Adipogenic capacity as a mediator of weight gain

A major problem in the treatment of obesity is the weight regain after weight
reduction. It has been shown that a genetic component plays a role in this,
since some people have a predisposition towards weight gain in comparison to
others. This genetic background is still unclear, although some polymorphisms
are found to be associated with obesity and weight gain. This genetic component
influences various other factors en could have an effect on energy expenditure,
adipogenic capacity and physical activity.

This study investigates the differences in response between people with a
low/high/medium predisposition towards weight regain (based on their genetic
background) to a period of weight reduction followed by weight maintenance in
terms of energy expenditure, body composition, adipogenic capacity, physical
acitivity and hormone levels.

In this study subjects will be assigned to three groups, each with a high, low
or medium predisposition for weight gain. This will be based on the FTO allele,
with AA, TT and AT respectively (p.17 van het research protocol). These groups
will all follow a weight loss period of 2 months followed by a weight
maintenance period of 10 months. During this year subjects have to visit the
university 6 times (see p. 13+14):

1. screening
2. start weight loss (0)
3. half-way weight loss (1maand)
4. end weight loss (2 maanden)
5. first part weight maintenance (5 maanden)
6. end weight maintenance (12 maanden)

De duration of these test days depends on the group, like described earlier (E2
of p13 + 14 of the research protocol).

The diet (modifast) is an intervention of this study. The subjects will follow
this diet for 2 months and it consists of 2.1MJ/day as 3 meal subsituting
shakes or puddings with fruit en vegetables to get the vitamines.

all subjects:
- blood sampling at screening, before diet, after diet, after weight
maintenance (risks of minor bruising and pain)
- diet (Modifast)
- completing questionnaires
- measuring weigth, height, waist and hip
- deuterium, urine collection and bodpod measurements
- wearing TracmorD
subjects in group with high/low predisposition:
- fat biopsy (risks of minor bruising and pain)
- stay in respiration chamber overnight
- ventilated hood measurements
- doubly labeld water and urine collection

All subjects visit the university six times. The time burden for each subject
depends on whether they belong to the high or low predisposition group or not.
For all subjects there is a screening of around 45 minutes. Four visits for the
group with only limited measurements (body weight, waist and hip circumference
and body composition) will take 60 minutes and one visit of 20 minutes. In
total these subjects need to stay at the university for approximately 305
minutes (=5h). Three visits for the subjects in the groups with a high/low
predisposition for weight regain will take one night and the subsequent
morning, so approximately 16h. The other two visits will be 20 and 60 minutes.
In total these subjects need to stay at the university for approximately 50h.
There are no risks for the subjects in consuming the VLED (Modifast, together
with the recommended fruit and vegetables) as the macronutrient composition and
vitamins/minerals content meet the Dutch recommended daily allowance. This VLED
will demand some energy from the subjects at home. However, losing weight is a
great advantage for these subjects, so probably they have enough will-power to
complete these 2 months VLED. There is a risk of minor bruising during blood
sampling. Deuterium is an isotope of water that naturally appears in the body.
Drinking it does not expose the subject to any risks. The doubly labelled water
is safe to use in humans since the water is labelled with stable isotopes. The
concentrations of the samples are with an enrichment of 100 to 200 ppm far
below 10000 ppm or 1%, where effects on biological systems have been observed.
Collection of urine at home is only a minor time burden for the subjects.
Studies in the respiratory chamber will be conducted using standard operating
procedures. A pair of subjects will always participate in the study at the same
time and therefore they will never be alone. The subjects will be able to
contact the investigators during the entire night. In addition, they will be
able to get out of the chamber at any time they feel uncomfortable. Taking a
fat biopsy will be done under local anaesthetic, which only gives a very brief
tingling pain at the site of infiltration under the skin. Local anaesthesia
occurs with most standard clinical procedures in which this is used, resulting
in minimal risks. Allergies for local anaesthetics will be one of the exclusion
criteria. The biopsy itself can give a mild soreness and bruising near the
biopsy site. Minimal scarring rarely occurs. Wearing the Tracmor will not have
any risk or burden.