The effect of diet interventions on hypothalamic nutrient sensing pathways in rodents

• The hypothalamus plays a fundamental role in regulating energy homeostasis
• Glucose and fatty acids serve as signaling factors to control energy balance
• Diets can affect the nutrient sensing pathways in different ways
• A free-choice high fat high-sucrose (fcHFHS) diet increases hypothalamic gene expression

The hypothalamus plays a fundamental role in regulating homeostatic processes including regulation of food intake. Food intake is driven in part by energy balance, which is sensed by specific brain structures through signaling molecules such as nutrients and hormones. Both circulating glucose and fatty acids decrease food intake via a central mechanism involving the hypothalamus and brain stem. Besides playing a role in signaling energy status, glucose and fatty acids serve as fuel for neurons. This review focuses on the effects of glucose and fatty acids on hypothalamic pathways involved in regulation of energy metabolism as well as on the role of the family of peroxisome proliferator activated receptors (PPARs) which are implicated in regulation of central energy homeostasis. We further discuss the effects of different hypercaloric diets on these pathways.