TY - JOUR
T1 - High-intensity interval training attenuates ketogenic diet-induced liver fibrosis in type 2 diabetic mice by ameliorating TGF-β1/smad signaling
AU - Zhang, Qiang
AU - Shen, Fei
AU - Shen, Wen Qing
AU - Xia, Jie
AU - Wang, Jing
AU - Zhao, Yu
AU - Zhang, Zhe
AU - Sun, Yi
AU - Qian, Min
AU - Ding, Shu Zhe
N1 - Publisher Copyright:
© 2020 Zhang et al.
PY - 2020
Y1 - 2020
N2 - Objective: Ketogenic diet (KD) and high-intensity interval training (HIIT) have preclinical benefits for type 2 diabetes (Db). However, the health risks of long-term KD use in diabetes should be ascertained and prevented. We hypothesized that KD-induced liver fibrosis in type 2 diabetic mice could be ameliorated by HIIT. Methods: Streptozotocin-induced type 2 diabetic mice were divided into high-fat diet (HFD) control (Db+HFD+Sed), KD control (Db+KD+Sed), HFD coupled with HIIT (Db +HFD+HIIT), and KD coupled with HIIT (Db+KD+HIIT) groups (n=6, per group). Control mice were kept in sedentary (Sed), while HIIT group mice underwent 40-minute high-intensity interval training three alternate days per week. After 8-week intervention, the indicators of body weight and insulin resistance, oxidative stress markers, hepatic fibrosis, genetic and protein expression of related pathways were tested. Results: We found that fasting blood glucose level was reduced in the Db+HFD+HIIT, Db +KD+Sed, and Db+KD+HIIT groups. Insulin sensitivity was increased in diabetic mice of these groups, whereas ROS levels were decreased in mice that underwent HIIT. The immunohistochemical staining of liver, serum index, and hepatic parameters of diabetic mice in the KD group revealed liver fibrosis, which was significantly attenuated by HIIT. Besides, these effects of HIIT were the outcome of hepatic stellate cell’s inactivation, reduced protein expression of matrix metalloproteinases and tissue inhibitor of metallopro-teinases, and the inhibition of TGF-β1/Smad signaling. Conclusion: KD had a profound fibrotic effect on the liver of type 2 diabetic mice, whereas HIIT ameliorated this effect. KD did not show any apparent benefit as far as glucose tolerance and homeostasis were concerned. Concisely, our results demonstrated that KD should be coupled with HIIT for the prevention and preclinical mitigation of type 2 diabetes.
AB - Objective: Ketogenic diet (KD) and high-intensity interval training (HIIT) have preclinical benefits for type 2 diabetes (Db). However, the health risks of long-term KD use in diabetes should be ascertained and prevented. We hypothesized that KD-induced liver fibrosis in type 2 diabetic mice could be ameliorated by HIIT. Methods: Streptozotocin-induced type 2 diabetic mice were divided into high-fat diet (HFD) control (Db+HFD+Sed), KD control (Db+KD+Sed), HFD coupled with HIIT (Db +HFD+HIIT), and KD coupled with HIIT (Db+KD+HIIT) groups (n=6, per group). Control mice were kept in sedentary (Sed), while HIIT group mice underwent 40-minute high-intensity interval training three alternate days per week. After 8-week intervention, the indicators of body weight and insulin resistance, oxidative stress markers, hepatic fibrosis, genetic and protein expression of related pathways were tested. Results: We found that fasting blood glucose level was reduced in the Db+HFD+HIIT, Db +KD+Sed, and Db+KD+HIIT groups. Insulin sensitivity was increased in diabetic mice of these groups, whereas ROS levels were decreased in mice that underwent HIIT. The immunohistochemical staining of liver, serum index, and hepatic parameters of diabetic mice in the KD group revealed liver fibrosis, which was significantly attenuated by HIIT. Besides, these effects of HIIT were the outcome of hepatic stellate cell’s inactivation, reduced protein expression of matrix metalloproteinases and tissue inhibitor of metallopro-teinases, and the inhibition of TGF-β1/Smad signaling. Conclusion: KD had a profound fibrotic effect on the liver of type 2 diabetic mice, whereas HIIT ameliorated this effect. KD did not show any apparent benefit as far as glucose tolerance and homeostasis were concerned. Concisely, our results demonstrated that KD should be coupled with HIIT for the prevention and preclinical mitigation of type 2 diabetes.
KW - Diabetes
KW - Hepatic fibrosis
KW - High-intensity interval training
KW - Ketogenic diet
KW - ROS
KW - TGF-β1/Smad signal
UR - https://www.scopus.com/pages/publications/85096071534
U2 - 10.2147/DMSO.S275660
DO - 10.2147/DMSO.S275660
M3 - 文章
AN - SCOPUS:85096071534
SN - 1178-7007
VL - 13
SP - 4209
EP - 4219
JO - Diabetes, Metabolic Syndrome and Obesity
JF - Diabetes, Metabolic Syndrome and Obesity
ER -
