THE GUT-BRAIN BRAIN-GUT AXIS IN ANOREXIA - TOWARD AN UNDERSTANDING OFFOOD-INTAKE REGULATION

Our long-term objectives continue to be elucidation of the mechanisms that control spontaneous food intake (SFI), so that we may utilize thi s information in seeking ways to ameliorate abnormalities of SFI that occur in nutritionally ill humans. To this end, we have developed and used an Automated Computerized Rat Eater Meter (ACREM), which allows d etailed determinations of food intake and feeding patterns under a wid e variety of experimental conditions. Because food intake is the produ ct of meal number and meal size, these indexes were studied in a varie ty of experimental situations: normal male Fischer rats, genetically o bese Zucker rats, cancer-bearing rats, and an inflammatory bowel rat m odel. In each model, a reduction in food intake was accomplished; usua lly by a selective reduction in meal number and, occasionally, meal si ze; often in both. The independent regulation of meal number and meal size strongly suggests the existence of focal neuronal areas in the hy pothalamic food regulatory areas of the brain, which independently con trol these feeding indexes. To these feeding pattern studies were adde d in vivo focal hypothalamic microdialysis to correlate changes in mea l size and number with changes in the basic neurotransmitters, dopamin e and serotonin. To further gain an understanding of anorexia and food intake regulation in these models as it relates to the brain and gut interaction, we used metabolic stimulants, anatomic ablation, and elec trophysiological studies, cytokines, selective neurotransmitter agonis ts, and antagonists peripherally in Me gut and centrally in the brain. An integrated view of the gut-brain brain-gut control of food intake has emerged as a working and testable model system. The system include s oronasal pregastric factors, which stimulate an increase in LHA-dopa mine facilitating gastric compliance via efferent vagal fibers; postab sorptive factors, including nutrients and hepatoportal receptors via a fferent vagal fibers that inhibit further LHA-dopamine, thereby regula ting meal size. The same postabsorptive factors simultaneously decreas e VMH-dopamine, thereby determining postprandial intermeal duration, b ecause food intake is resumed when VMH-dopamine normalizes - thus regu lating meal number. Changes in plasma amino acids, the precursors for neurotransmitters, also affect brain availability for neurotransmitter s. This in particular applies to tryptophan, the precursor of serotoni n in the VMH, which induces a decrease in meal number and cytokines, w hich facilitate activity of both dopamine and serotonin.