Effects And Mechanisms Of Long Term Exercise Training/mitoQ Drinking In Low Birth Weight And Catch Up Growth Mice

Low birth weight(LBW) and catch up growth(CUG), are independent risk factors for the development of obesity and diabetes during adult life. Nutrition malnutrition followed by rapid ascension can lead to catch-up growth, and detrimental effects of low birth weight are amplified by rapid postnatal catch up growth.?Objectives?Investigate the effects and mechanisms of long term exercise training/mito Q drinking in low birth weight and catch up growth mice.?Methods?1?Mouse models were created by restricting maternal food intake during the last week of gestation. After weaning, normal birth weight mice(NBW) and low birth weight mice(LBW) were further distributed into four groups respectively: normal birth weight and normal chow(NBW-NFD), normal birth weight and high fat diet(NBW-HFD), normal birth weight and high fat diet with exercise training(NBW-HFD Ex), normal birth weight and high fat diet with mito Q drinking(NBW-HFD mito Q); low birth weight and normal chow(LBW-NFD), low birth weight and high fat diet(LBW-HFD), low birth weight and high fat diet with exercise training(LBW-HFD Ex), low birth weight and high fat diet with mito Q drinking(LBW-HFD mito Q).2?The critical growth period were assessed by recording body weight and calculating growth rate, energy intake and body composition were used to evaluate the obesity of mice, glucose tolerance and insulin sensitivity were evaluated using intra-peritoneal glucose tolerance test(IPGTT), insulin tolerance test(ITT).3?Mitochondrial function of skeletal muscle was assessed by ATP(Adenosine Triphosphate)Assay Kit, lipid oxidation of skeletal muscle was assessed by Lipid Peroxidation MDA(Malondialdehyde)Assay Kit, lipid deposition of skeletal muscle was assessed by Oil red O staining.4?The expression of genes at mRNA/DNA and protein levels were analyzed by quantitative real-time polymerase chain reaction(q RT-PCR) and Western blot respectively, which related to mitochondrial biogenesis, mitochondrial respiratory chain, anti-oxidative stress, endogenous antioxidant and fatty acid ?-oxidation.?Results?1?Low birth weight and catch up growth mice developed the most serious obesity and metabolic disorders in the 25 th week. The growth rate in the 4th week(GR4) of C57 BL /6J mice was significantly correlated with adult obesity.2?After long term exercise training in low birth weight and catch up growth mice,(1) GR4 and adult obesity were significantly reduced.(2) Area under the curve of IPGTT and ITT were significantly reduced.(3) Levels of ATP in skeletal muscle were significantly increased, while MDA levels were decreased significantly.(4) The expression of mitochondrial respiratory chain Complex I, mitochondrial fusion protein OPA-1 and Mfn2, mitochondrial synthesis related protein PGC-1?, anti-oxidative stress related protein Nrf2 and endogenous antioxidant catalase and Mn SOD in skeletal muscle were significantly increased. There were no differences in the expression of mitochondrial fission protein DRP-1.(5) mRNA levels of mitochondria synthesis related gene PGC-1?, Nrf1, Tfam and mitochondrial DNA levels in skeletal muscle were increased significantly.3?After long term mito Q drinking in low birth weight and catch up growth mice,(1) GR4 and adult obesity were significantly reduced.(2) Area under the curve of IPGTT and ITT were significantly reduced.(3) Levels of ATP in skeletal muscle were increased significantly, while MDA levels and lipids deposition in skeletal muscle were significantly decreased.(4) The expression of mitochondrial respiratory skeletal chain Complex I, mitochondrial fusion protein OPA-1, mitochondrial synthesis related protein PGC-1?, anti-oxidative stress related protein Nrf2 and endogenous antioxidant catalase and Mn SOD in skeletal muscle were significantly increased. There were no differences in the expression of mitochondrial fission protein DRP-1.(5) m RNA levels of mitochondria synthesis related gene PGC-1?, Nrf1, Tfam and mitochondrial fatty acid ?-oxidation related genes PPAR??CPT-1in skeletal muscle, and mitochondrial DNA levels in skeletal muscle were increased significantly.?Conclusions?1?There are two critical growth phases in C57 BL /6J mice: GR1-3 and GR4-7. The peak is GR1 and GR4, respectively.2?Long-term exercise training limited catch up growth and ameliorated metabolic disorders in adult of low birth weight mice, with increasing mitochondrial function and enhancing oxidative capacity in skeletal muscle.3?Long-term mito Q drinking limited catch up growth and ameliorated metabolic disorder in adult of low birth weight mice, with increasing mitochondrial fatty acid ?-oxidation and enhancing oxidative capacity in skeletal muscle.4?Mito Q is a potential pharmacy to treat catch up growth related metabolic disorders.