Treatment with an inhibitor of fatty acid synthase attenuates bone loss in ovariectomized mice
Sandra Bermeo, Ahmed Al Saedi, Christopher Vidal, Mamdouh Khalil, Manhui Pang, Bruce R Troen, Damian Myers, Gustavo Duque
BONE | ELSEVIER SCIENCE INC | Published : 2019
Bone and fat cells have an antagonistic relationship. Adipocytes exert a toxic effect on bone cells in vitro through the secretion of fatty acids, which are synthesized by fatty acid synthase (FAS). Inhibition of FAS in vitro rescues osteoblasts from fat-induced toxicity and cell death. In this study, we hypothesized that FAS inhibition would mitigate the loss of bone mass in ovariectomized (OVX) mice. We treated OVX C57BL/6 mice with cerulenin (a known inhibitor of FAS) for 6 weeks and compared their bone phenotype with vehicle-treated controls. Cerulenin-treated mice exhibited a significant decrease in body weight, triglycerides, leptin, and marrow and subcutaneous fat without changes in s..View full abstract
Awarded by Australian National Health and Medical Research Council
This study was supported by grants from the Australian National Health and Medical Research Council (NHMRC 632767), the Australian Institute for Musculoskeletal Science (AIMSS), the Nepean Medical Research Foundation, the U.S. Department of Veterans Affairs (Merit Review), and the Indian Trail Foundation. Support was also received from the Miami VAHS GRECC and Research Service. M. Hernandez and M. Rodriguez provided technical assistance. The authors would like to thank Professor David Handelsman for his continuous support to this study.