An accelerated mouse model for atherosclerosis and adipose tissue inflammation

Area of Science:

• Cardiovascular Science
• Metabolic Science
• Inflammation Research

Background:

• Obesity and metabolic syndrome are major risks for type 2 diabetes and cardiovascular disease.
• Obesity-associated adipose tissue inflammation is a common cause of these conditions.
• A suitable animal model for studying these co-occurring conditions is lacking.

Purpose of the Study:

• To establish and characterize a murine model for studying diet-induced obesity, adipose tissue inflammation, metabolic disorders, and atherosclerosis simultaneously.
• To compare the effects of high-fat, high-cholesterol diets with and without high sucrose on cardio-metabolic disease development.

Main Methods:

• LDL receptor-deficient (LDLR-/-) mice were fed either a high-fat, high-cholesterol (HFC) diet or a high-fat, high-sucrose, high-cholesterol (HFSC) diet for 12-20 weeks.
• Assessed parameters included obesity, adipose tissue inflammation, insulin resistance, glucose tolerance, hepatic lipid accumulation, and atherosclerotic lesion formation.

Main Results:

• Both HFC and HFSC diets induced obesity, adipose tissue inflammation, insulin resistance, and impaired glucose tolerance in LDLR-/- mice.
• The HFSC diet significantly accelerated adipose tissue inflammation and atherosclerotic lesion development compared to the HFC diet at 12-16 weeks.
• No significant differences were observed between diets after 20 weeks of feeding.

Conclusions:

• High sucrose content in high-fat diets accelerates obesity-driven metabolic complications and atherosclerosis in LDLR-/- mice.
• This LDLR-/- mouse model fed a high-fat, high-sucrose, cholesterol-enriched diet is a suitable and time-saving model for cardio-metabolic diseases.
• Results support the link between adipose tissue inflammation and atherosclerotic plaque formation.