Hypothalamic metabolic compartmentation during appetite regulation as revealed by magnetic resonance imaging and spectroscopy methods

Abstract

We review the role of neuroglial compartmentation and transcellular neurotransmitter cycling during hypothalamic appetite regulation as detected by Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) methods. We address first the neurochemical basis of neuroendocrine regulation in the hypothalamus and the orexigenic and anorexigenic feed-back loops that control appetite. Then we examine the main MRI and MRS strategies that have been used to investigate appetite regulation. Manganese-enhanced magnetic resonance imaging (MEMRI), Blood oxygenation level-dependent contrast (BOLD), and Diffusion-weighted magnetic resonance imaging (DWI) have revealed Mn2+ accumulations, augmented oxygen consumptions, and astrocytic swelling in the hypothalamus under fasting conditions, respectively. High field 1H magnetic resonance in vivo, showed increased hypothalamic myo-inositol concentrations as compared to other cerebral structures. 1H and 13C high resolution magic angle spinning (HRMAS) revealed increased neuroglial oxidative and glycolytic metabolism, as well as increased hypothalamic glutamatergic and GABAergic neurotransmissions under orexigenic stimulation. We propose here an integrative interpretation of all these findings suggesting that the neuroendocrine regulation of appetite is supported by important ionic and metabolic transcellular fluxes which begin at the tripartite orexigenic clefts and become extended spatially in the hypothalamus through astrocytic networks becoming eventually MRI and MRS detectable.

Glutamate and GABA in Appetite Regulation

“…Increased intracellular potassium ions concentrations trigger an osmotically driven, aquaporin 4 (AQP4)-mediated, water transport culminating with astrocytic swelling (60). By using diffusion weighting imaging, Lizarbe et al have recently shown significant increases in the slow diffusion parameters, consistent with astrocyte swelling response, in the hypothalamus of fasted relative to satiated animals (61, 62). On these grounds, we may hypothesize that, whereas an initial leptin-driven glutamate uptake in astrocytes shows anorexigenic potential (by diverting glutamate from neurons and thereby reducing glutamatergic neurotransmission), an excessive glutamate uptake by astrocytes, as occurs under orexigenic fasting conditions, causes astrocyte’s swelling and eventual response by amino release to the synaptic cleft (63) (augmenting glutamatergic neurotransmission associated with appetite enhancement).…”

Activation and Regulation of the Pattern Recognition Receptors in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance

“…The central nervous system (CNS) plays an important role to balance the energy equation by regulating energy intake and expenditures, in the context of the homeostatic regulation of body weight [6]. Insulin and leptin are transported from the circulation into the brain [30]. Signaling of these hormones in the hypothalamus inhibits food intake and increases energy expenditure.…”

Microstructural effects of Ramadan fasting on the brain: a diffusion tensor imaging study

“…The low ADC values of hypothalamus and insula could be secondary to a dysfunction similar to hypothalamic and insular inflammation. A recent study that was conducted with fasting mice and humans using advanced diffusion also suggested that changes in diffusion parameters could be associated with hypothalamic inflammation (20).…”