Effects of exercise and diet interventions on obesity-related sleep disorders in men: study protocol for a randomized controlled trial.
Abstract Background Sleep is essential for normal and healthy living. Lack of good quality sleep affects physical, mental and emotional functions. Currently, the treatments of obesity-related sleep disorders focus more on suppressing sleep-related symptoms pharmaceutically and are often accompanied by side effects. Thus, there is urgent need for alternative ways to combat chronic sleep disorders. This study will investigate underlying mechanisms of the effects of exercise and diet intervention on obesity-related sleep disorders, the role of gut microbiota in relation to poor quality of sleep and day-time sleepiness, as well as the levels of hormones responsible for sleep-wake cycle regulati…
Branched-Chain Amino Acid Deprivation Decreases Lipid Oxidation and Lipogenesis in C2C12 Myotubes
Impaired lipid metabolism is a common risk factor underlying several metabolic diseases such as metabolic syndrome and type 2 diabetes. Branched-chain amino acids (BCAAs) that include valine, leucine and isoleucine have been proven to share a role in lipid metabolism and hence in maintaining metabolic health. We have previously introduced a hypothesis suggesting that BCAA degradation mechanistically connects to lipid oxidation and storage in skeletal muscle. To test our hypothesis, the present study examined the effects of BCAA deprivation and supplementation on lipid oxidation, lipogenesis and lipid droplet characteristics in murine C2C12 myotubes. In addition, the role of myotube contract…
Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats
Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having onl…
Serum osteocalcin is not associated with glucose but is inversely associated with leptin across generations of nondiabetic women.
The skeleton is recognized as an important player in energy metabolism through its interactions with other tissues. Whether the association of osteocalcin with glucose metabolism is age dependent has not been fully addressed.The objective of the study was to examine the age-specific association between different forms of osteocalcin and glucose and adipokines.This was a family-based study across three generations.The study was conducted at a university laboratory.Sixty-four daughter-premenopausal mother-maternal grandmother trios participated in the study.Fasting plasma glucose and insulin concentrations, serum total (tOC), carboxylated (cOC), and uncarboxylated (ucOC = tOC - cOC) osteocalc…
Suoliston mikrobit ja fyysinen suorituskyky
Suolistoamme asuttava miljardilukuinen mikrobiyhteisö osallistuu fysiologiaamme monin tavoin. Se kykenee esimerkiksi hajottamaan ravinnosta yhdisteitä, joihin omat entsyymimme eivät pure. Poikittaistutkimuksissa on löydetty ihmisen fyysisen suorituskyvyn ja suolistomikrobien välisiä yhteyksiä. Liikunta-aktiivisuus näyttäisi lisäävän tiettyjen terveysvaikutteisten suolistomikrobien määrää. Pitkittäistutkimuksista tekemämme systemoitu katsaus osoittaa, että liikunta vaikuttaa ihmisten suolistomikrobeihin, mutta tulokset ovat ristiriitaisia. Yleisimmin keskikuormittava kestävyysliikunta on aiheuttanut eniten muutoksia suolistossa, mutta tähänastinen tutkimus on painottunut iäkkäisiin, ylipaino…
Gut Microbiota and Serum Metabolome in Elite Cross-Country Skiers : A Controlled Study
Exercise has been shown to affect gut the microbiome and metabolic health, with athletes typically displaying a higher microbial diversity. However, research on the gut microbiota and systemic metabolism in elite athletes remains scarce. In this study, we compared the gut microbiota profiles and serum metabolome of national team cross-country skiers at the end of an exhausting training and competitive season to those of normally physically-active controls. The gut microbiota were analyzed using 16S rRNA amplicon sequencing. Serum metabolites were analyzed using nuclear magnetic resonance. Phylogenetic diversity and the abundance of several mucin-degrading gut microbial taxa, including Akker…
Are skeletal muscle FNDC5 expression and irisin release regulated by exercise and related to health?
Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n= 17), (2) a heavy-intensity resistance exercise (RE) bout (young n= 10, older n= 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n= 9), or (4) …
Aerobic exercise training and gut microbiome-associated metabolic shifts in women with overweight : a multi-omic study
Physical activity is essential in weight management, improves overall health, and mitigates obesity-related risk markers. Besides inducing changes in systemic metabolism, habitual exercise may improve gut’s microbial diversity and increase the abundance of beneficial taxa in a correlated fashion. Since there is a lack of integrative omics studies on exercise and overweight populations, we studied the metabolomes and gut microbiota associated with programmed exercise in obese individuals. We measured the serum and fecal metabolites of 17 adult women with overweight during a 6-week endurance exercise program. Further, we integrated the exercise-responsive metabolites with variations in the gu…
Women With and Without Metabolic Disorder Differ in Their Gut Microbiota Composition
The aim of this study was to investigate whether overweight/obese women in metabolic disorder group (MDG, n = 27) differ in their gut microbiota composition from overweight/obese women in non-metabolic disorder group (NMDG, n = 47) and normal weight women group (NWG, n = 11). Gut microbiota was profiled from fecal samples by 16S rRNA fluorescence in situ hybridization and flow cytometry in 85 premenopausal women. Body composition was measured by bioimpedance, and dietary intakes were collected via food diaries. Standard procedures were used to assess plasma glucose, serum insulin, lipids, and inflammatory status. We found that the proportion of bacteria belonging to Eubacterium rectale-Clos…
Gut Microbiota Analysis Results Are Highly Dependent on the 16S rRNA Gene Target Region, Whereas the Impact of DNA Extraction Is Minor
Next-generation sequencing (NGS) is currently the method of choice for analyzing gut microbiota composition. As gut microbiota composition is a potential future target for clinical diagnostics, it is of utmost importance to enhance and optimize the NGS analysis procedures. Here, we have analyzed the impact of DNA extraction and selected 16S rDNA primers on the gut microbiota NGS results. Bacterial DNA from frozen stool specimens was extracted with 5 commercially available DNA extraction kits. Special attention was paid to the semiautomated DNA extraction methods that could expedite the analysis procedure, thus being especially suitable for clinical settings. The microbial composition was an…
Faecalibacterium prausnitzii treatment improves hepatic health and reduces adipose tissue inflammation in high-fat fed mice
Faecalibacterium prausnitzii is considered as one of the most important bacterial indicators of a healthy gut. We studied the effects of oral F. prausnitzii treatment on high-fat fed mice. Compared to the high-fat control mice, F. prausnitzii-treated mice had lower hepatic fat content, aspartate aminotransferase and alanine aminotransferase, and increased fatty acid oxidation and adiponectin signaling in liver. Hepatic lipidomic analyses revealed decreases in several species of triacylglycerols, phospholipids and cholesteryl esters. Adiponectin expression was increased in the visceral adipose tissue, and the subcutaneous and visceral adipose tissues were more insulin sensitive and less infl…
Enterobacter cloacae administration induces hepatic damage and subcutaneous fat accumulation in high-fat diet fed mice.
Accumulating evidence indicates that gut microbiota plays a significant role in obesity, insulin resistance and associated liver disorders. Family Enterobacteriaceae and especially Enterobacter cloacae strain B29 have been previously linked to obesity and hepatic damage. The underlying mechanisms, however, remain unclear. Therefore, we comprehensively examined the effects of E. cloacae subsp. cloacae (ATCC® 13047™) administration on host metabolism of mice fed with high-fat diet (HFD). C57BL/6N mice were randomly divided into HFD control, chow control, and E. cloacae treatment groups. The E. cloacae treatment group received live bacterial cells in PBS intragastrically twice a week, every ot…
PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise
The primary aim of the present study was to investigate the acute gene expression responses of PGC-1 isoforms and PGC-1a target genes related to mitochondrial biogenesis (cytochrome C), angiogenesis (VEGF-A), and muscle hypertrophy (myostatin), after a resistance or endurance exercise bout. In addition, the study aimed to elucidate whether the expression changes of studied transcripts were linked to phosphorylation of AMPK and MAPK p38. Nineteen physically active men were divided into resistance exercise (RE, n = 11) and endurance exercise (EE, n = 8) groups. RE group performed leg press exercise (10 9 10 RM, 50 min) and EE walked on a treadmill (~80% HRmax, 50 min). Muscle biopsies were ob…
Effect of aerobic exercise and low carbohydrate diet on pre-diabetic non-alcoholic fatty liver disease in postmenopausal women and middle aged men - the role of gut microbiota composition
Background Pre-diabetes and non-alcoholic fatty liver disease (NAFLD) are associated with an unhealthy lifestyle and pose extremely high costs to the healthcare system. In this study, we aim to explore whether individualized aerobic exercise (AEx) and low carbohydrate diet (LCh) intervention affect hepatic fat content (HFC) in pre-diabetes via modification of gut microbiota composition and other post-interventional effects. Methods/design A 6-month randomized intervention with 6-month follow-up is conducted from January 2013 to December 2015. The target sample size for intervention is 200 postmenopausal women and middle-aged men aged 50–65 year-old with pre-diabetes and NAFLD. The qualified…
