FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice.

نویسندگان

  • Sheila Bornstein
  • Sue A Brown
  • Phuong T Le
  • Xunde Wang
  • Victoria DeMambro
  • Mark C Horowitz
  • Ormond MacDougald
  • Roland Baron
  • Sutada Lotinun
  • Gerard Karsenty
  • Wei Wei
  • Mathieu Ferron
  • Christopher S Kovacs
  • David Clemmons
  • Yihong Wan
  • Clifford J Rosen
چکیده

Lactation is associated with significant alterations in both body composition and bone mass. Systemic and local skeletal factors such as receptor activator of nuclear factor κ-B ligand (RANKL), PTHrP, calcitonin, and estrogen are known to regulate bone remodeling during and after lactation. Fibroblast growth factor 21 (FGF-21) may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation. In this study, we hypothesized that the metabolic changes during lactation were due in part to increased circulating FGF-21, which in turn could accentuate bone loss. We longitudinally characterized body composition in C57BL/6J (B6) mice during (day 7 and day 21 of lactation) and after normal lactation (day 21 postlactation). At day 7 of lactation, areal bone density declined by 10% (P < .001), bone resorption increased (P < .0001), percent fat decreased by 20%, energy expenditure increased (P < .01), and markers of brown-like adipogenesis were suppressed in the inguinal depot and in preformed brown adipose tissue. At day 7 of lactation there was a 2.4-fold increase in serum FGF-21 vs baseline (P < .0001), a 8-fold increase in hepatic FGF-21 mRNA (P < .03), a 2-fold increase in undercarboxylated osteocalcin (Glu13 OCn) (P < .01), and enhanced insulin sensitivity. Recovery of total areal bone density was noted at day 21 of lactation, whereas the femoral trabecular bone volume fraction was still reduced (P < .01). Because FGF-21 levels rose rapidly at day 7 of lactation in B6 lactating mice, we next examined lactating mice with a deletion in the Fgf21 gene. Trabecular and cortical bone masses were maintained throughout lactation in FGF-21(-/-) mice, and pup growth was normal. Compared with lactating control mice, lactating FGF-21(-/-) mice exhibited an increase in bone formation, but no change in bone resorption. In conclusion, in addition to changes in calciotropic hormones, systemic FGF-21 plays a role in skeletal remodeling and changes in body composition during lactation in B6 mice.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effect of neuregulin-1 on the auditory cortex in adult C57BL/6J mice

Objective(s): We sought to explore whether neuregulin-1(NRG1) would have a protective effect on the auditory cortices of adult C57BL/6J mice.Materials and Methods: We used RTPCR and Western blot (WB) to detect the expression of NRG1 and ERBB4 (the receptor of NRG1) in the auditory cortices of C57BL/6J mice of different ages (6–8 weeks an...

متن کامل

Ursolic acid induces myoglobin expression and skeletal muscle remodeling in mice

Introduction: Ursolic Acid (UA) is a lipophilic triterpenoid compound, found in large amounts in apple peel. Anabolic effects of UA on the skeletal muscle and the role of this tissue as a key regulator of systematic aging aroused this question in mind whether UA might amend skeletal muscle performances such as myoglobin expression and also whether it switches skeletal muscle fibers from glyc...

متن کامل

ZnT4 (SLC30A4)-null ("lethal milk") mice have defects in mammary gland secretion and hallmarks of precocious involution during lactation.

During lactation, highly specialized secretory mammary epithelial cells (MECs) produce and secrete huge quantities of nutrients and nonnutritive factors into breast milk. The zinc (Zn) transporter ZnT4 (SLC30A4) transports Zn into the trans-Golgi apparatus for lactose synthesis, and across the apical cell membrane for efflux from MECs into milk. This is consistent with observations in "lethal m...

متن کامل

Reproductive and developmental outcomes, and influence on maternal and offspring tissue mineral concentrations, of (−)-epicatechin, (+)-catechin, and rutin ingestion prior to, and during pregnancy and lactation in C57BL/6J mice

Maternal nutrition can have a significant effect on developmental processes during pregnancy and lactation. While certain flavonoids have been postulated to be beneficial for health, little is known about the effects of ingestion during pregnancy and lactation on the mother and progeny. We report on the effects of maternal consumption of high levels of certain flavonoids on reproductive and dev...

متن کامل

Novel Lesions of Bones and Joints Associated with Chikungunya Virus Infection in Two Mouse Models of Disease: New Insights into Disease Pathogenesis

Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Endocrinology

دوره 155 9  شماره 

صفحات  -

تاریخ انتشار 2014