Biology subjects

Foppen, E.

Publications and source records attributed to Foppen, E..

6 recordsLinked to original sources

bioRxiv2024

Limited microglial metabolic improvement with time-restricted feeding in diet-induced obesity

Time-restricted eating has shown promise for improving metabolic health in obese humans via incompletely resolved mechanisms. In this study, we investigated how time-restricted feeding (TRF) at different times of the day affects microglial immunometabolism using Wistar rats. We found that in high-fat diet (HFD)-fed obese rats, TRF during the active phase reduced fat mass, altered rhythmicity of the microglial transcriptome, and prevented an increase in hypothalamic microglia. These effects were dampened or absent with TRF during the resting phase. However, a HFD-induced microglial immunometabolic phenotype, characterized by reduced electron transport chain and increased lipid metabolism gene expression, and metabolic inflexibility, was not reversed by TRF in either the active or resting phase, indicating that reprogrammed microglial metabolism in obesity is a persistent cellular functional change that requires further study.

immunology↗

bioRxiv2023

A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We demonstrate that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an 2-adrenergic receptor agonist, highlighting the functional implication of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. These findings identify a novel top-down neural mechanism engaged by OB GLP-1 signaling to control insulin secretion via the SNS.

physiology↗

bioRxiv2023

Dual role of striatal astrocytes in behavioral flexibility and metabolism in the context of obesity

Brain circuits involved in metabolic control and reward-associated behaviors are potent drivers of feeding behavior and are both dramatically altered in obesity, a multifactorial disease resulting from genetic and environmental factors. In both mice and human, exposure to calorie-dense food has been associated with increased astrocyte reactivity and pro-inflammatory response in the brain. Although our understanding of how astrocytes regulate brain circuits has recently flourish, whether and how striatal astrocytes contribute in regulating food-related behaviors and whole-body metabolism is still unknown. In this study, we show that exposure to enriched food leads to profound changes in neuronal activity and synchrony. Chemogenetic manipulation of astrocytes activity in the dorsal striatum was sufficient to restore the cognitive defect in flexible behaviors induced by obesity, while manipulation of astrocyte in the nucleus accumbens led to acute change in whole-body substrate utilization and energy expenditure. Altogether, this work reveals a yet unappreciated role for striatal astrocyte as a direct operator of reward-driven behavior and metabolic control.

physiology↗

bioRxiv2022

The addiction-susceptibility TaqIA/Ankyrin repeat and kinase domain containing 1 kinase (ANKK1) controls reward and metabolism through dopamine receptor type 2 (DR2)-expressing neurons

Significant evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the Taq1A polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the Ankyrin repeat and kinase domain containing 1 kinase (ANKK1) near the dopamine D2 dopamine receptor (DR2) gene. Depending on race it affects 30 to 80% of the population and its homozygous expression of the A1 allele correlates with a 30 to 40% reduction of striatal DR2, a typical feature of addiction, over-eating and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior is unknown. Here we used transgenic and viral-mediated strategies to reveal the role of ANKK1 in the regulation of activity and functions of the striatum. We found that Ankk1 is preferentially enriched in striatal DR2 expressing neurons and that Ankk1 loss-of-function in dorsal and ventral striatum leads to alteration in learning, impulsive, and flexible behaviors resembling the endophenotypes described in A1 carriers. We also observed an unsuspected role of ANKK1 in striatal DR2-expressing neurons in the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with versus without the A1 allele. Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for ANKK1 in the regulation of body metabolism.

neuroscience↗

bioRxiv2022

Hypothalamic astrocyte control systemic glucose metabolism and energy balance via regulation of extra-synaptic glutamate signaling

The hypothalamus is key in the control of energy balance. However, to this day strategies targeting hypothalamic neurons failed to provide viable option to treat most metabolic diseases. Conversely, the role of astrocytes in systemic metabolic control has remained largely unexplored. Here we show that obesity promotes anatomically restricted remodeling of hypothalamic astrocyte activity. In the paraventricular nucleus (PVN) of the hypothalamus, chemogenetic manipulation of astrocytes results in bidirectional control of neighboring neuron activity, autonomic outflow, glucose metabolism and energy balance. Such process recruits a mechanism involving the astrocytic control of ambient glutamate levels, which becomes defective in obesity. Positive or negative chemogenetic manipulation of PVN astrocyte Ca2+ signals respectively worsen or improves metabolic status of diet-induced obese mice. Collectively, these findings highlight a yet unappreciated role for astrocyte in the direct control of systemic metabolism and suggest potential targets for anti-obesity strategy.

physiology↗

bioRxiv2020

Identification of an endocannabinoid gut-brain vagal mechanism controlling food reward and energy homeostasis

The regulation of food intake, a sine qua non requirement for survival, thoroughly shapes feeding and energy balance by integrating both homeostatic and hedonic values of food. Unfortunately, the widespread access to palatable food has led to the development of feeding habits that are independent from metabolic needs. Among these, binge eating (BE) is characterized by uncontrolled voracious eating. While reward deficit seems to be a major contributor of BE, the physiological and molecular underpinnings of BE establishment remain elusive. Here, we combined a physiologically relevant BE mouse model with multiscale in vivo approaches to explore the functional connection between the gut-brain axis and the reward and homeostatic brain structures. Our results show that BE elicits compensatory adaptations requiring the gut-to-brain axis which, through the vagus nerve, relies on the permissive actions of peripheral endocannabinoids (eCBs) signaling. Selective inhibition of peripheral CB1 receptors resulted in a vagus-dependent increased hypothalamic activity, modified metabolic efficiency, and dampened activity of mesolimbic dopamine circuit, altogether leading to the suppression of palatable eating. We provide compelling evidence for a yet unappreciated physiological integrative mechanism by which variations of peripheral eCBs control the activity of the vagus nerve, thereby in turn gating the additive responses of both homeostatic and hedonic brain circuits which govern homeostatic and reward-driven feeding. In conclusion, we reveal that vagus-mediated eCBs/CB1R functions represent an interesting and innovative target to modulate energy balance and counteract food-reward disorders.

neuroscience↗