Angiotensin II type 2 receptor mediates high fat diet-induced cardiomyocyte hypertrophy and hypercholesterolemia

Area of Science:

• Cardiovascular Science
• Metabolic Disorders
• Molecular Biology

Background:

• Obesity is a primary risk factor for cardiovascular and metabolic diseases.
• Previous research indicated Angiotensin II type 2 receptor (AT2R) deletion protects against high-fat (HF) diet-induced metabolic issues.
• The specific role of AT2R in obesity-related cardiac hypertrophy is not well understood.

Purpose of the Study:

• To investigate the role of AT2R in cardiac hypertrophy and remodeling associated with obesity.
• To determine if AT2R deletion impacts metabolic changes and cardiac structure in mice fed a high-fat diet.

Main Methods:

• Male AT2R knockout (AT2RKO) and wild-type (AT2RWT) mice were subjected to a control or high-fat (HF) diet for 10 weeks.
• Cardiac AT2R expression was measured.
• Body weight, glucose tolerance, fat mass, cholesterol levels, and cardiac remodeling were assessed.
• In vitro experiments used pharmacological inhibition and knockdown of AT2R to assess leptin-induced cardiomyocyte hypertrophy.

Main Results:

• HF diet increased cardiac AT2R expression in obese mice.
• AT2R deletion did not alter body weight gain, glucose intolerance, or fat mass gain.
• However, AT2R deficiency prevented HF diet-induced hypercholesterolemia and cardiac remodeling.
• In vitro, AT2R inhibition or knockdown blocked leptin-induced cardiomyocyte hypertrophy.

Conclusions:

• AT2R is implicated in the cardiac hypertrophy and remodeling resulting from obesity.
• Targeting AT2R may offer a therapeutic strategy for managing obesity-related cardiac complications.