Metabolic phenotyping of individuals with abdominal obesity and high levels of hepatic fat before and after dietary interventions

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, muscle and gut. These organs interact with each other
via signaling molecules and metabolites. An imbalance in the secretion of these
substances may lead to impaired functioning and health of these organs.

Determination of the health of these organs can be accomplished by, in
particular, by subjecting these organs to a challenge meal (for instance a high
fat or sugar load) to measure how the body and the specific organs are able to
cope with this stressor. By examining these organs in a more dynamic state, one
can gain more insight in the metabolic flexibility of these organs.

Lifestyle, in particular dietary habits, plays an important role in abdominal
obesity and the health of metabolic organs, especially the liver. 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.

The objective of the Belly Fat project is to accurately determine the personal
health status of individuals with higher levels of abdominal fat (belly fat)
and hepatic fat. This so-called phenotyping is essential to allow intervening
with dietary and life style changes before the onset of disease.

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.

The Belly Fat Study is an intervention study in which subjects with high levels
of abdominal fat and a higher intrahepatic lipid (IHL) accumulation are
extensively phenotyped before and after receiving dietary advice which is
deployed as a tool to induce weight loss and to improve organ health.

Allocation to one of the two designed dietary advices, counselling by
professional dieticians.
Both diets are based on a caloric restriction of 30%.

(1) Dietary advice based on a more Western dietary pattern: 30E% fats
(saturated and unsaturated), 15E% protein (animal and vegetable sources),
50-55E% carbohydrates (complex carbohydrates and simple carbohydrates e.g. the
monosaccharide fructose).
(2) Dietary advice based on a combination of nutrients of which we expect
(based on scientific literature) that it will cause a larger improvement in
organ health and reduction in liver fat when compared to the standard diet:
30-35E% fats (mono- and poly unsaturated fatty acids, ~1400mg n-3 fatty acids),
20-25E% protein (mainly vegetable sources, mainly soy) and 40-45% carbohydrates
(low glycaemic index, complex carbohydrates, low in fructose).

Furthermore, a control group is added in which participants do not receive any
form of intervention.

- Subjects that will participate in the study will invest a total of 23-27
hours.
- The dietary advice is prepared by qualified dieticians, hence it does not
pose the participants at any risk for deficiencies or excessive consumption of
certain nutrients.
- Participants in the control group are offered dietary counselling (including
a recipe book) and the end of the study periode, hence they will also profit
frorm health benifits.
- (f)MRI/MRS is a non-invasive and safe procedure as long as no
contraindication is met (metal devices such as aneurysm clips, neural
stimulators, pacemakers/defibrillators, cochlear implant etc.).
- The physical fitness test may cause some physical discomfort, such as muscle
aches, irregular heartbeat, cramping or an abnormal blood pressure. To minimize
these risks, subjects will be monitored throughout the whole test in terms of
heart rate, blood pressure and O2 consumption. The test will be discontinued in
case abnormalities are detected.
- The Hb value of each participants will be determined before participation,
individuals cannot participate in the study if this value is below 8.4 mml/L.
Blood collection will therefore not lead to anaemia.
- Adipose tissue and muscle biopsies can occasionally cause a local hematoma or
bruise and some participants may report pain or discomfort.
- Fructose will be supplied to participants in the standard group in the form
of normal food products such as fruit juice, hence the risk of habituation is
minimal.