Hypothalamic Nutrient Sensing and Energy Balance

Abstract

Hypothalamic neurons have the capacity to sense and alter their activity in response to fluctuations in local nutrient concentrations. Alterations in glucose, fatty acid and amino acid concentrations have all been demonstrated to affect neuronal excitability and/or intracellular signaling pathways. The degree to which such changes in nutrient availability have the capacity to modify energy balance varies across nutrient type. The underlying mechanisms through which various nutrients affect food intake and overall energy balance involve both specific and shared neuronal substrates.

Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism

“…4,8,10 In addition to isolated central signals, peripheral hormone and nutrient signals also have significant roles in informing the central control centers regarding the metabolic state of peripheral tissues. 4,8,10 Although previous research has pointed to the roles of numerous nutrients in controlling hypothalamic signaling, the current studies focused on the documented effects of FA on food intake regulation. 17,18,22,24,34 Our data support an important role for central FA, specifically in the hypothalamus, in the regulation of food intake and body weight.…”

“…Central nervous system fuel sensing, especially in the hypothalamus, is thought to be significantly involved in energy homeostasis both centrally and peripherally. 8,10 Both central administration of OA 17 and systemic OA-based lipid infusions 36 have been shown to inhibit hepatic glucose production and support glucose homeostasis through hypothalamic lipid sensing. We measured serum glucose, TAGs, FFA and b-hydroxybutyrate concentrations to gain insight into the effects of central FA administration along with induced changes in food intake and body weight on peripheral metabolism.…”

“…1,2,6,7 Nutrient sensing within the hypothalamus has a critical role in the complex network of signals controlling energy metabolism. [8][9][10] In addition to hormonal signals, nutrients crossing the blood-brain barrier, such as glucose and lipids, affect central control of food intake and energy expenditure. 8,9 Despite a brain preference for glucose as its primary energy source, more recent evidence suggests that hypothalamic lipid metabolism and signaling have significant roles in regulating energy balance, food intake and the etiology of metabolic diseases.…”

Overview of the Physiological Control of Eating

“…Also, glucose availability influences the expression and turnover of several catabolic and anabolic neuropeptides [103] which presumably mediate the effects of glucose-sensing on eating. These hypothalamic circuits are discussed in detail in the chapter by Moran [86].…”

“…This suggests that fluctuations in the availability or utilization of energy-yielding substrates -mainly glucose and fatty acids -or a common denominator of their utilization, control eating. Sensing of fuel availability or utilization leading to altered eating occurs in both the periphery and the brain [85,86] (fig. 6).…”