Xylo-Oligosaccharides in Prevention of Hepatic Steatosis and Adipose Tissue Inflammation: Associating Taxonomic and Metabolomic Patterns in Fecal Microbiomes with Biclustering
We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms associated with these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12 weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a use…
The Microbiome Studies in Metabolic Diseases have Advanced but are Poorly Standardized and Lack a Mechanistic Perspective
Copyright: © 2014 Pekkala S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. During the last decades hundreds of studies have reported the association of Gut Microbiota (GM) with obesity and related metabolic disorders [1]. However, recently the microbiome studies were criticized about the lack of skepticism [2]. The author of the article questioned the role of GM in different diseases and asked whether the detected differences between the subjects biologically matter? We do believe that the role of…
Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women
AbstractInsulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain …
Six-Week Endurance Exercise Alters Gut Metagenome That Is not Reflected in Systemic Metabolism in Over-weight Women
Recent studies suggest that exercise alters the gut microbiome. We determined whether six-weeks endurance exercise, without changing diet, affected the gut metagenome and systemic metabolites of overweight women. Previously sedentary overweight women (n = 19) underwent a six-weeks endurance exercise intervention, but two were excluded due to antibiotic therapy. The gut microbiota composition and functions were analyzed by 16S rRNA gene amplicon sequencing and metagenomics. Body composition was analyzed with DXA X-ray densitometer and serum metabolomics with NMR metabolomics. Total energy and energy-yielding nutrient intakes were analyzed from food records using Micro-Nutrica software. Serum…
Adipocytes as a Link Between Gut Microbiota-Derived Flagellin and Hepatocyte Fat Accumulation
While the role of both elevated levels of circulating bacterial cell wall components and adipose tissue in hepatic fat accumulation has been recognized, it has not been considered that the bacterial components-recognizing adipose tissue receptors contribute to the hepatic fat content. In this study we found that the expression of adipose tissue bacterial flagellin (FLG)-recognizing Toll-like receptor (TLR) 5 associated with liver fat content (r = 0.699, p = 0.003) and insulin sensitivity (r = -0.529, p = 0.016) in humans (n = 23). No such associations were found for lipopolysaccharides (LPS)-recognizing TLR4. To study the underlying molecular mechanisms of these associations, human HepG2 he…
Intrinsic aerobic capacity governs the associations between gut microbiota composition and fat metabolism age-dependently in rat siblings
Host genetic factors affecting the gut microbiome play an important role in obesity, yet limited attention has been paid on the host genetic factors linked to physical fitness in modifying the microbiome. This study determined whether sibling-matched pairs of rats selectively bred for high (HCR) and low (LCR) aerobic capacity differ in their microbiome age-dependently and which taxa associate with differential in metabolism. Several taxa in young adult rats (hereafter young) linked to inherited aerobic capacity, while in older adult (hereafter old) rats most of the differences between the lines associated with body weight. Despite the absence of weight differential between LCR and HCR when…
Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling
Alongside in vivo models, a simpler and more mechanistic approach is required to study the effects of myostatin on skeletal muscle because myostatin is an important negative regulator of muscle size. In this study, myostatin was administered to murine (C2C12) and human (CHQ) myoblasts and myotubes. Canonical and noncanonical signaling downstream to myostatin, related ligands, and their receptor were analyzed. The effects of tumorkines were analyzed after coculture of C2C12 and colon cancer-C26 cells. The effects of myostatin on canonical and noncanonical signaling were strongly reduced in C2C12 cells after differentiation. This may be explained by increased follistatin, an endogenous blocke…
Metabolic response to 6-week aerobic exercise training and dieting in previously sedentary overweight and obese pre-menopausal women: A randomized trial
AbstractBackground: The aim of this study was to compare 6 weeks short-term moderate intensity aerobic exercise and dieting on serum metabolomicsand cardio-metabolic risk factors in pre-menopausal women.Methods: Ninety previously inactive overweight and obese (BMI 25e35 kg/m 2 ) women (age 41.5 7.6 years) were randomized to either a6-week Nordic walking exercise program (EX, n ¼ 45) or dietary counseling group (DI, n ¼ 45). Body composition, serum glucose, insulin andlipids were measured. Serum low-molecular-weight metabolites and lipid constituents were analyzed by nuclear magnetic resonance spec-troscopy. Measurements were done at baseline and 7 days after the last training session.Result…
Peritoneal Cavity is a Route for Gut-Derived Microbial Signals to Promote Autoimmunity in Non-Obese Diabetic Mice
Macrophages play a crucial role in innate immune reactions, and peritoneal macrophages (PMs) guard the sterility of this compartment mainly against microbial threat from the gut. Type 1 diabetes (T1D) is an autoimmune disease in which gut microbiota and gut immune system appear to contribute to disease pathogenesis. We have recently reported elevated free radical production and increased permeability of gut epithelium in non-obese diabetic (NOD) mice. Impaired barrier function could lead to bacterial leakage to the peritoneal cavity. To explore the consequences of impaired gut barrier function on extra-intestinal immune regulation, we characterized peritoneal lavage cells from young newly w…
