Role of the Histone Acetyltransferases p300/CBP in Brown Adipose Tissue Adaptive Thermogenesis

Obesity is rising in Canada at an alarming rate, which is bad for our healthcare system because it results in diseases like heart attacks and diabetes. Although eating less and exercising more can reduce weight, these lifestyle changes can be difficult to maintain, prompting interest in finding ways to ramp up the calorie-burning processes in the body to promote weight loss. Brown adipose tissue (BAT) is a kind of fat that is found in both humans and mice. Unlike white adipose tissue, BAT is specialized for calorie burning rather than storage. We don't know exactly how the body controls how much BAT it makes, how it turns BAT on for burning energy to control body weight, or why some people lose their BAT with age.

One possible way these processes might be controlled is via proteins that 'open' and 'close' DNA within BAT to turn key calorie-burning genes on and off. Proteins that close DNA within BAT can worsen obesity by blocking BAT development, so the body can't burn as many calories. We are interested in how proteins that 'open' DNA (specifically, a pair called p300 and CBP) in BAT can influence energy expenditure.

To find out whether p300/CBP activate BAT calorie burning, we will induce obesity in mice that have p300/CBP working within their BAT, and in mice without these proteins. We expect mice missing p300/CBP will also have problems making BAT, so they will also be unable to burn energy using this tissue – resulting in the development of obesity and diabetes.