Postnatal PPARdelta activation and myostatin inhibition exert distinct yet complimentary effects on the metabolic profile of obese insulin-resistant mice.

Background: Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice.

Methodology/principal Findings: Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879.

Myostatin inhibition enhances the effects of exercise on performance and metabolic outcomes in aged mice.

The objective of this study was to examine the effects of short-term exercise training, myostatin inhibition (PF-354), and exercise+PF-354, all relative to a vehicle control, on performance and metabolic measures in 24-month-old mice. At study termination, PF-354-treated mice exhibited significantly greater muscle weights. Performance measures revealed that exercise+PF-354 increased treadmill running time and distance to exhaustion (more than twofold) and increased habitual activity.

Lasofoxifene enhances vaginal mucus formation without causing hypertrophy and increases estrogen receptor beta and androgen receptor in rats.

Objective: Lasofoxifene, a new selective estrogen-receptor modulator (SERM), shows efficacy in vaginal and vulvar atrophy in postmenopausal women. Here, we sought to explore the possible mechanisms of action for this effect in comparison with other SERMs using an immature ovariectomized rat model.

Design: SERMs (lasofoxifene, raloxifene, and tamoxifen) and 17alpha-ethinyl estradiol were administered orally to immature ovariectomized rats daily for 1 or 4 days.

Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib.

Objective: The ability of the potent cholesteryl ester transfer protein (CETP) inhibitor torcetrapib (CP-529,414) to raise high-density lipoprotein cholesterol (HDL-C) levels in healthy young subjects was tested in this initial phase 1 multidose study.

Methods And Results: Five groups of 8 subjects each were randomized to placebo (n=2) or torcetrapib (n=6) at 10, 30, 60, and 120 mg daily and 120 mg twice daily for 14 days. Torcetrapib was well tolerated, with all treated subjects completing the study.