Effects of dietary restriction, methionine restriction, and pioglitazone on metabolic profile, blood glucose regulation, and bone quality in male middle-aged Sprague-Dawley rats.

OBJECTIVE

To investigate the effects of dietary restriction (DR), methionine restriction (MR), and pioglitazone (PIO) on energy metabolism, bone metabolism, and bone quality.

METHODS AND PROCEDURES: Six-month-old male Sprague-Dawley (SD) rats were subjected to: 1) control (CON) diet, 2) 40% dietary restriction (DR), 3) 80% dietary methionine restriction (MR), or 4) oral pioglitazone (PIO) treatment for 9 wk.

RESULTS

Compared with the CON group, the DR group experienced lower body weight (BW) gain and epididymal fat tissue weight, whereas the PIO group had higher BW gain. DR, MR, and PIO demonstrated distinct effects on serum markers of energy metabolism, aging, and inflammation, despite the fact that all interventions increased insulin sensitivity and glucose tolerance compared to the CON group (P < 0.05). Procollagen type 1 N-terminal propeptide (P1NP), a serum bone formation marker, was lower in DR-, MR-, and PIO-treated rats than in CON rats, while C-terminal telopeptide of type I collagen (CTX-1), as a serum bone resorption marker, showed no difference among groups. In histomorphometry and densitometry, the PIO group had a comprehensive loss in cancellous bone structures, bone mineral density (BMD) and/or bone mineral content (BMC) in tibiae and femora, as well as a lower cortical BMD of tibiae when compared with the CON group (P < 0.05). The bone mineral loss in the DR and MR groups was minor, such that both groups were lower in cancellous BMD of tibiae, and the MR group was lower in cancellous BMC of tibiae and femora when compared with the CON group (P < 0.05). In dimensional measurements, the PIO group had lower cortical thickness than the CON group in femora (P < 0.05).

CONCLUSION

While all interventions improved energy metabolism, DR and MR resulted in a minor compromise in bone mineral regulation relative to pioglitazone treatment in male SD rats.