Maternal high-fat diet consumption enhances offspring susceptibility to DSS-induced colitis in mice

Abstract

Objective: Maternal high-fat diet (HFD) may alter the offspring intestinal immune system, thereby enhancing susceptibility toward 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 sulfate sodium (DSS)-induced colitis.

Methods: Dams were provided with either HFD (60%) or control diet. After weaning, female offspring from both groups were kept on 45% HFD. At 14 weeks of age, offspring were subjected to 2.5% DSS in drinking water for 5 days, followed by 5 days of recovery.

Results: Offspring from maternal HFD had higher body weight gain before DSS induction and had 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. HFD offspring had an elevated histopathological score and interleukin (IL)-1β, IL-6, and IL-17 expression with upregulated NF-κB signaling. Maternal HFD resulted in enhanced neutrophil infiltration associated with elevated expression of monocyte chemoattractant protein-1. Furthermore, maternal HFD suppressed AMP-activated protein kinase activity and decreased sirtuin 1 and p53 protein contents in offspring gut.

Conclusions: Maternal HFD consumption predisposes offspring to a higher susceptibility to develop inflammatory bowel disease.

Fig. 1.

Experimental design. A. Maternal and offspring dietary treatment timeframe. B. Offspring mice at age of 14-week-old were subjected to 2.5% DSS water for 5 days followed by a 5 days recovery. Offspring of both maternal HFD and CON groups were fed with a 45% HFD (45% energy from fat) from weaning to necropsy.

Fig. 2

Body and organ weight in offspring of CON (□) or HFD (■) fed dams at necropsy. (A) Body weight, (B) Organ weight, (C) Fats weight, (D) Representative images of hematoxylin and eosin (H&E) staining of visceral adipose tissue section, (E) Adipocyte diameter (μm), and (F) Adipocyte area (μm²). Sub = Subcutaneous fats, BAT = Brown adipose tissue, and Vis = Visceral fats. Means ± SEM, n = 9, *: P ≤ 0.05.

Fig. 3

Symptoms of DSS-induced colitis in offspring of CON (□) or HFD (■) fed dams. (A) Weekly body weight of offspring after weaning and before DSS treatment, (B) Body weight loss and (C) Disease activity index during DSS-treatment and recovery process, a higher score correlates with severer symptoms. Means ± SEM, n = 9, *: P ≤ 0.05, **: P ≤ 0.01, and ***: P ≤ 0.001.

Fig. 4

Histopathological score and inflammatory mediators in offspring of CON (□) or HFD (■) fed dams. (A) Representative images of H&E staining of distal colonic sections, (B) Histopathological score, (C) mRNA expression of pro-inflammatory cytokines, (D-F) Representative immunoblotting bands and statistical data of p65, IκB-α and IL-6. Means ± SEM, n = 9, *: P ≤ 0.05, #: P ≤ 0.10.

Fig. 5

Neutrophil immunohistochemical staining in distal colonic tissues of offspring of CON (□) or HFD (■) fed dams. (A) Representative images of neutrophil staining, (B) Neutrophil infiltration score, (C) mRNA expression of MCP-1, (D-F) Representative immunoblotting bands and statistical data of p38 and ERK1/2. Means ± SEM, n = 9, *: P ≤ 0.05, #: P ≤ 0.10.

Fig. 6

AMP-activated protein kinase (AMPK) signaling in the colon of offspring of CON (□) or HFD (■) fed dams. (A) Representative immunoblotting bands, (B) Relative protein expression of AMPK, (C) Relative protein expression of SIRT1 and p53. Means ± SEM, n = 9, *: P ≤ 0.05.