Preptin Deficiency Does Not Protect against High‐Fat Diet‐Induced Metabolic Dysfunction or Bone Loss in Mice

Preptin is derived from the cleavage of E-peptide pro-insulin-like growth factor (IGF)-II and an insulin secretagogue. Observational studies have linked elevated circulating preptin to metabolic dysfunction in humans; however, a causal role for has not been established. Additionally, can promote osteoblast proliferation differentiation, suggesting link with skeletal health. We previously described global knockout (KO) model. In this study, we sought uncover impact KO mice on response moderately high-fat diet (HFD) low-fat (LFD). HFD groups had higher weight fat mass gain, lower trabecular cortical bone volume fracture load, liver triglycerides. males, deficiency led blood glucose than wild-type (WT) under LFD conditions. This was accompanied by differences microarchitecture, including fraction, number, thickness. These were absent female mice, although females HFD-driven increase triglycerides that WT mice. Female increased glucose-stimulated secretion conditions Overall, may detrimental metabolism positive health male protect against storage while enabling islet compensation When consider serum levels are humans both sexes pathological states which elevated, comorbidity risk needs be better understood. © 2023 The Authors. JBMR Plus published Wiley Periodicals LLC behalf American Society Bone Mineral Research.