Maternal high fat diet alters offspring susceptibility to DSS‐induced colitis

Abstract

ObjectiveMaternal high fat diet (HFD) may alter the offspring intestinal immune system thereby enhancing susceptibility towards inflammatory bowel disease. The objective of the current study was to investigate the impact of maternal HFD on offspring intestinal health using a mouse model of dextran sodium sulfate (DSS)‐induced colitis.MethodsDams were provided with either 60% HFD or control diet. After weaning female offspring from both groups were kept on 45% HFD. At 12‐weeks old, offspring were challenged to 2.5% DSS in drinking water for 5 days, followed by 5 days of recovery.ResultsOffspring from maternal HFD had higher body weight gain before DSS‐induction, higher liver and fat weights with increased adipocyte size at necropsy. When subjected to DSS‐treatment, HFD offspring had accelerated body weight loss and exaggerated disease activity index, accompanied with increased histopathological scores and up‐regulated pro‐inflammatory cytokine production and NF‐κB signaling. Concomitantly, maternal HFD resulted in enhanced neutrophil infiltration associated with elevated expression of monocyte chemoattractant protein‐1. Furthermore, maternal HFD suppressed AMP‐activated protein kinase (AMPK) activity, and decreased sirtuin 1 (SIRT1) and p53 protein contents in offspring gut.ConclusionMaternal HFD consumption predisposes offspring to develop inflammatory bowel disease (NIH R15HD073864).