Glucose metabolism, diet composition, and the brain

Excessive intake of saturated fat and sugar contributes to both obesity and diabetes development. Since intake of fat and sugar-sweetened beverages exceeds recommended levels worldwide, it is essential to: 1) Understand how fat and sugar intake affect glucose metabolism, and 2) Expand the knowledge on peripheral glucose control, especially regarding its central regulation. In part 1, we used a unique animal model based on free choice & access to saturated fat and/or sugar water, previously shown to induce clear hyperphagic snacking behaviour, obesity and glucose intolerance. We showed that short-term hypercaloric fat intake induced hepatic-, while the combined intake of fat and sugar induced peripheral insulin resistance. Furthermore, long-term feeding of both components impaired the early phase glucose-induced insulin response, which was associated with impaired β cell innervation. Excessive intake of saturated fat and sugar results not only in obesity, but also in unique functional changes in the striatum, a brain area classically known to regulate reward but not known to control peripheral glucose concentrations. In part 2, we discovered an unexpected role for the striatum, and especially the nucleus accumbens shell (sNAc), in the control of glucose metabolism, in which the neurotransmitters dopamine and serotonin in the sNAc exerted opposite effects on glucose metabolism. Increasing dopamine inhibited hypothalamic function, which in turn decreased hepatic glucose production. These novel findings suggest a sNAc-hypothalamus-liver-axis involved in glucose control. Together, these studies provided better understanding of how fat/sugar consumption affects glucose metabolism, and novel insights in the central regulation of glucose metabolism.