Beneficial effects of exercise on offspring obesity and insulin resistance are reduced by maternal high-fat diet

Abstract

ScopeWe investigated the long-term effects of maternal high-fat consumption and post-weaning exercise on offspring obesity susceptibility and insulin resistance.MethodsC57BL/6J dams were fed either a high-fat (HFD, 40% kcal fat) or low-fat (LFD, 10% kcal fat) semi-synthetic diet during pregnancy and lactation. After weaning, male offspring of both maternal diet groups (mLFD; mHFD) received a LFD. At week 7, half of the mice got access to a running wheel (+RW) as voluntary exercise training. To induce obesity, all offspring groups (mLFD +/-RW and mHFD +/-RW) received HFD from week 15 until week 25.ResultsCompared to mLFD, mHFD offspring were more prone to HFD-induced body fat gain and exhibited an increased liver mass which was not due to increased hepatic triglyceride levels. RW improved the endurance capacity in mLFD, but not in mHFD offspring. Additionally, mHFD offspring +RW exhibited higher plasma insulin levels during glucose tolerance test and an elevated basal pancreatic insulin production compared to mLFD offspring.ConclusionTaken together, maternal HFD reduced offspring responsiveness to the beneficial effects of voluntary exercise training regarding the improvement of endurance capacity, reduction of fat mass gain, and amelioration of HFD-induced insulin resistance.

Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice

“…This resulted in a significantly improved endurance exercise capacity which was 2.7 fold increased by VWR by week 15 (Fig. 1e) confirming previous data obtained with a comparable study setup 19,20 . Skeletal muscle citrate synthase (CS) activity as a marker for mitochondria content was not changed by VWR (Fig.…”

“…Three separate experiments were performed using male C57Bl/6J mice bred in house that were single caged and kept in a light- and temperature-controlled facility at 22 °C with a 12 h light-12 h dark cycle and food and water ad libitum. The experimental setup of the first two experiments was based on previous studies where we investigated exercise adaptation in the context of maternal programming by high fat diets 19,20,47 . Male mice were fed semisynthetic diets throughout their life and were born from dams that were already fed the same respective diet.…”

“…Daily wheel running use was recorded using TSE Systems GmbH (Homburg, Germany). Endurance performance (exercise capacity) was determined by forced treadmill exercise until exhaustion using a six-lane treadmill (Columbus Instruments, Columbus, USA) as described previously 19 . Exercise capacity is indicated as the average treadmill running distance (m) until exhaustion.…”

“…Muscle citrate synthase activity was measured as previously described 19,50 . Plasma creatine kinase and lactate were measured using an automated analyzer (Cobas Mira S, Hoffmann-La Roche, Basel, Switzerland).…”

“…For that, we made use of voluntary wheel running (VWR) as an active lifestyle mimic in lean and obese mice. VWR enhances exercise capacity in mice 19,20 and prolongs health-span by preventing the age-related decline of aerobic fitness and motor coordination 21 . Here we investigated the acute skeletal muscle transcriptional response to an exhaustive exercise bout in sedentary and active mice, and the effect of VWR on circulating GDF15.…”