Improved Glucose Control is Associated with Caloric Intake, but not Body Weight in Diet‐Induced Obese Mice

Abstract

Alternate day fasting (ADF) and caloric restriction are common and effective diets for weight loss in both rodents and humans. Weight loss is associated with improved circulating glucose control. However, the improvement in glucose homeostasis is associated with total caloric intake, but not body weight in genetically obese mice on an ADF diet. We therefore tested the hypothesis that improved glucose control similarly would be related to caloric intake, but not body weight, in diet‐induced obese mice. At the experiment onset, high fat fed male mice (n=25) weighed (41.0±3.3 g, mean±SD) significantly greater, p<0.001, than low fat fed mice (24.2±2.6 g (n=11)). To induce weight loss, diet‐induced obese mice were assigned to either 1) low fat food ADF, 2) low fat ad libitum food availability, 3) high fat caloric restriction (CR=75%), or 4) high fat food ADF (n=5 for each group). A group of mice (n=5) continued on a high fat ad libitum diet. After six weeks of diet manipulation, low fat ADF mice lost ~11g, low fat ad lib mice lost ~8.5g, while the high fat CR group and high fat ADF groups both lost ~5 grams. Glucose tolerance tests were performed after six weeks of diet manipulation, and area under the curve (AUC) was calculated over a two‐hour period. All diet manipulations led to increased glucose tolerance compared to high fat ad libitum mice (p<0.001 for all comparisons). We found that AUC positively correlated with caloric intake (r2=0.7361, p<0.001), but not with body weight (r2=0.06, p=0.169), or food fat content. There were no significant differences in glucose tolerance among the ADF and CR groups; however, the ADF groups had significantly lower AUCs than all other groups (p<0.05 for all comparisons). In total, these data suggest that 1) these diet manipulations lead to both increased glucose control and weight loss, and 2) body weight is not a good predictor of glucose control.