Neuro-hormonal integration of metabolism: challenges and opportunities in the postgenomic era.

Humans are multicellular organisms designed to provide continuous nutrition to all constituent cells by means of nutrient homeostasis through genomicnutrient-metabolic interaction. This process is highly regulated and integrated through neuro-hormonal control processes at various levels of organization. Metabolism at the cellular level is primarily regulated by cell-signaling pathways and substrate environments for specific metabolic events. This is achieved through the regulation of futile substrate cycles within the cell by substrates and signal-sensitive gene expressions. Metabolism at the intercellular level is primarily regulated by paracrine, autocrine, hormones, and other neurotransmitters that alter the functional state of metabolic networks within individual cells and the cell-to-cell relationship. At the organism’s physiological level, metabolic regulation is achieved through complex neuro-endocrine circuitry, and its integration with nutritional signals that translate these interrelationships into nutrients and energy homeostasis [1]. Over the last century, tremendous progress has been made at the physiological level in the following areas: feeding behavior; major function of the digestive processes in the gut and gut-brain-endocrine axis; hypothalamic and autonomic pathways and neurotransmitters in regulating hunger, satiety, and energy metabolism; endocrine control of metabolic function of organs involved in energy homeostasis (brain, gut, liver, muscle, and adipose tissue), and altered metabolic pathways and/or control system failure that can lead to diseases such as obesity, metabolic syndrome, diabetes mellitus, cancer, and other disorders. This has been the subject of various recent workshops sponsored by Nestlé [2–5]. Allison SP, Go VLW (eds): Metabolic Issues of Clinical Nutrition. Nestlé Nutrition Workshop Series Clinical & Performance Program, vol 9, pp 227–242, Nestec Ltd., Vevey/S. Karger AG, Basel, © 2004.