexibility compared to lean participants.

Time frame: Baseline (Day 1), post-fasting (Day 2), and after the meal test (Day 2)

Correlation Between Weight Gain at 12-Month Follow-Up and Initial Metabolic Phenotype

Body weight (in kilograms) will be measured at baseline and again after 12 months using a calibrated scale. The correlation between weight change over this period and the initial metabolic phenotype (classified as "thrifty" or "spendthrift") will be assessed. The metabolic phenotype is determined by changes in resting metabolic rate (RMR) and diet-induced thermogenesis (DIT), both measured via indirect calorimetry.

Time frame: 12-month follow-up

Correlation Between Weight Gain at 12-Month Follow-Up and Diet-Induced Thermogenesis

Body weight (in kilograms) will be measured at baseline and again after 12 months using a calibrated scale. The correlation between weight change over this period and the magnitude of diet-induced thermogenesis (DIT) will be assessed. DIT is determined via indirect calorimetry after a controlled, low-protein meal. This assessment will help identify whether higher or lower DIT predicts long-term weight change.

Time frame: 12-month follow-up

Correlation Between Meal Test Diet-Induced Thermogenesis and Fibroblast Growth Factor 21 (FGF-21) Secretion

Fibroblast Growth Factor 21 (FGF-21) levels (in picograms per milliliter) will be measured in blood samples collected after the high-calorie, low-protein meal. The correlation between FGF-21 levels and diet-induced thermogenesis (DIT) will be assessed. DIT is measured using indirect calorimetry to quantify energy expenditure following the meal. This analysis will help determine whether FGF-21 may serve as a biomarker of metabolic adaptation.

Time frame: After the meal test (Day 2)

Correlation Between Gut Hormones and Changes in Energy Expenditure

Serum levels of gut hormones (e.g., ghrelin, glucagon-like peptide-1 \[GLP-1\]) will be measured in picograms per milliliter. Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) will be assessed via indirect calorimetry before and after a 24-hour fast, as well as after a high-calorie, low-protein meal. The correlation between gut hormone levels and changes in energy expenditure (RMR and DIT) will be evaluated to investigate hormonal influences on metabolic responses.

Time frame: Baseline (Day 1), after 24-hour fast (Day 2), and after the meal test (Day 2)

How Metabolism Affects Weight Loss and Gain

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts