In vivo expression of carbohydrate responsive element binding protein in lean and obese rats

ChREBP (Carbohydrate response element binding protein) is considered to mediate the stimulatory ChREBP (Carbohydrate response element binding protein) is considered to mediate the stimulatory effect of glucose on the expression of lipogenic genes. Its activity is stimulated by glucose. Less is known on the control of its expression. This expression could be controlled by nutritional (glucose, fatty acids) and hormonal (insulin) factors. We examined the in vivo nutritional control of ChREBP expression in liver and adipose tissue of Wistar rats. Compared respectively to the fed state and to a high carbohydrate diet, ChREBP mRNA concentrations were not modified by fasting or a high fat diet in rat liver and adipose tissue. FAS and ACC1 mRNA concentrations were on the contrary decreased as expected by fasting and high fat diets and these variations of FAS and ACC1 mRNA were positively related to those of SREBP-1c mRNA and protein, but not of ChREBP mRNA. Therefore i) ChREBP expression appears poorly responsive to modifications of nutritional condition, ii) modifications of the expression of ChREBP do not seem implicated in the physiological control of lipogenesis. To investigate the possible role of ChREBP in pathological situations we measured its mRNA concentrations in the liver and adipose tissue of obese Zucker rats. ChREBP expression was increased in the liver but not the adipose tissue of obese rats compared to their lean littermates. These results support a role of ChREBP in the development of hepatic steatosis and hypertriglyceridemia but not of obesity in this experimental model

Functional exploration of subcutaneous adipose stem cells in programming of metabolic disease

International audienc

A chronic exposure to a mixture of low-dosed food contaminants predisposes to the risk of developing metabolic disorders

International audienc

Contaminants alimentaires, obésité maternelle et statut métabolique de la descendance mâle et femelle, dans un modèle murin

National audienc

Dietary obesity in mice is associated with lipid deposition and metabolic shifts in the lungs sharing features with the liver

International audienceObesity is associated with both chronic and acute respiratory illnesses, such as asthma, chronic obstructive pulmonary disease (COPD) or increased susceptibility to infectious diseases. Anatomical but also systemic and local metabolic alterations are proposed contributors to the pathophysiology of lung diseases in the context of obesity. To bring perspective to this discussion, we used NMR to compare the obesity-associated metabolomic profiles of the lung with those of the liver, heart, skeletal muscles, kidneys, brain and serum from male C57Bl/6J mice fed with a high-fat and high-sucrose (HFHSD) diet vs. standard (SD) chow for 14 weeks. Our results showed that the lung was the second most affected organ after the liver, and that the two organs shared reduced one-carbon (1C) metabolism and increased lipid accumulation. Altered 1C metabolism was found in all organs and in the serum, but serine levels were increased only in the lung of HFHSD compared to SD. Lastly, tricarboxylic acid (TCA)-derived metabolites were specifically and oppositely regulated in the serum and kidneys but not in other organs. Collectively, our data highlighted that HFHSD induced specific metabolic changes in all organs, the lung being the second most affected organ, the main alterations affecting metabolite concentrations of the 1C pathway and, to a minor extend, TCA. The absolute metabolite quantification performed in this study reveals some metabolic specificities affecting both the liver and the lung, that may reveal common metabolic determinants to the ongoing pathological process

NMR Metabolomics Profiling Reveals Distinctive Signatures of an Obesogenic Diet in Mice: Uncovering Metabolite Signatures in Six Organs During a High-Fat, High-Sucrose Diet: A Cross-Sectional NMR Metabolomics Study

International audienceObesity is a significant risk factor for diseases like type 2 diabetes and cardiovascular disorders. Identifying biomarkers for early obesity-related disorders is crucial for precision medicine. We used NMR to analyze metabolomic profiles of key organs and serum in male C57Bl/6J mice fed a high-fat, high-sucrose diet (HFHSD, 36 % w/w fat, 16.6 % w/w sucrose, Envigo, France) or standard diet (STD, Rhod16A, Genobio) for 6, 10, and 14 weeks. Our study reveals organ-specific metabolite concentrations, highlighting age and diet effects and their interaction