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Mireille van Poppel, PhD:

Physical activity and inflammation in pregnancy

Institute of Sport Science, University of Graz, Mozartgasse 14, A-8010 Graz;
phone: +43-316-380 2335, fax: +43-316-380 9097, ✉ e-mail
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Keywords:

Inflammation, lifestyle, obesity, cytokines, gestational diabetes, multilevel regression analyses, neonatal body composition

Research interest:

Physical activity (PA) has been shown to affect circulating cytokine levels. In trained individuals, reduced levels of pro-inflammatory cytokines are paralleled by an increase of anti-inflammatory cytokines (1). In addition, our group showed previously that maternal PA has an effect on a number of circulating cytokines in pregnancy, including interleukin (IL)-6 and tumor necrosis factor (TNF)-α (2).

These two cytokines (TNF-α and IL-6) are associated with glucose and insulin metabolism in pregnancy. TNF-α is consistently elevated in GDM (3), and is an independent predictor of insulin resistance in GDM (4). TNF-α has been hypothesized to exert an inhibitory effect on insulin secretion and insulin-regulated glucose uptake in GDM, thus contributing to the sustained hyperglycemia (5). IL-6 is elevated in women, who develop GDM (6) and our group showed that IL-6 is related to insulin sensitivity and insulin response in obese pregnant women (2).

Not only glucose metabolism, but also lipids are associated with cytokines in pregnancy. The group of G. Desoye showed that pro-inflammatory cytokines increase lipase expression and hence free fatty acid availability for transfer to the fetus (7). Low grade inflammation — through cytokines — changes maternal lipids, predominantly triglycerides and free fatty acids, and is related to fetal growth and adiposity (8). It has been postulated that inflammation, mostly IL-6, also influences fetal lipid availability independent of maternal lipids (9). Cytokines, such as IL-6 and TNF-α, modulate free fatty acid availability and thereby can affect fetal growth and body composition.

We hypothesize that physical activity will lead to different maternal and fetal cytokine levels and, through this, change glucose, triglyceride and free fatty acid levels. This will result in changes in fetal growth and neonatal body composition. We will analyze cytokine profiles in obese pregnant women and relate this to physical activity levels and maternal and neonatal outcomes.

Illustrations:

Fig. 1: Cytokine levels (box-whiskers plots) at all time periods in gestation for women with low (N = 19; open boxes) or high (N = 23; hatched boxes) MVPA at 15 weeks of gestation. P values between high- and low MVPA groups (Mann-Whitney U test) are indicated whenever significant. [2].

References:

  1. Teixeira-Lemos E, Nunes S, Teixeira F, Reis F: Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovasc Diabetol, 2011; 10:12.
  2. van Poppel MN, Peinhaupt M, Eekhoff ME, Heinemann A, Oostdam N, Wouters MG, van Mechelen W, Desoye G: Physical activity in overweight and obese pregnant women is associated with higher levels of proinflammatory cytokines and with reduced insulin response through interleukin-6. Diabetes Care, 2014; 37(4):​1132–1139.
  3. Xu J, Zhao YH, Chen YP, Yuan XL, Wang J, Zhu H, Lu CM: Maternal circulating concentrations of tumor necrosis factor-alpha, leptin, and adiponectin in gestational diabetes mellitus: a systematic review and meta-analysis. ScientificWorldJournal, 2014; 926932.
  4. Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM: TNF-α is a predictor of insulin resistance in human pregnancy. Diabetes, 2002; 51(7):​2207–2213.
  5. McLachlan KA, O'Neal D, Jenkins A, Alford FP: Do adiponectin, TNFα, leptin and CRP relate to insulin resistance in pregnancy? Studies in women with or without gestational diabetes, during and after pregnancy. Diabetes Metab Res Rev, 2006; 22(2):​131–138.
  6. Pantham P, Aye IL, Powell TL: Inflammation in maternal obesity and gestational diabetes mellitus. Placenta, 2015; 36(7):​709–715.
  7. Gauster M, Hiden U, van Poppel M, Frank S, Wadsack C, Hauguel-de Mouzon S, Desoye G: Dysregulation of placental endothelial lipase in obese women with gestational diabetes mellitus. Diabetes, 2011; 60(10):​2457–2464.
  8. Jawerbaum A, González E: Diabetic pregnancies: the challenge of developing in a pro-inflammatory environment. Curr–Med Chem, 2006; 13(18):​2127–2138.
  9. Catalano PM, Hauguel-De Mouzon S: Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic? . Am J  Obstet Gynecol, 2011; 204(6):​479–487.

Collaborations within the DP-iDP:

  • Á. Heinemann will support students in leukocyte adhesion- and activation assays.
  • G. Desoye will teach the students how to isolate endothelial cells and macrophages from the placenta and/or umbilical cord, introduce them to the biology of angiogenesis and help with assays of 2-D network formation and tube formation.
  • G. Marsche will supervise the studies addressing lipid metabolism of placental macrophages.
  • C. Wadsack will provide clinically well-defined placenta samples and help the students with ex vivo placenta perfusion assays.

Collaborating research groups where PhD students could perform their research stay abroad:

  • T. Roseboom (Amsterdam Medical Center, Amsterdam, the Netherlands) is an expert in developmental programming and will train the students in effects of the early life experiences on long-term health outcomes, using unique data from the Dutch famine.
  • E. Watson (Witsrand University, Johannesburg, South Africa) is an expert in physical activity in pregnancy research and will train the students in how to measure physical activity and fitness in pregnant women. Furthermore, students will experience the specific context in South Africa, putting lifestyle (changes) and prenatal health care in a different perspective .

Know-how and infrastructure of the research group:

The group of Mireille van Poppel is a recently established group with expertise on physical activity in pregnancy in relation to maternal and neonatal outcomes. Currently, studies are carried out to establish the validity of objective and self-reported measurement instruments of physical activity in pregnancy. The group comprises one post-doctoral fellow, one technician and two PhD students. The group has extensive expertise in epidemiology, statistical analyses and intervention research. These methodologies have been applied to research on lifestyle in pregnancy, specifically in relation to inflammation and metabolic outcomes. The group has access to devices for objective measurement of physical activity (accelerometers) and a physiology laboratory, for measuring physical fitness and energy expenditure.

Scientific concepts and techniques that students will learn in this laboratory:

DP-iDP students will be learning to take step back from cells and tissues, and consider the role of maternal characteristics during pregnancy (obesity, lifestyle, mental health) for inflammatory and metabolic outcomes. Basic concepts such as confounding, representativeness, bias, validity and causality will be trained, as well as other relevant epidemiological methods. Students will learn how to analyze clustered datasets (e. g. more than one cell culture isolated from one placenta, multiple measurements within one person) using multilevel analyses. They will make their own statistical analysis plan, using their own research design and outcome variables. All methods and analyses will be trained using data from studies within the topic of inflammation in pregnancy.

30.10.2016 DP-iDP Doctoral Programme “Inflammatory Disorders in Pregnancy”