16Objectives: To investigate the early cardiometabolic abnormalities along with WAT and BAT 17 remodeling in short-term fructose feeding mice model. Methods: Mice (n=10-11/group) were fed 18 for four weeks with control diet (AIN93-M) or experimental diets rich in glucose or fructose. We 19 investigated body weight, body adiposity, blood glucose, lipid and hepatic parameters, and white 20 (WAT) and brown adipose tissue (BAT) histopathology. Results: Fructose feeding promoted 21 neither weight gain nor hypertrophy of visceral and subcutaneous WAT depots, but the fat was 22 redistributed toward visceral depots. Glucose, lipid and hepatic metabolic dysfunction were not yet 23 noticed in fructose-fed mice, with the exception for an elevation in total cholesterol and hepatic 24 weight without steatosis. BAT mass did not increase, and it was proportionally reduced compared 25 with visceral WAT in fructose feed mice. BAT suffered premature adverse morphological 26 remodeling, characterized by increased lipid deposition per tissue area in enlarged intracellular lipid 27 droplets. Conclusion: Short-term fructose feeding redistributes body fat, changes the proportion of 28 BAT to visceral fat, and promotes BAT adverse remodeling, characterized by enlarged intracellular 29 lipid droplets. 30

Introduction: Animal models are used to test the safety and efficacy of drugs. They are often administered to rodents in the drinking water, but it has some limitations, such as the drug stability, variations of water consumption and body mass. We investigated telmisartan (TEL) stability in mice drinking water by UV spectrophotometry, and if water intake and body mass fluctuations change drug ingestion.Methods: Female C57BL/6 mice at two months old, were fed for eight weeks with a purified AIN93M diet, or a high-fat high-sucrose diet (HFHS). TEL 5 mg/Kg/day was administered ad libitum to mice in the drinking water during three weeks concomitant with diets, summing 11 weeks of diet feeding. Results: UV spectrophotometry could detect TEL at the wavelength of 300 nm, and it remained stable in mice drinking water for seven days, at the concentration expected. Mice gain weight after eight weeks on high-fat high-sucrose diet feeding, and TEL 5 mg/kg/day in the drinking water for three weeks reduced it. TEL did not change water intake. Not adjusting TEL concentration weekly would lead to a higher intake of TEL by mice. Discussion:We demonstrated that body mass and water intake fluctuations significantly change the amount of drug that the animal receive, and it would add a bias to the experiment. TEL remains stable for at least seven days in wrapped mice water bottles in the animal care facility, and UV spectrophotometry proved to be a simple and low-cost method to detect TEL in mice drinking water.