|Xie, Linglin - Medical University Of North Dakota|
|Zhang, Ke - Medical University Of North Dakota|
|Rasmussen, Dane - Medical University Of North Dakota|
|Wang, Junpeng - Tufts University|
|Wu, Dayong - Tufts University|
|Johnson, W. Thomas - Retired ARS Employee|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2016
Publication Date: 1/31/2017
Publication URL: http://handle.nal.usda.gov/10113/5661745
Citation: Xie, L., Zhang, K., Rasmussen, D., Wang, J., Wu, D., Roemmich, J.N., Bundy, A.N., Johnson, W., Larson, K.J. 2017. Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring. Journal of Nutrition. doi: 10.1371/journal.pone.0169581.
Interpretive Summary: Investigators at the Grand Forks Human Nutrition Research Center had shown in a previous study that maternal undernutrition such as a low protein diet causes the offspring to become obese. They also demonstrated that obesity in such offspring is associated with an increased risk for type 2 diabetes. Since obesity is also associated with increased inflammatory immune cell numbers in fat tissue, they tested whether numbers of particular subsets of immune cells called M1 and M2 macrophages are different in the fat tissues of offspring whose mothers were fed a low protein diet. Type 1 or M1 macrophages are inflammatory cells that release a proinflammatory factor called interleukin 6 (IL-6) and these cells are found in higher numbers in obese compared to non-obese subjects. In contrast, type 2 or M2 macrophages are anti-inflammatory cells that are found in higher numbers in non-obese compared to obese subjects. A third group of cells called M1b have characteristics of both M1 and M2 macrophages. It is currently unknown whether maternal LP diet-induced offspring obesity is associated with changes in M1, M1b, or M2 cell numbers and expression of inflammatory factors in fat tissue. Using rat offspring whose mothers were fed a low protein diet during pregnancy and who were fed a high-fat diet post-weaning, the investigators tested whether increased fat tissue was correlated with changes in numbers of adipose tissue M1, M1b and M2 macrophages. Fat tissue growth rate was highest in maternal low protein and post-weaning high fat diet group. In the maternal low protein diet group, M1 cell numbers did not change while M2 cell numbers increased when the offspring were fed a high-fat diet. In the maternal normal protein group, both M1 and M2 cell numbers increased when fed a post-weaning high-fat diet. The ratio of M1 and M2 did not change with maternal and post weaning diets while M1b cell numbers increased in maternal normal protein and post-weaning high-fat diet group. However, those offspring who experienced a maternal low-protein diet and post-weaning high-fat diet had greater proinflammatory IL-6 expression. In summary, these results indicate that a maternal low-protein diet combined with a post-weaning high fat diet contributes to changes in M1, M1b and M2 cell numbers to increase fat tissue inflammation.
Technical Abstract: Adipose tissue macrophages (ATM) are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. However, it is not known whether maternal undernutrition increases ATM phenotypic expression in F1 offspring. Using a rat model of prenatal low protein (LP, 8% protein) diet followed by a postnatal high fat energy diet (HE, 45% fat) or low fat normal energy diet (NE, 10% fat) for 12 weeks, we investigated the effect of these diets on adiposity, programming of the offspring ATM phenotype, and the associated inflammatory response. Fat mass in newborn and 12-week old LP fed offspring was lower than that of normal protein (20%; NP) fed offspring; however, the adipose tissue growth rate was higher compared to the NP fed offspring. While LP did not affect the number of CD68+ or CD206+ cells in adipose tissue of NE offspring, it attenuated the number of these cells in offspring fed HE. LP resulted in a lower percentage of CD11c+CD206+ ATMs in offspring fed HE. Noteworthy, similar to HE treatment, LP increased gene expression of IL-6 within ATMs. Interestingly; LP partially reversed the increment of IL-6 in offspring fed with HE diet. Two-way ANOVA showed an interaction of prenatal LP and postnatal HE on IL-6 and IL-1 beta transcription. Overall, both LP and HE diets impact ATM phenotype by affecting the ratio of CD11c+CD206+ ATMs and the expression of IL-6.