Fatty acid sensing in the gut and the hypothalamus: In vivo and in vitro perspectives

The ability to properly sense both ingested and circulating nutrients is crucial for the maintenance of metabolic homeostasis. As such, both the gastrointestinal tract and the hypothalamus have demonstrated the capacity to sense and effectively respond to nutrients, such as fatty acids, to control food intake and glucose production to regulate energy and glucose homeostasis. In modern, Westernized societies, obesity and diabetes rates continue to rise unabated, due in part to an increase in highly palatable high-fat diet consumption. Thus, our understanding in the ability of the body to successfully monitor lipids is more vital than ever. This review details the current understanding of both the gut and the brain, specifically the hypothalamus, in sensing fatty acids. Highlighting both in vivo and in vitro studies, we explore some of the mechanisms upon which different fatty acids activate enteroendocrine and neural lipid-sensing signaling mechanisms to subsequently lower food intake and glucose production to ultimately regulate metabolic homeostasis. A better understanding of these lipid-sensing pathways could lay the groundwork for successful pharmacological targets for the treatment of obesity and diabetes.