Non-alcoholic Fatty pancreas disease pathogenesis: a role fordevelopmental programming and altered circadian rhythms.

Francesca Rappa, Valerio Pazienza, Giuseppe Fusai, Joaquim Pombo, Angelina Mouralidarane, Ruma Saraswati, Paul D. Taylor, Shuvra Ray, Lucilla Poston, Francesca Rappa, Chiara Saracino, Rebeca Carter, Jude A. Oben, Manlio Vinciguerra, Junpei Soeda, Marco Novelli

Risultato della ricerca: Articlepeer review

29 Citazioni (Scopus)

Abstract

OBJECTIVES: Emerging evidence suggests that maternal obesity (MO) predisposesoffspring to obesity and the recently described non-alcoholic fatty pancreasdisease (NAFPD) but involved mechanisms remain unclear. Using apathophysiologically relevant murine model, we here investigated a role for thebiological clock - molecular core circadian genes (CCG) in the generation ofNAFPD.DESIGN: Female C57BL6 mice were fed an obesogenic diet (OD) or standard chow (SC)for 6 weeks, prior to pregnancy and throughout gestation and lactation: resultingoffspring were subsequently weaned onto either OD (Ob_Ob and Con_Ob) or standard chow (Ob_Con and Con_Con) for 6 months. Biochemical, pro-inflammatory andpro-fibrogenic markers associated with NAFPD were then evaluated and CCG mRNAexpression in the pancreas determined.RESULTS: Offspring of obese dams weaned on to OD (Ob_Ob) had significantlyincreased (p≤0.05): bodyweight, pancreatic triglycerides, macrovesicularpancreatic fatty-infiltration, and pancreatic mRNA expression of TNF-α, IL-6,α-SMA, TGF-β and increased collagen compared to offspring of control dams weaned on to control chow (Con_Con). Analyses of CCG expression demonstrated a phaseshift in CLOCK (-4.818, p<0.01), REV-ERB-α (-1.4,p<0.05) and Per2 (3.27,p<0.05)in association with decreased amplitude in BMAL-1 (-0.914,p<0.05) and PER2(1.18,p<0.005) in Ob_Ob compared to Con_Con. 2-way ANOVA revealed significantinteraction between MO and post-weaning OD in expression of CLOCK (p<0.005), PER1(p<0.005) and PER2 (p<0.05) whilst MO alone influenced the observed rhythmicvariance in expression of all 5 measured CCG.CONCLUSIONS: Fetal and neonatal exposure to a maternal obesogenic environmentinteracts with a post-natal hyper-calorific environment to induce offspring NAFPDthrough mechanisms involving perturbations in CCG expression.
Lingua originaleEnglish
Numero di pagine12
RivistaPLoS One
Volume9
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1100.1100???
  • General

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