Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism

Abstract

BACKGROUNDMaternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO.HYPOTHESISMO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx prevents these outcomes.METHODSF0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day ninety of life through pregnancy beginning day 120) providing four groups (n=8/group) – i) controls, ii) obese, iii) exercised controls and iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed.RESULTSExercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially glucose, insulin, cholesterol and oxidative stress increases. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 Offspring weights were similar at birth. At PND 36 MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise.CONCLUSIONSMEx before and during pregnancy has beneficial effects on maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status.

Homage to the ‘H’ in developmental origins of health and disease

“…However, male offspring from exercised, obese dams showed reduced glucose concentrations Maternal exercise did not impact blood glucose concentrations in female pups Insulin concentrations were reduced in male pups from exercised lean and obese dams Female pups from obese, non-exercised dams were significantly increased, and maternal exercise did not alter insulin concentrations in female offspring Plasma triglycerides were lower in male pups from lean exercised dams but increased in those from obese exercised dams Glut4 (glucose transporter) and Myod1 (moygenesis-related gene) was downregulated in male offspring from non-exercised, obese dams but normalized in those from exercised, obese dams. Pgc1α, a transcriptional co-activator regulating many genes involved in energy metabolism, was upregulated in male offspring from exercised dams Glut4 and Pgc1a were upregulated in retroperitoneal white adipose tissue (WAT) of male and female offspring from lean but not obese exercised dams Tnf-α (a marker of inflammation) was elevated in male pups from both lean and obese exercised dams but in females, this gene was only increased in lean exercised dams Il6, another inflammatory marker, was elevated in male pups from lean and to a lesser extent obese exercised dams 37 Female Sprague Dawley rats Maternal exercise (voluntary wheel running) before mating and throughout pregnancy and lactation Female offspring of exercised dams displayed enhanced glucose turnover during glucose tolerance testing, increased glucose infusion rates, and whole body glucose turnover rates during hyperinsulinemic-euglycemic clamp testing Female offspring from exercised dams had decreased insulin levels and hepatic glucose production during the clamp procedure Insulin infusion resulted in increased glucose uptake in skeletal muscle and decreased heart glucose uptake in offspring of exercised dams 38 Male and female Wistar Albino rats Maternal exercise before mating and throughout gestation for control and obese dams Serum corticosterone was increased in neonatal offspring of non-exercised obese dams but decreased in offspring from exercised control and obese dams Insulin was increased in male offspring of non-exercised obese dams Leptin and triglycerides were increased in male offspring of obese non-exercised dams but leptin and partially triglycerides were reduced in those from obese exercised dams Glucose and homeostasis model assessment (HOMA), calculated from HOMA = glucose (mmol/l) × insulin (μU/ml), were decreased in male and female offspring of control exercised dams 39 Male and female Wistar rats Maternal exercise 5 days before breeding and throughout pregnancy…”

“…34 Several rodent studies indicate that maternal exercise before and/or during gestation improves glucose homeostasis, 35,36 and insulin sensitivity 36 and decreases leptin concentrations in offspring. 37 Long lasting changes in the musculoskeletal system and adiposity are observed in Wistar rat offspring, especially in males, of exercised dams. 38 Such changes include lower bone mineral density, increase circulating concentrations of undercarboxylated osteocalcin and greater percentage of total fat but lower percentage of lean fat compared with controls.…”

Accelerated aging of reproductive capacity in male rat offspring of protein-restricted mothers is associated with increased testicular and sperm oxidative stress

“…All samples were read in a plate at 532 nm in a PerkinElmer LS50-B luminescence spectrometer. Results were expressed as nanomole MDA per milligram of protein or nmol MDA per 5 x 10 6 sperm (Vega et al 2013). Intra-and inter-assay coefficients of variation were <6 and <8 %, respectively.…”

“…At the end of the incubation period, fluorescent signals at an excitation wavelength of 488 nm and an emission wavelength of 525 nm were recorded in a PerkinElmer LS50-B luminescence spectrometer. Results were expressed as nanomoles of DCF formed per milligram of protein per minute or DCF formed per 5 x 10 6 sperm per minute (Vega et al 2013). …”

Optimizing Pregnancy for Intergenerational Health Benefits

“…Controlled experiments of maternal PA in animal models has shown beneficial impact on many offspring variables; hippocampal neurons and angiogenesis [53], insulin sensitivity [54,55] and metabolism [56], expression of molecules known to attenuate placental dysfunction [57], high fat diet induced changes in metabolic regulator genes [58], as well as hippocampal neurogenesis, learning, and memory [59]. Thus, it is not unrealistic to presume that PA behaviors, affecting maternal metabolism and the metabolic milieu, could affect fetal body composition and downstream health.…”