Role of brown fat and skeletal muscle in post-prandial clearance of triglycerides during and after cold exposure

Cardiovascular disease forms a major health problem in the Western world. An
important risk factor is hyperlipidemia, with elevated blood levels of
cholesterol and triglycerides. Earlier studies have shown that in both mice
(Khedoe PP et al, J Lip Res 2015) and in humans (Chondronikola M et al Cell
Metab 2016) that brown adipose tissue, when activated through cold, will
consume its intracellular lipid storage. The last mentioned study also showed
decreased plasma levels of triglycerides after cold exposure. The idea is that
brown adipose tissue, after combusting its own lipid storage, will take up
plasma fatty acids, presumably to replenish its intracellular storage.

With this study we hope to show that plasma triglyceride levels can be reduced
by cold exposure. We will study this by using meal tests during and after cold
exposure. These results will be correlated with measurements of brown fat
activity in these subjects, using a PET/CT scan.

1. To examine the effect of cold on post-prandial triglyceride metabolism using
a standardized meal test during and after cold exposure
2. To examine the relationship between cold-induced brown adipose tissue
activity and the changes in triglycerides during a standardized meal test. 3.
To examine the role of muscle tissue on cold-induced post-prandial triglyceride
metabolism.

The test subjects will undergo three meal tests, in which they will cosnume 2
high-fat milkshakes. The first meal test will take place under thermoneutral
conditions, the second meal test during cold exposure, and the third meal test
after cold exposure. On a seperate day, the presence and activity of brown
adipose tissue will be measured with a PET/CT scan.

Test subjects will be exposed to cold during the second and third meal test.
During this cold exposure the point of shivering is reached, to maximize the
non-shvering thermogenesis and stimulate brown adipose tissue activity.

The risks in this study are small, and the possible cosnequences af a small
impact.
After vena puncture or the placement of an intravenous cannula, a haematoma may
occur.
After the muscle biopsy, there is a risk of infection, bleeding, haematoma or
local nerve damage. Test subjects can experience a painful sensation at the
site of the biopsy for a couple of days.
During the PET/CT scan and the screening incidental findings could be made.

The amount of radiation is classified as low.

Further there is a considerable amount of time investment asked of subjects,
although test subjects are free to choose to participate in this study.