Effects of triglycerides, obesity, and starvation on ghrelin transport across the blood–brain barrier

Abstract

Human ghrelin is transported across the blood-brain barrier (BBB) of normal mice. Here, we studied the effects of triglycerides, obesity, and starvation in retired breeder mice maintained on a high fat diet, mice age-matched to the retired breeders but maintained on normal chow, and 8 week old mice maintained on breeder chow. The rate of ghrelin transport across the BBB was studied by both the intravenous administration method of multiple-time regression analysis and by the brain perfusion method. We found: 1) obese, aged mice lost the ability to transport intravenously administered ghrelin across the BBB, resulting in an inverse relation between body weight and ghrelin BBB permeability; 2) serum triglycerides promoted transport of intravenously administered ghrelin across the BBB, whereas epinephrine had no effect; 3) fasting tended to promote ghrelin transport across the BBB as most readily shown in brain perfusion studies; 4) evidence suggested that a serum factor promoted ghrelin transport in 8 week old mice. Overall, these results show that serum factors and physiological states influence the rate at which ghrelin is transported across the blood-brain barrier.