Functional magnetic resonance imaging of human hypothalamic responses to glucose, fructose, sucrose, and sucralose.

Obesity is becoming an increasingly prevalent problem. A cause of obesity is
aberrant feeding behavior. Taste of food plays an important role in the
palatability of food and the hedonic benefits in consuming them. The
hypothalamus is a subcortical structure that plays a key role in the intricate
and complex neuroendocrine interactions that govern food intake and energy
homeostasis. Using functional magnetic resonance imaging (fMRI) we have
previously measured the hypothalamic function during nutrient ingestion. In
healthy humans, an oral glucose load decreases hypothalamic neuronal activity,
whereas no such response was observed in patients with type 2 diabetes and a
delayed and attenuated response in obese participants. This indicates that in
these patients, the hypothalamus inappropriately perceives and/or processes
signals in response to a nutrient load, possibly reflecting an abnormal
perception of the current metabolic status. In most foods, however, taste is
being enhanced not by glucose but by sucrose and fructose (HFCS flavourings -
high fructose corn syrup), which are much cheaper additives. From dietary point
of view, the hypothalamic responses of these specific sugars are unclear.
Glucose is a monosaccharide and rapidly taken up in the blood and metabolized
throughout the entire body. Our previous data even have shown that that the
administration of glucose results in a hypothalamic response that is much
faster than is expected based on an pure abdominal pathways. Fructose has a
sweetness that is a little higher than glucose, is also a monosaccharide, but
can only be metabolized in the liver. From food/obesity homeostatic point of
view, we do not expect that fructose induces a decrease in hypothalamic
neuronal activity, and will therefore not be involved in hypothalamic
response/decisions *to eat or not to eat*. Sucrose, better known as table sugar
is a disaccharide composed of the monosaccharides glucose and fructose. This
disaccharide is broken down in the stomach into separate glucose and fructose
monosacchrides by the enzyme sucrose. Sucrose has a similar sweetness compared
with glucose and fructose. We expect that the hypothalamic response of sucrose
is less than glucose based on molecular weight and the previous effects of
hypothalamic BOLD response dose dependency, and will occur later since the
disaccharide has to be broken down first. For control conditions we will use
plain water (no taste / no calories) and sucralose, which is a non-caloric
sweetener. Our overall hypothesis is that glucose demonstrates the fastest and
deepest hypothalamic response, followed by sucrose. The effects of fructose and
sucralose will be much less but may have a Pavlov effect on the hypothalamus,
based on its sweet taste. The water condition is the absolute *0* and reference
in all these studies.

Primary objective of the exploratory study is to assess whether the BOLD signal
intensity of the hypothalamus differs between the different sugars and
sweeteners of glucose, fructose, sucrose and sucralose.

The study design is a randomized cross-over observational study in healthy male
volunteers.

The study will consist of five occasions. There will be an interval of at least
one week between the occasions. On all occasions, the subject will be admitted
to the Clinical Research Unit of the LUMC. After anthropometric measurements
(weight), fMRI to monitor hypothalamic activity will be performed after an
ingestion of 1 of the following stimuli; water at room temperature, glucose (50
gram dissolved in 300 ml water), fructose (50 gram dissolved in 300 ml water),
sucrose (50 gram dissolved in 300 ml water), or sucralose (0.1g; matched for
sweetness with sucrose, dissolved in 300 ml water). Water will be plain tap
water and non-chlorinated. The order of conditions will be randomly assigned to
the subjects. The hypothalamus will be continuously imaged for 20 minutes using
a conventional T2*-weighted gradient-echo pulse sequence.
Before and after the MRI 5ml of blood will be drawn and subjects will be asked
to give psycophysical ratings of hunger, taste and sweetness.