Treatment with an inhibitor of fatty acid synthase attenuates bone loss in ovariectomized mice.
Bone
; 122: 114-122, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30779961
ABSTRACT
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 6â¯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 serum glucose or calciotropic hormones. These effects were associated with attenuation of bone loss and normalization of the bone phenotype in the cerulenin-treated OVX group compared to the vehicle-treated OVX group. Our results demonstrate that inhibition of FAS enhances bone formation, induces uncoupling between osteoblasts and osteoclasts, and favors mineralization, thus providing evidence that inhibition of FAS could constitute a new anabolic therapy for osteoporosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reabsorção Óssea
/
Ovariectomia
/
Inibidores Enzimáticos
/
Ácido Graxo Sintases
Limite:
Animals
Idioma:
En
Revista:
Bone
Assunto da revista:
METABOLISMO
/
ORTOPEDIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Colômbia