Interaction of Pre‐natal and Post‐Weaning High Fat Diet on Adult Mouse Skeletal Muscle Vitamin D Homeostasis

Vitamin D (VD), lower in obesity, is implicated in skeletal muscle development and function. We tested the idea that pre‐natal (PRE) and post‐weaning (POST) high fat (HF) diet, previously shown to cause obesity and glucose intolerance, would alter the expression of markers of VD receptivity (VD receptor, VDR) and synthesis (CYP27B1, encodes 1‐α‐hydroxylase) in offspring skeletal muscle. C57 mice were fed HF (45% kcal fat) or control (C, 7% kcal fat) diet in PRE (from 6 weeks preconception and throughout weaning) and/or POST periods (HF/HF, HF/C, C/HF, C/C group, n=4‐5 per group). In 15 week old male extensor digitorum longus (EDL), soleus and vastus lateralis muscle ( m ), levels of CYP27B1 and VDR mRNA were measured by PCR, and analysed by ANOVA. CYP27B1 mRNA levels in vastus m (p<0.05) and EDL m (p<0.01) (not soleus m ) were affected by an interaction between PRE and POST HF diet: in vastus m POST HF reduced CYP27B1 mRNA most strongly in PRE C animals (C/HF vs . C/C, p<0.05), and in EDL m the increased CYP27B1 mRNA with PRE HF diet (HF/C vs. CC, p<0.01) was reduced when mismatch between PRE and POST HF diet was minimized (HF/HF). In EDL m , increased VDR mRNA with PRE HF diet (HF/C vs. CC, p<0.1) disappeared when the mismatch between PRE and POST HF diet was minimized (HF/HF). Thus VD availability and receptivity in skeletal muscle may be less affected by HF diet when the mismatch between HF in PRE and POST periods is minimized. This is muscle bed‐specific, possibly reflecting myofibre type composition, and could affect muscle glucose handling. Supported by Diabetes UK