Obesity and Type 2 Diabetes T2D

Obesity is a medical condition in which excess body fat has accumulated. Type 2 Diabetes (T2B) is a disease characterized by high blood sugar and insulin resistance.

Diet-induced obesity and cognitive decline

In humans, a western-style diet with high amounts of fats and carbohydrates eventually leads to metabolic syndrome, a risk factor for diabetes mellitus type 2 (T2DM). Both metabolic syndrome and T2DM are risk factors in the development of cognitive decline and dementia. When mice are fed a High Fat (HF) diet or a diet with additional Cholesterol and Fructose (HFCF) they become obese in comparison with regular chow fed mice. At Sylics we observed detrimental effects of these diets on cognitive performance of mice, for instance in the Morris Water Maze.

Db/db mouse model of obesity

Db/db mice are a model of obesity and diabetes. These mice have a deficient leptin receptor, because of a homozygous point mutation in the leptin receptor-encoding gene. This receptor responds to fat-secreted leptin, which plays a key role in regulation of body weight. In depth characterization of the model at Sylics showed profound behavioral impairments related to activity, which makes this model less suitable for cognitive testing in comparison with the the HF and HFCF diet fed models.

Non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the name of a range of conditions caused by a build-up of fat in the liver. This condition is most frequently caused by unhealthy life style and diet and seen in people that are overweight or obese. In approximately 20 – 30 % of cases, this condition progresses into chronic inflammation in the liver (NASH) leading to liver cirrhosis. High amounts of fructose consumption contribute to this condition. Feeding mice with a diet rich in fat and additional Cholesterol and Fructose (HFCF) induces features of NAFLD and NASH, as well as behavioral and cognitive impairments. HFCF diet fed mice show impairments in the reversal stage of the Morris Water Maze.

Swim path of a trained mouse in the Morris Water Maze (MWM) during a probe trial after removal of the escape platform.

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