Publications

Abstract

The notion that a defect in hypothalamic function may be a critical factor in the aetiology of obesity and diabetes stems from observations of the important role that this brain region plays in both the behavioural and metabolic events related to feeding and energy balance. Sensory events associated with the beginning of a meal trigger a series of metabolic changes, the function of which is to prepare an organism to receive, and properly dispose of, the incoming nutrients. Insulin release and nervous control of hepatic glucose output are important components of these neural, or cephalic-phase, sensory-driven metabolic events. The present review firstly summarizes evidence for direct autonomic nervous system links between the hypothalamus and the pancreas and liver, that is, the physical basis for cephalic-phase reflexes. Secondly, an assessment is made of both the normal function of the cephalic phase and how derangements might be central to the aetiology of important disease states such as obesity and non-insulin-dependent diabetes mellitus. A central hypothesis in this article is that a primary failure of normal cephalic-phase responses, over time, leads to increased post-meal hyperglycaemia and decreased thermogenesis. The persistent hyperglycaemia (among other metabolic abnormalities) leads to insulin resistance (insulin not being effective in disposing of glucose). The reduced post-meal thermogenesis leads to weight gain through reduced energy expenditure rather than through increased intake. The obesity in turn leads to further insulin resistance and, in genetically predisposed individuals, on to frank diabetes.