Abdominal Obesity, Liver Fat
Conditions
Keywords
Metabolic health, Phenotyping, Abdominal obesity, Abdominal adiposity, Liver fat, Belly fat
Brief summary
In the Belly Fat study, the effects of two different caloric-restricted diets on metabolic health will be examined in male and female subjects with increased abdominal adiposity (BMI \>27 kg/m2). Metabolic health is defined as health of the primary metabolic organs the liver, gut and the adipose tissue, examined in a static state as well as after the application of a challenge test. The diets are equally caloric-restricted, but differ in nutrient composition. It is hypothesized that one of the two diets causes a larger improvement in organ health and reduction in liver fat.
Detailed description
Rationale: It is known that in particular visceral fat (abdominal obesity) and fat deposition in non-adipose tissue such as the liver are important factors related to metabolic health, such as the degree of insulin resistance, dyslipidaemia and other well-established cardio-metabolic risk factors. The arise of pathological consequences of abdominal obesity are a result of a disturbance in the elegant interplay between metabolic organs, such as the liver, adipose tissue and gut. Several nutrients have demonstrated to exert positive or negative effects on the health and functioning of metabolic organs. A diet (whole dietary approach) can thus be a power tool to improve the health status of individuals with abdominal obesity by improving organ health. Objective: The primary objective of this study is to compare the effects of two different diets on the static metabolic health status as assessed by determination of organ health and, more specifically, of lipid accumulation in the liver. The application of a mixed meal challenge test will be used to gain insight in the dynamic metabolic health status. A secondary objective is to determine the reaction (brain activity) of individuals with abdominal obesity after visual and olfactory food-cues. Study design and intervention: Randomized, parallel design consisting of three groups: 1. 40 subjects, 12-wk nutritional intervention based on dietary advice: diet with 30% caloric restriction and a Western style nutrient composition 2. 40 subjects, 12-wk nutritional intervention based on dietary advice: diet with 30% caloric restriction with a nutrient composition aimed at improving organ health and reducing liver fat 3. 30 subjects, control group, no nutritional intervention (optional: dietary advice at the end of the study period) Measurements on metabolic health will be conducted at baseline and after 12-wk intervention and include: * MR imaging for determining body fat distribution * MR spectroscopy for quantification of liver fat * Blood sampling (plasma and PBMCs) before and several timepoints after mixed meal challenge * Adipose tissue sampling before and after mixed meal challenge * Vascular measurements before and after mixed meal challenge * Urine and feces sampling Study population: Males and females, 40-70 yrs old, BMI \> 27 kg/m2
Interventions
Dietary advice, guided by professional dieticians. Caloric restricted (-30en%) diet with Western type nutrient composition (SFA, carbohydrates, sugars, fruit juice, meat, dairy)
Dietary advice, guided by professional dieticians. Caloric restricted (-30en%) diet with nutrient composition aiming at an improvement in organ health and a reduction in liver fat (PUFA, fish, soy protein, whole grain)
Sponsors
Study design
Eligibility
Inclusion criteria
* Age 40-70y at the time of recruitment * BMI \>27kg/m2 or waist circumference \>102cm (males) or \>88cm (females)
Exclusion criteria
* Diabetic (normoglycemic according to WHO criteria (OGTT, fasting blood glucose\< 7 mmol/L, after 2 hr \<11.1 mmol/L) * Daily intake of alcohol of \>30g (men) or \>20g (women) * Tobacco smoker * Abuse of drugs * Any medical conditions or (metal) devices interfering with or posing a risk for the participant in 1H-MRS/MRI scanning (e.g. claustrophobia, pace maker, surgical screws/pins, artificial joints or heart valves, etc.) * Diagnosed with any long-term medical condition (i.e. cardiovascular disease, gastrointestinal disease, renal dysfunction) * Use of medications known to interfere with glucose or lipid homeostasis (i.e. corticosteroids) * Allergic to fish oil or unwilling to consume fish oil supplements * Unwilling to comply with dietary guidelines * Restricted to a vegetarian dietary regime
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vascular functions (blood pressure and arterial stiffness) before and after mixed meal challenge | Baseline and after 12-wk intervention | PWA |
| Intrahepatic lipid accumulation (IHL) | Baseline and after 12-wk intervention | Assessment of IHL by means of 1H-MRS (magnetic resonance spectroscopy) |
| Body fat distribution | Baseline and after 12-wk intervention | Assessment of body fat distribution (SAT/VAT) by means of MRI (magnetic resonance imaging) |
| Adipose tissue gene expression before and 4h after a mixed meal challenge | Baseline and after 12-wk intervention | Micro-array/qPCR |
| Markers of liver health (plasma) before and after mixed meal challenge | Baseline and after 12-wk intervention | Liver enzymes |
| Cardio-metabolic risk factors (plasma) before and after mixed meal challenge | Baseline and after 12-wk intervention | Insulin, glucose, Tg |
| Inflammatory markers (plasma) before and after mixed meal challenge | Baseline and after 12-wk intervention | Cytokines |
| Markers of adipose tissue health (plasma) | Baseline and after 12-wk intervention | Adipokines |
| Markers of gut health (plasma) | Baseline and after 12-wk intervention | Gut hormones |
| Microbiota (faeces) | Baseline and after 12-wk intervention | — |
| Urinary metabolites | Baseline and after 12-wk intervention | — |
| PBMC gene expression profile | Baseline and after 12-wk intervention | Micro-array/qPCR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Satiety and wellbeing before and after mixed meal challenge | Baseline and after 12-wk intervention | Assessment by validated questionnaires |