Self-selected macronutrient diet affects energy and glucose metabolism in brown fat-ablated mice

Obese transgenic UCP-DTA mice have largely ablated brown adipose tissue and develop obesity and diabetes, which are highly susceptible to a high-fat diet. We investigated macronutrient self-selection and its effect on development of obesity, diabetes, and energy homeostasis in UCP-DTA mice.

UCP-DTA and wild-type littermates were fed a semisynthetic macronutrient choice diet (CD) ad libitum from weaning until 17 weeks. Energy homeostasis was assessed by measurement of food intake, food digestibility, body composition, and energy expenditure. Diabetes was assessed by blood glucose measurements and insulin tolerance test.

Wild-type and UCP-DTA mice showed a high fat preference and increased energy digestion on CD compared with a low-fat standard diet. On CD, wild-type mice accumulated less body fat (16.9%) than UCP-DTA (32.6%) mice, although they had a higher overall energy intake. Compared with wild-type mice, resting metabolic rate was reduced in UCP-DTA mice irrespective of diet. UCP-DTA mice progressively decreased their carbohydrate intake, resulting in an almost complete avoidance of carbohydrate. UCP-DTA mice developed severe insulin resistance but showed decreased fed and fasted blood glucose on CD.

In contrast to wild-type mice, UCP-DTA mice were not able to reduce their weight gain efficiency on CD. This suggests that, because of the high fat preference of the background strain and the increased metabolic efficiency, brown adipose tissue-deficient mice still develop obesity and insulin resistance on a macronutrient CD even when decreasing overall energy intake. Through the avoidance of carbohydrates, however, they are able to maintain normoglycemia.