Abstract
A high-fat diet gives rise to metabolic syndrome, a cluster of risk factors for developing obesity, type II diabetes, hypertension, and dyslipidemia resulting in cardiovascular disease. Overactivation of the brain renin-angiotensin system (b-RAS), mainly through the angiotensin II type 1 receptor (AT1R), causes vasoconstriction and neuroinflammation, thereby increasing the likelihood of neurodegenerative disorders. Telmisartan, an angiotensin receptor blocker (ARB) that is selective for the AT1R type, typically used to treat hypertension, can also reduce weight gain, while improving dyslipidemia and glucose metabolism in male mice fed a high-fat diet. However, whether telmisartan can reverse behavioral changes caused by a high-fat diet is unknown. This study assesses the effects of treatment with telmisartan on metabolic outcomes and cognitive-behavioral function in high-fat diet fed mice. Male and female mice were provided a low-fat or high-fat diet from 3-9 months of age. A subset of mice on the high-fat diet were treated with a low (1 mg/kg/day) or high (5 mg/kg/day) telmisartan dosage during the last two months of their high-fat diet. Treatment with high dose telmisartan significantly decreased body weight and systolic blood pressure in male and female mice fed a high-fat diet. Behavior tests showed sex and dose-dependent differences, with high-fat male mice having improved cognitive performance with the 5 mg/kg/day dose of telmisartan. In contrast, high-fat females cognitive performance improved with the 1 mg/kg/day dose. In vitro receptor autoradiography is currently being performed to assess the effects of a high-fat diet and ARB treatment on b-RAS AT1R expression.
We acknowledge NIH, grant # 1T34GM145509 for partial support of this research.
Faculty Sponsors
Dr. Robert C. Speth, Dr. Lisa Robinson
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-2-2025 12:30 PM
End Date
4-3-2025 12:00 AM
The Therapeutic Potential of Telmisartan on Male and Female Mice Subjected to a High Fat Diet
Alvin Sherman Library
A high-fat diet gives rise to metabolic syndrome, a cluster of risk factors for developing obesity, type II diabetes, hypertension, and dyslipidemia resulting in cardiovascular disease. Overactivation of the brain renin-angiotensin system (b-RAS), mainly through the angiotensin II type 1 receptor (AT1R), causes vasoconstriction and neuroinflammation, thereby increasing the likelihood of neurodegenerative disorders. Telmisartan, an angiotensin receptor blocker (ARB) that is selective for the AT1R type, typically used to treat hypertension, can also reduce weight gain, while improving dyslipidemia and glucose metabolism in male mice fed a high-fat diet. However, whether telmisartan can reverse behavioral changes caused by a high-fat diet is unknown. This study assesses the effects of treatment with telmisartan on metabolic outcomes and cognitive-behavioral function in high-fat diet fed mice. Male and female mice were provided a low-fat or high-fat diet from 3-9 months of age. A subset of mice on the high-fat diet were treated with a low (1 mg/kg/day) or high (5 mg/kg/day) telmisartan dosage during the last two months of their high-fat diet. Treatment with high dose telmisartan significantly decreased body weight and systolic blood pressure in male and female mice fed a high-fat diet. Behavior tests showed sex and dose-dependent differences, with high-fat male mice having improved cognitive performance with the 5 mg/kg/day dose of telmisartan. In contrast, high-fat females cognitive performance improved with the 1 mg/kg/day dose. In vitro receptor autoradiography is currently being performed to assess the effects of a high-fat diet and ARB treatment on b-RAS AT1R expression.
We acknowledge NIH, grant # 1T34GM145509 for partial support of this research.
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