Early life undernutrition reduces maximum treadmill running capacity in adulthood in mice.

Introduction: Undernutrition during early life causes chronic disease with specific impairments to the heart and skeletal muscle. Purpose: To determine the effects of early-life undernutrition on adult exercise capacity as a result of cardiac and skeletal muscle function. Methods: Pups were undernourished during gestation (GUN) or lactation (PUN) using a cross-fostering nutritive mouse model. At postnatal day 21 (PN21), all mice were weaned and refed a control diet. At PN67, mice performed a maximal treadmill test. Echocardiography and Doppler blood flow analysis was performed at PN72, following which skeletal muscle cross-sectional area (CSA) and fiber type were determined. Results: Maximal running capacity was reduced (Diet: P=0.0002) in GUN and PUN mice. Left ventricular mass (Diet: P=0.03) and posterior wall thickness during systole (Diet*Sex: P=0.03) of GUN and PUN mice was reduced, causing PUN mice to have reduced (Diet: P=0.04) stroke volume (SV). Heart Rate (HR) of GUN mice showed a trend (Diet: P=0.07) towards greater resting values than other groups. PUN mice had greater CSA of SOL fibers. PUN had a reduced (Diet: P=0.03) proportion of type-IIX fibers in the EDL and a greater (Diet: P=0.008) percentage of type-IIB fibers in the EDL. Conclusion: Gestational and Postnatal undernourishment impairs exercise capacity.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Isolation, expression analysis and characterization of NEFA-interacting nuclear protein 30 and RING finger and SPRY domain containing 1 in skeletal muscle

Muscle atrophy results from a range of physiological conditions, including immobilization, spinal cord damage, inflammation and aging. In this study we describe two genes, NEFA-interacting nuclear protein 30 (Nip30) and RING Finger and SPRY domain containing 1 (Rspry1), which have not previously been characterized or shown to be expressed in skeletal muscle. Furthermore, Nip30 and Rspry1 were transcriptionally induced in response to neurogenic muscle wasting in mice and were also found to be expressed endogenously at the RNA and protein level in C2C12 mouse muscle cells. Interestingly, during analysis of Nip30 and Rspry1 it was observed that these genes share a 230 base pair common regulatory region that contains several putative transcription regulatory elements. In order to assess the transcriptional activity of the Nip30 and Rspry1 regulatory regions, a fragment of the promoter of each gene was cloned, fused to a reporter gene, and transfected into cells. The Nip30 and Rspry1 reporters were both found to have significant transcriptional activity in cultured cells. Furthermore, the Nip30-Rspry1 common regulatory region contains a conserved E-box enhancer, which is an element bound by myogenic regulatory factors that function in the regulation of muscle-specific gene expression. Therefore, in order to determine if the predicted E-box was functional, Nip30 and Rspry1 reporters were transfected into cells ectopically expressing the myogenic regulatory factor, MyoD1, resulting in significant induction of both reporter genes. In addition, mutation of the conserved E-box element eliminated MyoD1 activation of the Nip30 and Rspry1 reporters. Finally, GFP-tagged Nip30 was found to localize to the nucleus, while GFP-tagged Rspry1 was found to localize to the cytoplasm of muscle cells

Quercetin's Influence on Exercise Performance and Muscle Mitochondrial Biogenesis

ABSTRACT Purpose: To determine the influence of 2 wk of quercetin (Q; 1000 mg·d Methods: Using a randomized, crossover design with a 2-wk washout period, subjects provided blood and muscle biopsy samples presupplementation and postsupplementation periods and were given 12-min time trials on 15% graded treadmills after 60 min of moderate exercise preloads at 60% V·O 2max . Results: Plasma Q levels rose significantly in Q versus P during the 2-wk supplementation period (interaction P value <0.001). During the 12-min trial, the net change in distance achieved was significantly greater during Q (2.9%) compared with P (-1.2%; 29.5 ± 11.5 vs -11.9 ± 16.0 m, respectively, P = 0.038). Skeletal muscle messenger RNA expression tended to increase (range = 16-25%) during Q versus P for sirtuin 1 (interaction effect, P = 0.152), peroxisome proliferator-activated receptor [gamma] coactivator-1[alpha] (P = 0.192), cytochrome c oxidase (P = 0.081), and citrate synthase (P = 0.166). Muscle mitochondrial DNA (relative copy number per diploid nuclear genome) increased 140 ± 154 (4.1%) with Q compared with -225 ± 157 (6.0% decrease) with P (P = 0.098). Conclusions: In summary, 1000 mg·d -1 Q versus P for 2 wk by untrained males was associated with a small but significant improvement in 12-min treadmill time trial performance and modest but insignificant increases in the relative copy number of mitochondrial DNA and messenger RNA levels of four genes related to mitochondrial biogenesis

Early probiotic supplementation and the risk of celiac disease in children at genetic risk

Abstract Probiotics are linked to positive regulatory effects on the immune system. The aim of the study was to examine the association between the exposure of probiotics via dietary supplements or via infant formula by the age of 1 year and the development of celiac disease autoimmunity (CDA) and celiac disease among a cohort of 6520 genetically susceptible children. Use of probiotics during the first year of life was reported by 1460 children. Time-to-event analysis was used to examine the associations. Overall exposure of probiotics during the first year of life was not associated with either CDA (n = 1212) (HR 1.15; 95%CI 0.99, 1.35; p = 0.07) or celiac disease (n = 455) (HR 1.11; 95%CI 0.86, 1.43; p = 0.43) when adjusting for known risk factors. Intake of probiotic dietary supplements, however, was associated with a slightly increased risk of CDA (HR 1.18; 95%CI 1.00, 1.40; p = 0.043) compared to children who did not get probiotics. It was concluded that the overall exposure of probiotics during the first year of life was not associated with CDA or celiac disease in children at genetic risk