1008 Promotes Reproductive Function and Cognitive Activity in Aged Male Mice with High-Fat-Diet-Induced Obesity by Altering Metabolic Parameters and Alleviating Testicular Oxidative Damage, Inflammation and Apoptosis.

The effects of 1008 (LP1008) on age-related cognitive impairment and skeletal muscle atrophy have been reported previously. However, its role in obesity- and age-related hypogonadism has yet to be explored. This study investigates the therapeutic efficacy of low- and high-dose LP1008 in a high-fat-diet-fed male mouse model. Mice at 37 weeks of age were fed a standard diet ( = 8) or a 45% high-fat diet for 28 weeks, and the high-fat-diet-fed mice were divided into vehicle, low-dose and high-dose LP1008 groups ( = 8 per group) on the basis of the treatment administered for an additional 8 weeks. We found that LP1008 suppressed the increases in total cholesterol levels and liver function parameters and alleviated histological changes in the brain, ileum, gastrocnemius muscle and testes. In terms of reproductive function, LP1008 attenuated the decreases in sperm quality, sperm maturity, testosterone levels and levels of enzymes involved in testosterone biosynthesis. Furthermore, LP1008 altered impairments in spatial learning and memory and induced slight alterations in the gut microbiota. Moreover, LP1008 exerted antioxidant, anti-inflammatory and anti-apoptotic effects in aged, obese male mice. LP1008 reversed diet-induced obesity, age-related reproductive dysfunction and pathological damage by increasing testosterone levels and altering the gut microbiome through the regulation of mediators involved in oxidative stress, apoptosis and inflammation.