Leprdb/+ dams protect wild-type male offspring bone strength from the detrimental effects of a high-fat diet

Arin K. Oestreich, Anthony Onuzuriuke, Xiaomei Yao, Omonseigho Talton, Yong Wang, Ferris M. Pfeiffer, Laura C. Schulz, Charlotte L. Phillips

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The prevalence of maternal obesity is increasing at an alarming rate and increases the life-long risk of developing cardiometabolic disease in adult offspring. Leptin, an adipokine, is systemically elevated in the obese milieu. We recently showed that maternal hyperleptinemia without obesity improves offspring insulin sensitivity and glucose tolerance while protecting against weight gain on a high-fat, high-sugar (HFD). Here, we investigate the effect of maternal hyperleptinemia on offspring bone by using 2 independent maternal models. First, we compared wild-type (WT) offspring from severely hyperleptinemic Leprdb/+ (DB/+) dams with those from WT dams. In the second model, WT females were implanted with miniosmotic pumps that released either saline (group SAL) or leptin (group LEP; 650ng/hour) and the WT offspring were compared. At 23 weeks of age, a subset of offspring were challenged with a HFD for 8 weeks. When the offspring were 31 weeks of age, bone geometry, strength, and material properties were investigated. The HFD increased trabecular bone volume but decreased both total breaking strength and material strength of femora from the offspring of WT dams. However, male offspring of DB/+ dams were protected from the detrimental effects of a HFD, while offspring of LEP dams were not. Further material analysis revealed a modest decrease in advanced glycation end product accumulation coupled with increased collagen crosslinking in male offspring from DB/+ dams on a HFD. These data suggest that while maternal leptin may protect bone quality from the effects of a HFD, additional factors of the maternal environment controlled by leptin receptor signaling are likely also involved.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalEndocrinology (United States)
Issue number8
StatePublished - 2021


  • Adipokine
  • Metabolism
  • Obesity
  • Raman spectroscopy


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