Endocrine Abstracts

Many feeding hormones that are produced by peripheral tissues depend in part or whole on their abilities to cross the blood–brain barrier (BBB) in order to access their CNS sites of action. Some of these hormones, such as leptin, are transported across the BBB by saturable transport systems. A hallmark of BBB saturable transport systems for regulatory substances is that they are themselves modulated by pathophysiological events. Leptin transport, for example, is decreased in obesity and starvation and increased by epinephrine administration. Inhibition of leptin transport across the BBB is the cause of ‘peripheral resistance’ to leptin in obesity. Why leptin transport is inhibited in both starvation and obesity and why an anorectic should be excluded from its site of action during obesity are partially answered by the observation that serum triglycerides also inhibit leptin transport. Hypertriglyceridemia occurs in both starvation and obesity and so can explain at least in part why leptin transport is inhibited in these conditions. To the extent it can be assumed that starvation was a much more common event during evolution than obesity, it can be assumed that starvation played the dominant role in the evolution of leptin–triglyceride phenomenon. Thus, triglyceridemia may have evolved as a signal to the BBB of starvation, not obesity, and thus explain why it limits brain access of an anorectic. Triglycerides and epinephrine also affect the BBB transport of insulin and ghrelin; however, they show variations on the leptin pattern. Besides anorexia, leptin also has effects on reproduction and neural development which are mediated through the CNS. Triglycerides also affects cognition, impairing learning, memory, and LTP. These effects appear to be mediated by triglycerides within the CNS and raise the possibility that triglycerides cross the BBB and may affect leptin receptor function within the CNS.