RESUMO
Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the ß-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the ß-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.
Assuntos
Tecido Adiposo/metabolismo , Adiposidade , Subunidade beta do Hormônio Folículoestimulante/antagonistas & inibidores , Termogênese , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo Bege/efeitos dos fármacos , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Anticorpos/imunologia , Anticorpos/farmacologia , Dieta Hiperlipídica/efeitos adversos , Feminino , Subunidade beta do Hormônio Folículoestimulante/imunologia , Haploinsuficiência , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Obesidade/tratamento farmacológico , Obesidade/prevenção & controle , Osteoporose/tratamento farmacológico , Ovariectomia , Consumo de Oxigênio/efeitos dos fármacos , Receptores do FSH/antagonistas & inibidores , Receptores do FSH/genética , Receptores do FSH/metabolismo , Termogênese/efeitos dos fármacos , Proteína Desacopladora 1/biossínteseRESUMO
IMPACT STATEMENT: Decellularized tissue matrices are popular as scaffolding materials for tissue engineering application. However, it is unclear whether interspecies differences in tissue parameters influence the quality of tissue grafts that are engineered using human stem cells. In this study, decellularized cow and human bone scaffolds were compared for engineering bone grafts using human induced pluripotent stem cell-derived mesodermal progenitor cells and despite minor differences in architecture and mass composition, both scaffolds equally support cell viability and tissue mineralization. Decellularized cow bone scaffolds therefore represent a suitable and more affordable alternative for engineering human bone grafts for basic and applied research.