Summary
On a high fat diet, obese SM/J mice initially develop metabolic dysfunction, including impaired glucose tolerance and elevated fasting glucose. These abnormalities resolve spontaneously by 30 weeks of age despite persistence of obesity. The mice dramatically expand their brown adipose depots as they resolve glycemic dysfunction. They also expand their pancreatic islet populations and improve beta cell function. When the brown adipose depot is removed from normoglycemic high fat-fed mice, fasting blood glucose and glucose tolerance revert to unhealthy levels. This occurs naturally and spontaneously on a high fat diet, with no temperature or genetic manipulation. We identified 267 genes whose expression changes in the brown adipose when the mice resolve their unhealthy glycemic parameters, and find the expanded tissue has a ‘healthier’ expression profile. Understanding the physiologic and genetic underpinnings of this phenomenon in SM/J mice will open the door for innovative therapies aimed at improving glycemic control.
Footnotes
↵* Indicates co-first authors