Biology subjects

Vily-Petit, J.

Publications and source records attributed to Vily-Petit, J..

3 recordsLinked to original sources

bioRxiv2026

Contributions of the gut microbiota and intestinal gluconeogenesis to metabolic adaptations in a mouse model of anorexia nervosa.

Anorexia nervosa is a metabolic-psychiatric disorder characterized by severe food restriction, often accompanied by hyperactivity, associated with high mortality and the lack of specific pharmacological treatment. Despite a marked energy deficit, patients paradoxically maintain euglycemia, suggesting adaptations in energy homeostasis. This study aims to characterize the interactions between food restriction, the gut microbiota and peripheral organs in a mouse model mimicking anorexia nervosa. Our results show that food-restricted mice exhibit improved glucose tolerance and increased expression of the gluconeogenic genes G6pc and Pck1 in the intestine, suggesting an adaptation in endogenous glucose production. Gut microbiota analysis reveals a marked shift in composition in food-restricted mice, with an increase in the Lachnospiraceae and Marinifilaceae families and a decrease in Lactobacillaceae. These changes are associated with metabolic parameters such as glycemia, body weight, and GLP-1 levels. Transfer of microbiota from food-restricted mice into control mice improves glucose tolerance and increases the gluconeogenic gene expression. Furthermore, the improvement in glucose tolerance is abolished in mice lacking intestinal gluconeogenesis, suggesting that intestinal gluconeogenesis is required for the effects of the FR microbiota on glucose homeostasis. Overall, these findings highlight a complex metabolic adaptation in a mouse model of anorexia nervosa, involving interactions between the gut microbiota, intestinal gluconeogenesis and maintenance of energy homeostasis.

physiology↗

bioRxiv2021

Intestinal Gluconeogenesis Regulates Brown and White Adipose Tissues Functions in mice

ObjectiveIntestinal gluconeogenesis, via the initiation of a gut-brain nervous circuit, accounts for the metabolic benefits linked to dietary proteins or fermentable fibre in rodents and has been positively correlated with the rapid amelioration of body weight after gastric bypass surgery in obese humans. In particular, the activation of intestinal gluconeogenesis moderates the development of hepatic steatosis accompanying obesity. In this study, we investigated the specific effects of intestinal gluconeogenesis on adipose tissue metabolism, independently of its induction by nutritional manipulation. MethodsWe used two transgenic mouse models of suppression or overexpression of G6PC, the catalytic subunit of glucose-6 phosphatase, the key enzyme of endogenous glucose production, specifically in the intestine. ResultsUnder a hypercaloric diet, mice with a genetic overexpression of intestinal gluconeogenesis showed a lower adiposity and higher thermogenic capacities than wild-type mice, featuring marked browning of white adipose tissue and prevention of the whitening of brown adipose tissue. Suppression of sympathetic nervous signalling in brown adipose tissue impairs the activation of thermogenesis. Conversely, mice with genetic suppression of intestinal gluconeogenesis exhibit an increase in adiposity under standard diet, associated with a decreased expression of markers of thermogenesis in both the brown and white adipose tissues. ConclusionIntestinal gluconeogenesis is sufficient in itself to activate the sympathetic nervous system and prevent the expansion and the metabolic alterations of brown and white adipose tissues metabolism under high calorie diet, thus preventing the development of obesity. These data increase knowledge of the mechanisms of weight reduction in gastric bypass surgery and pave the way of new approaches to prevent or cure obesity.

physiology↗

bioRxiv2019

Atrial natriuretic peptide orchestrates a coordinated physiological response to fuel non shivering thermogenesis

Atrial natriuretic peptide (ANP) is a cardiac hormone controlling blood volume and arterial pressure in mammals. It is unclear whether and how ANP controls cold-induced thermogenesis in vivo. Here we show that acute cold exposure induces cardiac ANP secretion in mice and humans. Genetic inactivation of ANP promotes cold intolerance and suppresses about half of cold-induced brown adipose tissue (BAT) activation in mice. While white adipocytes are resistant to ANP-mediated lipolysis at thermoneutral temperature in mice, cold exposure renders white adipocytes fully responsive to ANP to activate lipolysis and a thermogenic program, a physiological response which is dramatically suppressed in ANP null mice. ANP deficiency also blunts liver triglycerides and glycogen metabolism thus impairing fuel availability for BAT thermogenesis. ANP directly increases mitochondrial uncoupling and thermogenic genes expression in human white and brown adipocytes. Together, these results indicate that ANP is a major physiological trigger of BAT thermogenesis upon cold exposure in mammals.

physiology↗