Background

Cholesterol facilitates membrane fluidity and is a precursor for steroid hormones, bile acids and vitamin D. Animals are provided with cholesterol either from the diet or by de novo synthesis. Surplus of cholesterol may be harmful as its accumulation in blood vessel walls can cause atherosclerosis. It has been shown that the activation of brown adipose tissue (BAT) by cold reduces hypercholesterolemia (Berbee et al., 2015). It was, however, unclear whether BAT activity alters acute peripheral dietary cholesterol handling. To address this question, we orally administered mice with recombinant triglyceride-rich lipoprotein particles (rTRL) labeled with [4-¹⁴C]-Cholesterol and measured the organ distribution of the radiolabel 4 h after gavage. The biodistribution of radiolabeled cholesterol in vivo has been measured before (Szigeti et al., 1972; Townsend et al., 2001). However, in these studies, the radioactive cholesterol was either supplied by the diet or injected intravenously. Furthermore, other studies have assessed the fractional cholesterol absorption rate over a longer period of time (48 and 72 h) (Zilversmit and Hughes, 1974; Turley et al., 1994), As we were especially interested in the plasma clearance and the cholesterol uptake into the BAT after cold exposure, we chose to analyze the organs after a rather short period of time (4 h). Instead of applying an oil gavage, we used rTRL since the oil gavage resembles a rather unphysiologic condition (very high amount of lipids) but not a postprandial situation. Additionally, supplying the tracer with the diet is not suitable in cold-treated mice as they eat twice as much as when kept at warm ambient temperatures (30 °C).