The Belly Fat Study: Nutritional Intervention to Improve Metabolic Health in Subjects With Increased Abdominal Adiposity

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.

Study Overview

• Status: Completed
• Conditions: Liver Fat; Abdominal Obesity
• Intervention / Treatment: Other: Dietary advice, Targeted; Other: Dietary advice, Western

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

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No dietary advice; No dietary intervention
Experimental: Dietary advice, Targeted; 12-wk dietary advice	Other: Dietary advice, Targeted; 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)
Experimental: Dietary advice, Western; 12-wk dietary advice	Other: Dietary advice, Western; Dietary advice, guided by professional dieticians. Caloric restricted (-30en%) diet with Western type nutrient composition (SFA, carbohydrates, sugars, fruit juice, meat, dairy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrahepatic lipid accumulation (IHL)	Assessment of IHL by means of 1H-MRS (magnetic resonance spectroscopy)	Baseline and after 12-wk intervention
Body fat distribution	Assessment of body fat distribution (SAT/VAT) by means of MRI (magnetic resonance imaging)	Baseline and after 12-wk intervention
Adipose tissue gene expression before and 4h after a mixed meal challenge	Micro-array/qPCR	Baseline and after 12-wk intervention
Markers of liver health (plasma) before and after mixed meal challenge	Liver enzymes	Baseline and after 12-wk intervention
Cardio-metabolic risk factors (plasma) before and after mixed meal challenge	Insulin, glucose, Tg	Baseline and after 12-wk intervention
Inflammatory markers (plasma) before and after mixed meal challenge	Cytokines	Baseline and after 12-wk intervention
Markers of adipose tissue health (plasma)	Adipokines	Baseline and after 12-wk intervention
Markers of gut health (plasma)	Gut hormones	Baseline and after 12-wk intervention
Microbiota (faeces)		Baseline and after 12-wk intervention
Urinary metabolites		Baseline and after 12-wk intervention
PBMC gene expression profile	Micro-array/qPCR	Baseline and after 12-wk intervention
Vascular functions (blood pressure and arterial stiffness) before and after mixed meal challenge	PWA	Baseline and after 12-wk intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satiety and wellbeing before and after mixed meal challenge	Assessment by validated questionnaires	Baseline and after 12-wk intervention

Collaborators and Investigators

• Sponsor: Wageningen University
• Investigators: Principal Investigator: L Afman, PhD, Wageningen University. Department Human Nutrition. Nutrition, Metabolism & Genomics Group

Publications and helpful links

General Publications

• Schutte S, Esser D, Siebelink E, Michielsen CJR, Daanje M, Matualatupauw JC, Boshuizen HC, Mensink M, Afman LA; Wageningen Belly Fat Study team. Diverging metabolic effects of 2 energy-restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity. Am J Clin Nutr. 2022 Jul 6;116(1):132-150. doi: 10.1093/ajcn/nqac025.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: July 16, 2014
• First Submitted That Met QC Criteria: July 16, 2014
• First Posted (Estimate): July 18, 2014

Study Record Updates

• Last Update Posted (Estimate): April 17, 2015
• Last Update Submitted That Met QC Criteria: April 16, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Phenotyping; Metabolic health; Abdominal adiposity; Abdominal obesity; Liver fat; Belly fat
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Abdominal
• Other Study ID Numbers: NL44614.081.13