Endocrinol Metab.  2024 Aug;39(4):559-568. 10.3803/EnM.2024.2025.

Regulation of Energy and Glucose Homeostasis by the Nucleus of the Solitary Tract and the Area Postrema

• Bruce K
• Garrido AN
• Zhang SY
• Lam TK

• KMID: 2558938
• DOI: http://doi.org/10.3803/EnM.2024.2025

Abstract

The central nervous system regulates feeding, weight and glucose homeostasis in rodents and humans, but the site-specific mechanisms remain unclear. The dorsal vagal complex in the brainstem that contains the nucleus of the solitary tract (NTS) and area postrema (AP) emerges as a regulatory center that impacts energy and glucose balance by monitoring hormonal and nutrient changes. However, the specific mechanistic metabolic roles of the NTS and AP remain elusive. This mini-review highlights methods to study their distinct roles and recent findings on their metabolic differences and similarities of growth differentiation factor 15 (GDF15) action and glucose sensing in the NTS and AP. In summary, future research aims to characterize hormonal and glucose sensing mechanisms in the AP and/or NTS carries potential to unveil novel targets that lower weight and glucose levels in obesity and diabetes.

Keyword

Area postrema; Solitary nucleus; GDF15; Glucose; Feeding; Energy metabolism; Glucose metabolism; Stereotaxic surgery

Figure

• 

  Fig. 1. Surgical targeting and metabolic impacts of the area postrema (AP) and nucleus of the solitary tract (NTS). (A) Schematic of rat skull and brain anatomy to provide reference for NTS and AP stereotaxic surgery (top). Images show coronal sections of the rat brain with the AP and NTS highlighted, with corresponding surgical coordinates (bottom). (B) Schematic detailing the specific metabolic effects of growth differentiation factor 15 (GDF15) and glucose sensing in the AP and NTS. In the AP, GDF15’s feeding and weight-lowering effects partly stem from the GDNF family receptor α-like (Gfral)-calcitonin gene-related peptide (CGRP) pathway. These effects may not be dependent on glucagon-like peptide-1 receptor (Glp1r) activation, despite the co-expression of Glp1r with Gfral in AP cells. GDF15-Gfral axis in the AP enhances glucose tolerance and insulin sensitivity and inhibits hepatic glucose production as well. Lastly, Gfral-expressing cells in the AP and leptin receptor (Lepr)-expressing cells in the NTS synergistically reduce feeding and weight. In the NTS, Glp1r and Lepr activation lower feeding and weight. With respect to glucose sensing, both the NTS and AP share a glucose transporter 1 (GLUT1) and pyruvate kinase-dependent glucose sensing mechanism that regulates peripheral glucose metabolism. Images adapted from BioRender. PBN, parabrachial nucleus; PDH, pyruvate dehydrogenase; DCA, dichloroacetate; HFD, high-fat diet.

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