Effects of β-carotene supplementation on adipose tissue thermogenic capacity in ferrets ( Mustela putorius furo)

Abstract

We previously described that the intake of pharmacological doses of beta-carotene (BC) resulted in higher body weight gain in the ferret (Mustela putorius furo), an animal model that resembles human subjects in terms of intestinal BC absorption and metabolism. These results were some way unexpected considering the condition of BC as a vitamin A precursor and the previous data in rodents showing these compounds as thermogenic activators. Here, we aimed to characterise in the ferret whether the mentioned changes in body weight could be explained by changes in adipose tissue thermogenic capacity. We studied the effects of 6-month supplementation with BC (0.8 and 3.2 mg/kg per d) on adipose tissue morphology and uncoupling protein-1 (UCP1) content. BC supplementation resulted in higher body weight (the high dose), induced depot- and dose-dependent hypertrophy of white adipocytes, decreased the amount of brown-like multilocular adipocytes in the retroperitoneal depot and decreased UCP1 content in different fat depots. To ascertain whether BC effects could be mediated by retinoic acid (RA), 1 week supplementation with RA (0.25 and 25 mg/kg per d) was also studied. RA treatment resulted in a slight decrease in adiposity, decreased cell lipid accumulation and increased UCP1 content, suggesting that the effects of BC on thermogenic capacity are not through RA. In conclusion, RA, but not BC, may have in the ferret comparable effects with those described in rodents, whereas differences concerning BC and RA treatments may be attributable to the different BC metabolism in the present animal model with a lower conversion of BC to RA compared with rodents.