Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding

Abstract

The essential role of the brain in maintaining energy homeostasis has motivated the drive to define the neural circuitry that integrates external and internal stimuli to enact appropriate and consequential metabolic and behavioral responses. The hypothalamus has received significant attention in this regard given its ability to influence feeding behavior, yet organisms rely on a much broader diversity and distribution of neuronal networks to regulate both energy intake and expenditure. Because energy balance is a fundamental determinant of survival and success of an organism, it is not surprising that emerging data connect circuits controlling feeding and energy balance with higher brain functions and degenerative processes. In this review, we will highlight both classically defined and emerging aspects of brain control of energy homeostasis.

Hypothalamic Lipids: Key Regulators of Whole Body Energy Balance

“…The hypothalamus regulates energy balance through the integration of peripheral signals and generates an appropriate output that modulates food intake and energy metabolism [4][5][6] . Similar to other tissues, the hypothalamus is able to synthetize and utilize lipids to its own function, and may therefore suffer from lipid alterations comparable to those in peripheral organs that lead to metabolic damage [97,99] ( Fig.…”

“…pability to respond with appropriate outputs such as regulation of the intensity of hunger and subsequently food seeking behaviour, modulation of the degree of energy expenditure (including basal metabolism, physical activity, and thermogenesis), and nutrient partitioning, as well as control of reproduction and growth [6][7][8][9][10][11][12][13] .…”

Gut-Brain Cross-Talk in Metabolic Control

“…Another potent orexigenic peptide, neuropeptide Y (NPY), is co-expressed with AGRP. AGRP/NPY neurons project directly to POMC neurons and upon stimulation inhibit POMC firing through inhibitory Y1 and GABA receptors among likely multiple other levels of intercellular communication (reviewed in Waterson and Horvath, 2015). …”

Control of sleep by a network of cell cycle genes

“…Both PL and PI regions are proposed to be analogous to the mammalian hypothalamus, 41 a major sleep and feeding center. 42,43 It may be that an unidentified subpopulation of the hypothalamic neurons function in a manner analogous to PL neurons to integrate sleep and metabolic signals.…”