Poster Topical Area: Diet and Cancer

Location: Auditorium

Poster Board Number: 226

P07-040 - Glycolysis Restriction Alters Physical and Metabolic Performance in Mice Fed a High-Fat Diet

Monday, Jun 11
8:00 AM – 3:00 PM

Objectives: Low-carbohydrate diet with unlimited calories has shown to decrease body weight for obese subjects. However, it is debated whether carbohydrate restriction has metabolic advantage for its variable weight loss.


Methods:
Five-week-old C57BL/6J male mice were divided into 4 groups: fed either a standard rodent chow (SD) or a high-fat diet (HFD), and received glycolytic inhibitor, 2-deoxyglucose (2-DG) (200 mg/kg/day) or water (W). In the first experiment, we examined the survival rate in respective group. In the second experiment, we recorded rectal temperature, body weight and amount of food intake once a day. In addition, we collected blood samples to measure β-hydroxybutyric acid, lactate, and total cholesterol levels on day 8.


Results:
High-fat diet-fed mice administered 2-DG led to an absolute mortality within 9 days, but the other 3 groups remained alive. Rectal temperature and body weight were consistent in all groups between days 1 and 4, but high-fat diet-fed mice administered 2-DG exhibited greater decreases in rectal temperature (Celsius degree) (SD+W, 38±0.5; SD+2-DG, 38±0.3; HFD+W, 38±0.1; HFD+2-DG, 33±1.1, mean±SEM (n=7 in each group, p<0.001, 1-way ANOVA), food intake (g/day) (SD+W, 3.3±0.2; SD+2-DG, 3.3±0.2; HFD+W, 2.5±0.15; HFD+2-DG, 0.01±0.15, p<0.001) and decline in body weight (g) (21±0.6; SD+2-DG, 21±0.4; HFD+W, 21±0.6; HFD+2-DG, 18±0.5, p=0.0003) than the other groups on day 8. In blood analysis, high-fat diet-fed mice administered 2-DG exhibited increases of β-hydroxybutyric acid (mmol/L) (SD+W, 0.5±0.09; SD+2-DG, 0.5±0.08; HFD+W, 0.5±0.08; HFD+2-DG, 1.7±0.3, p<0.001) and lactate levels (mmol/L) (SD+W, 2.5±0.4; SD+2-DG, 3.2±0.3; HFD+W, 2.0±0.4; HFD+2-DG, 5.6±1.6, p=0.0318). In addition, plasma cholesterol levels raised in high-fat diet-fed mice administered 2-DG (mg/dL) (SD+W, 56±3; SD+2-DG, 57±4; HFD+W, 117±11; HFD+2-DG, 256±29, p<0.0001), despite the decrease of food intake.


Conclusions:
This study suggests that carbohydrate is necessary for fundamental physical and metabolic performance in mice when lipid-rich diet is loaded.




Funding Source: JSPS KAKENHI Grant Number 26461076

CoAuthors: Yilin Hao – Heilongjiang Province Land Reclamation Bureau Hospital Management Center Baoquanling; Yoko Sekita-Hatakeyama – Nara Medical Universisty; Sumiharu Sakamoto – University of Miyazaki; Kazuo Kitamura – University of Miyazaki

Toshihiro Tsuruda

Senior Assistant Professor
University of Miyazaki
Miyazaki, Miyazaki, Japan