Biology subjects

do Rego, J.-L.

Publications and source records attributed to do Rego, J.-L..

4 recordsLinked to original sources

bioRxiv2026

Role of the gut microbiota in the remodelling of the jejunal, colonic, hepatic and blood proteomes in a mouse model of Anorexia Nervosa

Background: Anorexia nervosa (AN) is a typical form of eating disorder characterized by a severe body weight loss, a fear of gaining weight and dysmorphophobia. This disorder is associated with both psychiatric comorbidities and multi-organ dysfunctions. Increasing evidence suggests a role of the gut microbiota in the onset or maintenance of AN. Although a dysbiosis has been reported in patients with AN, the physiological consequences of this dysbiosis remain poorly documented. To gain further insight into the role of the gut microbiota in the pathophysiology of AN, we used the murine Activity-based Anorexia (ABA) model and compared the remodelling of the jejunal, colonic, hepatic and blood proteomes occurring in male mice with intact gut microbiota, as well as in gut microbiota-depleted animals. Results: We observed a significant proteome remodelling in several organs in response to the ABA model. More than 250 proteins involved in energy metabolism, catabolic processes, lipid metabolism, ghrelin regulation, and immune functions were found to show altered abundance in ABA mice compared to control mice. We observed in addition in the blood of ABA mice a significant increase in the level of circulating proteasome. By comparing mice treated or not with antibiotics, we identified 75 proteins whose regulation in ABA mice is gut-microbiota dependent. The other identified proteins were similarly affected in ABA mice with intact or depleted gut microbiota, suggesting that these factors are mainly regulated by food starvation and physical activity, and not directly by the gut microbiota. We finally confirmed that ORM2, a protein identified as significantly decreased in the plasma of ABA mice, is also decreased in the blood of patients suffering from AN. Conclusion: Our results demonstrate that the Activity-Based Anorexia model is associated with an extensive proteome remodelling in several organs and tissues. We highlight in addition that some of these targets are regulated in a gut microbiota-dependent manner, thereby reinforcing the hypothesis of a role of the gut microbiota in Anorexia Nervosa. Together, our study provides a valuable resource to better delineate the impact of undernutrition and maladaptive physical activity on the proteome of various organs and the role of the gut bacteria in the pathophysiology of Anorexia Nervosa.

pathology↗

bioRxiv2026

Chronic Activity-Based Anorexia triggers a glial response in the hippocampus independent of intestinal epithelial Toll-Like Receptor 4

Anorexia nervosa is characterized by maladaptive eating behavior and cognitive dysfunction, which could be explained by a neuroinflammation. A gut dysbiosis could link gastrointestinal alterations to central dysfunctions, particularly via the toll-like receptor 4 (TLR4), which has been shown to play a key role in the activity-based anorexia (ABA) model. We aimed to evaluate the neuroinflammation and its behavioral consequences in the ABA model, and to decipher the role of the microbiota-gut-brain axis, and more specifically of TLR4, in these alterations of the central nervous system. We show that chronic restriction is more strongly associated with gut inflammation, cecal microbiota alteration and neuroinflammatory processes in the hippocampus than acute restriction. The hippocampal glial response is characterized by a loss of astrocyte density, and an increased number of deramified microglia. We further demonstrate that these alterations are independent of TLR4 expressed by intestinal epithelial cells. In conclusion, our results highlight that the chronicity of ABA-associated undernutrition alters the response of glial cells in the hippocampus that is linked with changes in microbiota composition, highlighting the importance of faster diagnosis and treatment of AN.

neuroscience↗

bioRxiv2024

Gut microbiota regulates food intake in a rodent model of binge-eating disorder

ObjectiveBinge-eating disorder is characterized by recurrent episodes of consumption of large amounts of food within a short period of time, without compensatory behaviours. This disease is a major public health issue since it decreases patients quality of life and is associated with numerous comorbidities, encompassing anxiety, depression and complications associated with obesity. The pathophysiology of binge-eating disorder is complex and involves both endogenous, environmental and sociocultural factors. The gut microbiota has been proposed to be an important player in the onset or maintenance of eating disorders. Here, we aim to better delineate the potential role of the gut microbiota in binge-eating disorder. MethodWe used a model of binge-eating disorder where eight-weeks-old C57Bl/6 female mice had access during 2 hours, every 2 days over a 10-day period, to a highly palatable and high-calorie diet. Half of the animals received antibiotics to deplete their gut microbiota. Eating behaviour and other behavioural parameters were compared between groups. ResultsWe observed an increase in food intake in mouse exposed to high-fat high-sucrose diet, as well as tachyphagia and craving for food during binge-eating episodes. We demonstrate the gut microbiota depletion further increases food intake, specifically during binge-eating episodes. DiscussionThese results show that the gut microbiota is involved in the control of food intake during episodes of binge-eating. This strengthens the potential role of the gut bacteria in binge-eating disorder and open the way for future therapeutic strategies aiming at targeting patients gut microbiota.

animal behavior and cognition↗

bioRxiv2019

Glucose homeostasis is impaired in mice deficient for the neuropeptide 26RFa (QRFP)

Introduction26RFa (QRFP) is a biologically active peptide that has been found to control feeding behaviour by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism. Research design and methods26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro-26RFa was replaced by the iCre sequence. Energy and glucose metabolism was evaluated through measurement of complementary parameters. Morphological and physiological alterations of the pancreatic islets were also investigated. ResultsOur data do not reveal significant alteration of energy metabolism in the 26RFa-deficient mice except the occurrence of an increased basal metabolic rate. By contrast, 26RFa mutant mice exhibit an altered glycemic phenotype with an increased hyperglycemia after a glucose challenge associated with an impaired insulin production, and an elevated hepatic glucose production. 2D and 3D immunohistochemical experiments indicate that the insulin content of pancreatic {beta} cells is much lower in the 26RFa-/- mice as compared to the wild-type littermates. ConclusionDisruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis with, in particular, a deficit in insulin production by the pancreatic islets. These findings further support the notion that 26RFa is an important regulator of glucose homeostasis. Significance of this studyO_ST_ABSWhat is already known about this subject?C_ST_ABS26RFa is a biologically active peptide produced in abundance in the gut and the pancreas. 26RFa has been found to regulate glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. What are the new findings?Disruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis with, in particular, a deficit in insulin production by the pancreatic islets, assessing therefore the notion that 26RFa is an important regulator of glucose homeostasis. How might these results change the focus of research or clinical practice?Identification of a novel actor in the regulation of glucose homeostasis is crucial to better understand the general control of glucose metabolism in physiological and pathophysiological conditions, and opens new fields of investigation to develop innovative drugs to treat diabetes mellitus.

physiology↗