Exploring the Therapeutic Potential of Telmisartan Against High Fat Diet-Induced Nonalcoholic Fatty Liver Disease: A Dose- and Sex-Dependent Study in Mice
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a condition where excess fat builds up in the liver, often developing in response to poor diet consumption and associated metabolic disturbances (obesity, Type II diabetes). Telmisartan, an Angiotensin II receptor blocker commonly used for treating hypertension, may hold therapeutic value against the adverse metabolic effects of a high fat (HF) diet, including NAFLD. This project explores whether the effects of Telmisartan are dose- and sex-dependent in obese, prediabetic mice. Male and female C57BL/6J mice were fed high-fat (HF) or low-fat (LF) diet starting at ~3 months old; diet was maintained for the remainder of the study. After 3-4 months on the diet, HF mice were split into three groups and were given either water or a low (1 mg/kg) or high (5 mg/kg) dose of Telmisartan dissolved in drinking water. Mice on LF diet had only plain drinking water. Low-dose Telmisartan did not reduce blood pressure nor benefit metabolic outcomes. However, high-dose Telmisartan attenuated blood pressure, weight gain, and adiposity, with some benefits being sex-dependent. Additionally, high dose but not low dose Telmisartan reduced liver mass in HF diet-fed mice, potentially due to less fat buildup associated with NAFLD. Fixed livers are being stained with hematoxylin and eosin for assessment of steatosis (microvesicular fat), ballooning (macrovesicular fat) and leukocyte infiltration (inflammation), as well as Sirius Red staining for fibrosis, to determine the presence and severity of NAFLD. We hypothesize that high-dose Telmisartan will be more effective in treating mice with NAFLD attributable to chronic HF diet.
Faculty Sponsors
Dr. Lisa Robinson
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Exploring the Therapeutic Potential of Telmisartan Against High Fat Diet-Induced Nonalcoholic Fatty Liver Disease: A Dose- and Sex-Dependent Study in Mice
Alvin Sherman Library
Nonalcoholic fatty liver disease (NAFLD) is a condition where excess fat builds up in the liver, often developing in response to poor diet consumption and associated metabolic disturbances (obesity, Type II diabetes). Telmisartan, an Angiotensin II receptor blocker commonly used for treating hypertension, may hold therapeutic value against the adverse metabolic effects of a high fat (HF) diet, including NAFLD. This project explores whether the effects of Telmisartan are dose- and sex-dependent in obese, prediabetic mice. Male and female C57BL/6J mice were fed high-fat (HF) or low-fat (LF) diet starting at ~3 months old; diet was maintained for the remainder of the study. After 3-4 months on the diet, HF mice were split into three groups and were given either water or a low (1 mg/kg) or high (5 mg/kg) dose of Telmisartan dissolved in drinking water. Mice on LF diet had only plain drinking water. Low-dose Telmisartan did not reduce blood pressure nor benefit metabolic outcomes. However, high-dose Telmisartan attenuated blood pressure, weight gain, and adiposity, with some benefits being sex-dependent. Additionally, high dose but not low dose Telmisartan reduced liver mass in HF diet-fed mice, potentially due to less fat buildup associated with NAFLD. Fixed livers are being stained with hematoxylin and eosin for assessment of steatosis (microvesicular fat), ballooning (macrovesicular fat) and leukocyte infiltration (inflammation), as well as Sirius Red staining for fibrosis, to determine the presence and severity of NAFLD. We hypothesize that high-dose Telmisartan will be more effective in treating mice with NAFLD attributable to chronic HF diet.
