The Role of the Human Hypothalamus in Food Intake Networks: An MRI Perspective

Hypothalamus (HT), this small structure often perceived through the prism of neuroimaging as morphologically and functionally homogeneous, plays a key role in the primitive act of feeding. The current paper aims at reviewing the contribution of magnetic resonance imaging (MRI) in the study of the role of the HT in food intake regulation. It focuses on the different MRI techniques that have been used to describe structurally and functionally the Human HT. The latest advances in HT parcellation as well as perspectives in this field are presented. The value of MRI in the study of eating disorders such as anorexia nervosa (AN) and obesity are also highlighted.

Cholecystokinin system is involved in the anorexigenic effect of peripherally applied palmitoylated prolactin-releasing peptide in fasted mice

Prolactin-releasing peptide (PrRP) has been proposed to mediate the central satiating effects of cholecystokinin (CCK) through the vagal CCK1 receptor. PrRP acts as an endogenous ligand of G protein-coupled receptor 10 (GPR10), which is expressed at the highest levels in brain areas related to food intake regulation, e.g., the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS). The NTS and PVN are also significantly activated after peripheral CCK administration. The aim of this study was to determine whether the endogenous PrRP neuronal system in the brain is involved in the central anorexigenic effect of the peripherally administered CCK agonist JMV236 or the CCK1 antagonist devazepide and whether the CCK system is involved in the central anorexigenic effect of the peripherally applied lipidized PrRP analog palm-PrRP31 in fasted lean mice. The effect of devazepide and JMV236 on the anorexigenic effects of palm-PrRP31 as well as devazepide combined with JMV236 and palm-PrRP31 on food intake and Fos cell activation in the PVN and caudal NTS was examined. Our results suggest that the anorexigenic effect of JMV236 is accompanied by activation of PrRP neurons of the NTS in a CCK1 receptor-dependent manner. Moreover, while the anorexigenic effect of palm-PrRP31 was not affected by JMV236, it was partially attenuated by devazepide in fasted mice. The present findings indicate that the exogenously influenced CCK system may be involved in the central anorexigenic effect of peripherally applied palm-PrRP31, which possibly indicates some interaction between the CCK and PrRP neuronal systems.

Role of the G protein-coupled receptors GPR84 and GPR119 in the central regulation of food intake in rainbow trout

We evaluated the role of GPR84 and GPR119 in food intake regulation in fish using rainbow trout (Oncorhynchus mykiss) as a model. In a first experiment, we assessed the effects on food intake of intracerebroventricular treatment with agonists of these receptors. In a second experiment, we assessed in hypothalamus and hindbrain the impact of the same treatments on mRNA abundance of neuropeptides involved in the metabolic control of food intake (npy, agrp1, pomca1, and cartpt) as well as in changes in parameters related to signalling pathways and transcription factors involved in the integrative response leading to neuropeptide production. Treatment with both agonists elicited an anorectic response in rainbow trout attributable to changes observed in the mRNA abundance of the four neuropeptides. Changes in neuropeptides relate to changes observed in mRNA abundance and phosphorylation status of the transcription factor Foxo1. These changes occurred in parallel with changes in phosphorylation status of Ampkα and Akt, mRNA abundance of mTOR as well as in signalling pathways related to PLCβ and IP3. These results allow us to suggest that 1) at least part of the capacity of fish brain to sense MCFA like octanoate depends on the function of GPR84, and 2) the capacity of fish brain to sense NAE or triglyceride-derived molecules through binding of these ligands to GPR119.

Urinary Dopamine Excretion Rate Decreases during Acute Dietary Protein Deprivation and Is Associated with Increased Plasma Pancreatic Polypeptide Concentration

Background: Dopamine, a key neurotransmitter in the autonomic nervous system participating in the homeostatic balance between sympathetic and parasympathetic divisions, is involved in food intake regulation. Objective: We investigated whether dopamine is altered by acute fasting or overfeeding diets with varying macronutrient content. Design: Ninety-nine healthy subjects underwent 24-h dietary interventions including eucaloric feeding, fasting, and five different overfeeding diets in a crossover design. Overfeeding diets (200% of eucaloric requirements) included one diet with 3%-protein (low-protein high-fat overfeeding—LPF: 46%-fat), three diets with 20%-protein, and a diet with 30%-protein (44%-fat). Urine was collected for 24 h and urinary dopamine concentration was quantified by high-performance liquid chromatography. Plasma pancreatic polypeptide (PP) concentration, an indirect marker of parasympathetic activity, was measured prior to and after each diet after an overnight fast. Results: During 24-h of fasting, dopamine decreased on average by ~14% compared to eucaloric conditions, whereas PP increased by two-fold (both p < 0.001). Lower dopamine during 24-h fasting correlated with increased PP (r = −0.40, p < 0.001). Similarly, on average urinary dopamine decreased during LPF by 14% (p < 0.001) and lower dopamine correlated with increased PP (r = −0.31, p = 0.01). No changes in dopamine and PP concentrations were observed during other overfeeding diets (all p > 0.05). Conclusions: Dopamine concentrations decrease during short-term fasting and overfeeding with a low-protein diet. As both dietary conditions have in common protein deficit, the correlation between dopamine and PP suggests a compensatory mechanism underlying the shift from sympathetic to parasympathetic drive during dietary protein deprivation.

Functional Fine-Tuning of Metabolic Pathways by the Endocannabinoid System—Implications for Health and Disease

The endocannabinoid system (ECS) employs a huge network of molecules (receptors, ligands, and enzymatic machinery molecules) whose interactions with other cellular networks have still not been fully elucidated. Endogenous cannabinoids are molecules with the primary function of control of multiple metabolic pathways. Maintenance of tissue and cellular homeostasis by functional fine-tuning of essential metabolic pathways is one of the key characteristics of the ECS. It is implicated in a variety of physiological and pathological states and an attractive pharmacological target yet to reach its full potential. This review will focus on the involvement of ECS in glucose and lipid metabolism, food intake regulation, immune homeostasis, respiratory health, inflammation, cancer and other physiological and pathological states will be substantiated using freely available data from open-access databases, experimental data and literature review. Future directions should envision capturing its diversity and exploiting pharmacological options beyond the classical ECS suspects (exogenous cannabinoids and cannabinoid receptor monomers) as signaling through cannabinoid receptor heteromers offers new possibilities for different biochemical outcomes in the cell.