抄録
Background: Exenatide (EXE), a prototypical GLP-1R agonist, is known as glucoregulator, antiobesogenic and antidyslipidemic in hyperlipidic and hyperglucidic diet-induced obesity in rats (DIO). Objective: To evaluate bone effects of DIO and DIO treatment with EXE (DIO-E). Methods: 72-75-day-old male rats had access only to (i) hyperlipidic food (5.2 kcal/g) and 30% sucrose solution for drinking (1.2 kcal/mL), or (ii) received normocaloric diet (3 kcal/g) and were allowed to feed and to drink water ad libitum. 122-125-day-old rats with 20% overweight were selected from i as obese and those with normal weight were selected from ii as control (C) animals. Thus, obese animals remained untreated (DIO) or were treated with 10 μg EXE/kg sc (DIO-E) daily, for 20 days. Plasma levels of insulin (INS), leptin (LEP), osteocalcin (OCN), carboxy-terminal telopeptide of type 1 collagen (CTX-1) (ng/mL), as well as calcitonin (CT) and procollagen type 1 amino-terminal propeptide (P1NP) (pg/mL) were measured by ELISA. Bone mineral density of femur (BMDF) (g/cm3) was measured by X-rays. Results: DIO exhibited similar INS (12.9±1.83, n=4) and CT (2.80±1.05, n=4), higher LEP (0.33±0.04, n=5) and lower CTX-1 (0.48±0.22, n=3) than C. The treatment of DIO with EXE restored LEP (0.04±0.02, n=5), decreased CTX-1 (0.50±0.22, n=5) and increased CT (6.87±0.72, n=5). The levels of OCN (1.58±0.41, n=5), P1NP (92.64±16.89, n=5) and BMDF (1.9±0.07, n=5) of C and those of DIO and DIO-E were similar. Conclusions: Despite of increased LEP, decreased CTX-1 and normal OCN, P1NP and BMDF reflect a relative normal balance in bone turnover in DIO. Mechanical overloading due to high body mass is known as a factor that promotes this normal condition. Given that EXE decreases 14% body mass of DIO, the present study suggests that normalization of LEP and increased CT and decreased CTX-1 are concomitant beneficial effects of EXE that contribute for maintaining bone turnover under decreased mechanical load in DIO.
Supported by FAPESP, CNPq and CAPES
