1515-PUB: Opposite Effects of Low-Carbohydrate High-Fat Diet on Metabolism in Humans and Mice

Abstract

Aims: Low-carbohydrate diet (LCD) , characterized by low consumption of carbohydrate and high intake of fat, is well known to decrease body weight and blood glucose in humans. However, in animal experiments, high-fat diet (HFD) is widely used to induce dietary obese model with metabolic disorders. The study aims to explore why LCD/HFD has the opposite effects on humans and animals. Methods: Twenty-two adults with overweight or obesity were enrolled to receive LCD for three weeks. The subjects were divided into two groups according to whether carbohydrate intake is below 10% by calories, and their weight loss and glucose homeostasis were compared. C57 mice were randomly assigned to five groups: chow diet (CD) , HFD with respectively 60%, 70% and 75% fat (cocoa butter) by calories and 60% fat (lard) by calories (60%HFD-L) , and metabolism of mice was evaluated. Results: In this trial, subjects who consumed less carbohydrate had greater weight loss and better glycemic control compared with the others. The questionnaires revealed that most of the subjects favored high-carbohydrate (HC) food rather than low-carbohydrate food. However, in mice, HFD groups showed more weight gain and higher blood glucose compared with CD group. When provided with CD and HFD at the same time, mice ate little CD. Besides, we found HFD group had lower mRNA level of Npy and Agrp and higher mRNA level of Pomc and Cartpt in hypothalamus in comparison with CD group. Among HFD with coco butter groups, mice took in more calories and gained more weight as the fat content in diet increases. Compared with HFD with coco butter groups, mice in 60%HFD-L group consumed even more calories, and had heavier body weight and poorer glucose metabolism. Conclusion: LCD has opposite effects on metabolism in humans and mice because of different food preferences. People prefer HC food while mice favor HFD. Mice consume more and feel less hungry when the diet contains higher proportion of fat, which leads to poorer metabolic status. Besides, mice prefer lard to coco butter. Disclosure X.Xia: None. L.Cai: None. Y.Gu: None. J.Yin: None. Funding National Natural Science Foundation of China (No. 82070885) ,Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (No. 20172025)