Adiponectin receptor 1 could explain the sex differences in molecular basis of cognitive improvements induced by exercise training in type 2 diabetic rats

Abstract

Adipokines dysregulation, the main reason for cognitive impairments (CI) induced by diabetes, shows a sex-dependent pattern inherently and in response to exercise. This study aimed to compare the attenuating effect of 8-week high intensity-interval training (HIIT) on type 2 diabetes (T2D)-induced CI between male and female rats with a special focus on adiponectin and leptin. 28 male & 28 female Wistar rats with an average age of 8 weeks were randomly assigned into four groups: control (Con), exercise (EX), Diabetes (T2D), and Type 2 diabetes + exercise (T2D + Ex). Rats in EX and T2D + EX groups performed HIIT for eight weeks (80–100% Vmax, 4–10 intervals). T2D was induced by 2 months of a high-fat diet and a single dose of STZ (35 mg/kg) administration. Leptin and adiponectin levels in serum were measured along with hippocampal expression of leptin and adiponectin receptors, AMP-activated protein kinase (AMPK), dephosphorylated glycogen synthase kinase-3 beta (Dep-GSK3β), Tau, and beta-amyloid (Aβ). Homeostasis model assessments (HOMAs) and quantitative insulin-sensitivity check index (QUICKI) indices were calculated. Our results showed that following T2D, serum levels of APN, and hippocampal levels of adiponectin receptor 1 (APNR1) were higher and HOMA-IR was lower in female than male rats (P < 0.05). However, after 8 weeks of HIIT, hippocampal levels of APNR1 and AMPK as well as QUICKI were lower and hippocampal levels of GSK, Tau, and Aβ were higher in females compared to male rats (P < 0.05). While the risk of CI following T2D was more in male than female rats HIIT showed a more ameliorating effect in male animals with APN1 as the main player.

Lung molecular and histological changes in type 2 diabetic rats and its improvement by high-intensity interval training

“…The trends of FBG and BW changes (Table 3 ) approved the T2D induction and were in line with other previous studies [ 25 , 35 , 36 ] .Also, we showed the serum insulin reduction in T2D rats in our previous research [ 35 ].In addition, as reported in our previous publications, food intake was increased owing to T2D (polyphagia) and we demonstrated that HIIT may modulate appetite regulation in rats with T2D through leptin signaling [ 35 ].…”

Exercise training improves diabetic renal injury by reducing fetuin-A, oxidative stress and inflammation in type 2 diabetic rats

“…A direct relationship between fetuin-A and insulin resistance is known [ 58 ]. Moreover, there is an inverse relationship between fetuin-A and insulin resistance with adiponectin [ [59] , [60] , [61] ]. Our previous study with the same design showed that HIIT could increase serum adiponectin following T2D [ 62 ].…”

ATP releasing channels and the ameliorative effects of high intensity interval training on diabetic heart: a multifaceted analysis

“…We used K1 protocol which has been designed in our lab and the details can be fined in our previous publications 35 – 38 . In summary, the animals in the TR and T2D + TR groups were familiarized with treadmill (made by Tajhiz Gostar Co , Iran) twice a day for 5 days, 10 min per day with a zero-incline and a speed of 8 m per minute 39 . Then they performed an incremental running test to determine their maximum running speed (V max ).…”

“…In this test, the rats ran for 2 min at a speed of 6 m per minute and zero -incline, and every 2 min, 2 m per minute were added to the speed until they could not maintain the speed. The last attempt of each rat was considered Vmax 39 , 40 . The V max was used for designed the HIIT program for eight weeks (80–100% V max , 4–10 intervals).…”