Original Article A Choline-Deficient Diet Exacerbates Fatty Liver but Attenuates Insulin Resistance and Glucose Intolerance in Mice Fed a High-Fat Diet

Liver fat accumulation is proposed to link obesity and insulin resistance. To dissect the role of liver fat in the insulin resistance of diet-induced obesity, we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low-fat (10 % of calories) or high-fat (45 % of calories) diet for 8 weeks; during the final 4 weeks, diets were either choline deficient or choline supplemented. In choline re-plete animals, high-fat feeding induced weight gain, ele-vated liver triglycerides (171%), hyperinsulinemia, and glucose intolerance. Choline deficiency did not affect body or adipose depot weights but amplified liver fat accumula-tion with high-fat diet (281%, P < 0.01). However, choline deficiency lowered fasting plasma insulin (from 983 175 to 433 36 pmol/l, P < 0.01) and improved glucose tolerance on a high-fat diet. In mice on 30 % fat diet, cholin