Aerobic Exercise Improves Type 2 Diabetes Mellitus-Related Cognitive Impairment by Inhibiting JAK2/STAT3 and Enhancing AMPK/SIRT1 Pathways in Mice

Abstract

Type 2 diabetes mellitus (T2DM) is a prevalent risk factor for cognitive impairment. Aerobic exercise can improve T2DM-related cognitive impairment; however, the possible mechanisms remain elusive. Thus, we assessed db/m mice and leptin receptor-deficient (db/db) mice that did or did not perform aerobic exercise (8 m/min, 60 min/day, and 5 days/week for 12 weeks). In this study, cognitive function was significantly impaired in the T2DM mice; aerobic exercise improved cognitive impairment through activating the AMPK/SIRT1 signalling pathway and inhibiting the JAK2/STAT3 signalling pathway in T2DM mice. However, after the application of RO8191 (JAK2 activator) or Compound C (AMPK inhibitor), the positive improvement of the exercise was evidently suppressed. Taken together, our data indicated that long-term aerobic exercise improves type 2 diabetes mellitus-related cognitive impairment by inhibiting JAK2/STAT3 and enhancing AMPK/SIRT1 pathways in mice.

Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes

“…Physical activity is widely advocated in the management of T2DM, and moreover, a mounting body of evidence suggests that exercise, which is a specific type of physical activity, has significant positive effects on the maintenance and enhancement of brain structure as well as function (Callisaya and Nosaka 2017 ). Similarly, AE has been recently confirmed as one effective way to improve T2DM-related cognitive impairment (Lin et al 2022 ).…”

The effect of progressive endurance training and extract of black winter truffle on proteins levels and expression of hippocampus α-synuclein and HSF1 in the healthy and diabetic rats

“…Thus, exercise may increase HSF1 through mechanisms such as increasing HSP70 and BDNF [ 19 ] and inhibiting GSK3 in the brain. Furthermore, some studies reported that aerobic exercise upregulates AMPK and SIRT1 [ 48 ]. Hence, it seems to explain the increase in the brain HSF1 levels caused by the endurance exercise performed in our study.…”

Aerobic Exercise Ameliorates Liver Injury in Db/Db Mice by Attenuating Oxidative Stress, Apoptosis and Inflammation Through the Nrf2 and JAK2/STAT3 Signalling Pathways

“… 36 Previous studies have suggested that reasonable exercise could also perform its action by decreasing key enzymes of carbohydrate response element-binding protein (ChREBP), such as acetyl-CoA carboxylase and fatty acid synthesis, to recover lipid metabolism in the liver. 37 , 38 In addition, aerobic exercise could prevent diabetes by reducing haemoglobin A1C (A1C) levels, increasing peak oxygen consumption (VO2peak) 39 and significantly improving endothelial function, 27 cognitive impairment 40 and endotoxaemia caused by diabetes. 41 …”

“…36 Previous studies have suggested that reasonable exercise could also perform its action by decreasing key enzymes of carbohydrate response element-binding protein (ChREBP), such as acetyl-CoA carboxylase and fatty acid synthesis, to recover lipid metabolism in the liver. 37,38 In addition, aerobic exercise could prevent diabetes by reducing haemoglobin A1C (A1C) levels, increasing peak oxygen consumption (VO2peak) 39 and significantly improving endothelial function, 27 cognitive impairment 40 and endotoxaemia caused by diabetes. 41 Mounting evidence indicates that oxidative stress and subsequent inflammation are strictly related to liver diseases in diabetes, 42,43 and the initial cellular reaction to high glucose generates mitochondrial reactive oxygen species (ROS), which rapidly induce apoptotic cell death.…”