Biology subjects

Kral, J. G.

Publications and source records attributed to Kral, J. G..

3 recordsLinked to original sources

bioRxiv2018

Epigenetic transmission of cardiometabolic risk in offspring discordant for maternal gestational metabolic fitness

OBJECTIVEDiabesity during gestation predisposes offspring to lifetime cardiometabolic risk. We demonstrated that maternal biliopancreatic diversion surgery (BPD) improved metabolic fitness and pregnancies reducing cardiometabolic risk in siblings born after (AMS) compared to before maternal surgery (BMS). We found differential methylation of inflammatory and glucoregulatory genes in peripheral blood cell DNA in offspring and in mothers after BPD compared to preoperative \"control\" women. Here we study offspring trajectories of cardiometabolic risk markers and determine persistence of the methylome related to body weight (BMI) and gestational weight gain (GWG).\n\nRESEARCH DESIGN AND METHODSProspective, cross-sectional study of 133 mothers with 89 BMS and 183 AMS offspring born mean 4 years after BPD and 83 unoperated control women was conducted, and differential methylation patterns in mothers were compared with those of offspring during 2-26 years.\n\nRESULTSIndependent of maternal or offspring BMI and GWG, postoperative maternal metabolic fitness was associated with improved cardiometabolic phenotype in AMS vs. BMS offspring sustained beyond puberty. BMS offspring exhibited increasing linear trajectories of weight, cardiometabolic and inflammation risk factors versus normative horizontal trajectories of AMS offspring. Methylation differences between AMS and BMS offspring identified 45 625 differentially methylated sites, 73% overlapping with those of mothers vs. controls; 4 446 demonstrated similar sustained directionality of differences in methylation levels; 154 sites exhibited significant correlation coefficients (r[≥]0.4) overrepresented within genes associated with cardiometabolic risk, growth and inflammation.\n\nCONCLUSIONMaternal BPD appears to epigenetically prevent transmission of cardiometabolic risk independent of BMI.

developmental biology↗

bioRxiv2017

Paternal grandparental exposure to crop failure or surfeit during a childhood slow growth period and epigenetic marks on third generational growth-, glucoregulatory and stress genes

This latest in our series of papers describes transgenerational methylation related to midchildhood food availability in 19th century Overkalix, Sweden. Failed vs. bountiful crops differentially influenced methylation in grandchildren of paternal grandparents exposed to feast or famine during their Slow Growth Period (SGP), a sensitive period preceding the pre-pubertal growth spurt. In this case-study of 8 tracked 75-year old progeny with differential ancestral exposure, we found, in 40 posited gene ontology pathways, 39 differentially methylated CpG regions (DMRs) related to famine, excess food and food-insecurity stress, 9 of which with DMRs above 5%. Three gene ontology terms (GOs) \"insulin processing\", \"adipose development\" and \"hypothalamus development\" were key, with DMRs >14%. An unbiased test of known pathways revealed four nuclear transcription factors upstream of promotors repressing the pathway following paternal grandparental famine experience, as well as 4 upregulated GOs with average DMRs >20%. We conclude that this is the first demonstration of human transgenerational inheritance of epigenetic marks following ancestral childhood exposure to variable food availability inducing early developmental origins of adult disease.

genomics↗

bioRxiv2017

Cardio- and neurometabolic effects of lower-body pressure supported exercise in obese non-diabetic women: Resetting autonomic imbalance?

BackgroundOvernutrition and underactivity cause most chronic disease via inflammation and stress. Life-style changes such as diet is largely unsuccessful and exercise is painful, uncomfortable and difficult for people with diabesity, cardiorespiratory and joint diseases and cognitive decline affecting their ability to ambulate and adhere to exercise guidelines. Diets or exercise causing weight loss are stressful and trigger numerous redundant counter regulatory mechanisms defending lean body mass, explaining failures to sustain these behaviors. In this hypothesis-generating pilot study we used a NASA-developed weight supporting lower-body positive pressure (LBPP) treadmill providing comfortable low-amount, low intensity walking, challenging current exercise guidelines.\n\nMethodsSixteen nondiabetic, untrained, Black volunteer women (BMI 28-50), age 18-56 years were studied by anthropometry, analyses of energy expenditure and blood chemistry: oral glucose tolerance tests (OGTT) with insulin, C-peptide, GLP-1 and FFA and fasting lipids, cytokines, adipokines and appetitive peptides, before and after 10 weeks of twice weekly 30-minute weight supported LBPP treadmill sessions.\n\nResultsWe found novel baseline associations between gluco- and neuro-regulatory peptides and plasma lipids, inflammatory cytokines and appetitive hormones related to neurogenesis, mood and energy balance. Post-study, independent of body weight or energy expended there were significant decreases in OGTT plasma insulin (p=0.002) and GLP-1 (p=0.060) and fasting triglycerides (p=0.029), ghrelin (p=0.008) and changes in most molecules including increased leptin and beta-endorphin. Correlations between changes among different classes of peptides were highly significant, notably leptin - adiponectin, and beta-endorphin - oxytocin and orexin A. We propose synergy between low-amount, low-intensity exercise at levels below thresholds of increased sympathetic tone, and baro-physiological effects of LBPP normalizing parasympathetic tone.\n\nConclusionBrief, low-dose, lower-body positive-pressure weight-supported treadmill exercise improved cardiometabolic fitness and exhibited favorable changes in neuro-regulatory peptides without weight loss in inner-city obese Black women.

physiology↗