Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in nonobese diabetic mice.
Impairment of gut epithelial barrier function is a key predisposing factor for inflammatory bowel disease, type 1 diabetes (T1D) and related autoimmune diseases. We hypothesized that maternal obesity induces gut inflammation and impairs epithelial barrier function in the offspring of nonobese diabetic (NOD) mice. Four-week-old female NOD/ShiLtJ mice were fed with a control diet (CON; 10% energy from fat) or a high-fat diet (HFD; 60% energy from fat) for 8 weeks to induce obesity and then mated. During pregnancy and lactation, mice were maintained in their respective diets. After weaning, all offspring were fed the CON diet. At 16 weeks of age, female offspring were subjected to in vivo intestinal permeability test, and then ileum was sampled for biochemical analyses. Inflammasome mediators, activated caspase-1 and mature forms of interleukin (IL)-1β and IL-18 were enhanced in offspring of obese mothers, which was associated with elevated serum tumor necrosis factor α level and inflammatory mediators. Consistently, abundance of oxidative stress markers including catalase, peroxiredoxin-4 and superoxide dismutase 1 was heightened in offspring ileum (P<.05). Furthermore, offspring from obese mothers had a higher intestinal permeability. Morphologically, maternal obesity reduced villi/crypt ratio in the ileum of offspring gut. In conclusion, maternal obesity induced inflammation and impaired gut barrier function in offspring of NOD mice. The enhanced gut permeability in HFD offspring might predispose them to the development of T1D and other gut permeability-associated diseases.
School of Food Science, Washington State University, Pullman, WA 99164, USA.
Yansong
Y
Xue
School of Food Science, Washington State University, Pullman, WA 99164, USA; Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA.
Hui
H
Wang
Department of Animal Science, Washington State University, Pullman, WA 99164, USA.
Min
M
Du
School of Food Science, Washington State University, Pullman, WA 99164, USA; School of Food Science, University of Idaho, Moscow, ID 83844, USA. Electronic address: meijun.zhu@wsu.edu.
Mei-Jun
MJ
Zhu
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D007079:Ileitis / Q000209:etiology* / Q000378:metabolism; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D039382:Maternal Nutritional Physiological Phenomena; D016688:Mice, Inbred NOD; D009765:Obesity / Q000503:physiopathology*; D010539:Permeability; D011247:Pregnancy
D000975:Antioxidants
Inflammation; Intestine; Maternal obesity; NOD; Offspring; Oxidative stress; Permeability; Tight junction proteins