Fecal Metagenomics and Metabolomics Identifying Microbial Signatures in Non-Alcoholic Fatty Liver Disease
The frequency of non-alcoholic fatty liver disease (NAFLD) has intensified, creating diagnostic challenges and increasing the need for reliable non-invasive diagnostic tools. Due to the importance of the gut–liver axis in the progression of NAFLD, studies attempt to reveal microbial signatures in NAFLD, evaluate them as diagnostic biomarkers, and to predict disease progression. The gut microbiome affects human physiology by processing the ingested food into bioactive metabolites. These molecules can penetrate the portal vein and the liver to promote or prevent hepatic fat accumulation. Here, the findings of human fecal metagenomic and metabolomic studies relating to NAFLD are reviewed. The …
Inflammatory Biomarkers in Elite Cross-Country Skiers After a Competition Season : A Case-Control Study
Abstract Purpose Whether elite athletes, who have been exposed to vigorous-intensity exercise combined with other stressors, have elevated systemic low-grade inflammation, remains largely unclear. To address this question, we studied the levels of six inflammatory cytokines as potential biomarkers of a low-grade inflammatory state in elite athletes after an 11-month training and competition season. Methods We collected sera from 27 Finnish elite cross-country skiers and 27 gender- and age-matched, moderately-exercising controls. The serum concentrations of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), glycoprotein acetyls (GlycA), interleukin 10 (IL-10…
Gut Microbiota, Microbial Metabolites and Human Physical Performance
Trillions of microbes inhabiting the gut modulate the metabolism of the host. Cross-sectional studies have reported associations between physical performance and the gut microbiota (GM). Physical activity seems to increase GM diversity and the abundance of certain health-beneficial microbes. We reviewed the evidence from longitudinal studies on the connection between physically active lifestyle or long-term exercise interventions and the GM. We made literature searches using databases of Web of Science and PubMed Medline to collect human studies showing or not the associations between the GM and exercise. Many controversies exist in the studies. However, the longitudinal studies show that f…
Are skeletal muscleFNDC5gene expression and irisin release regulated by exercise and related to health?
Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n = 17), (2) a heavy-intensity resistance exercise (RE) bout (young n = 10, older n = 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n = 9), or …
Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation
The application of exercise-like electrical pulse simulation (EL-EPS) has become a widely used exercise mimetic in vitro. EL-EPS produces similar physiological responses as in vivo exercise, while less is known about the detailed metabolic effects. Routinely, the C2C12 myotubes are cultured in high-glucose medium (4.5 g/L), which may alter EL-EPS responses. In this study, we evaluate the metabolic effects of EL-EPS under the high- and low-glucose (1.0 g/L) conditions to understand how substrate availability affects the myotube response to EL-EPS. The C2C12 myotube, media, and cell-free media metabolites were analyzed using untargeted nuclear magnetic resonance (NMR)-based metabolomics. Furt…
Exercise, the endocannabinoid system and metabolic health
As obesity and associated metabolic disorders, such as type 2 diabetes and dyslipidemia, are becoming one of the most serious health problems worldwide, development of effective therapies is a high priority. In the search for treatments, the recently discovered endocannabinoid system (ECS) has begun to garner attention, and a wealth of research is now focusing on this unique neuromodulatory system named after the plant that led to its discovery. The ECS consists of G protein-coupled cannabinoid receptors (CB1 and CB2), their endogenous lipid-derived ligands (endocannabinoids, N-arachidonoylethanolamine, named anandamide (AEA) and 2-arachidonoylglycerol (2-AG)) and the enzymes for ligand syn…
Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study
Nicotinamide adenine dinucleotide (NAD + ) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)–discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD + metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota compos…
Prebiotic Xylo-oligosaccharides Targeting Faecalibacterium prausnitzii Prevent High Fat Diet-induced Hepatic Steatosis in Rats
Understanding the importance of gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat associated with low abundance of Faecalibacterium prausnitzii in humans and further, administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed to target F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD) or low (LFD) fat-diet for 12-weeks in Wistar rats (n=10/group). XOS increased F. prausnitzii growth having only minor impact on the GM composition. When supp…
Six-Week Endurance Exercise Alters Gut Metagenome That Is not Reflected in Systemic Metabolism in Over-weight Women
Recent studies suggest that exercise alters the gut microbiome. We determined whether six-weeks endurance exercise, without changing diet, affected the gut metagenome and systemic metabolites of overweight women. Previously sedentary overweight women (n = 19) underwent a six-weeks endurance exercise intervention, but two were excluded due to antibiotic therapy. The gut microbiota composition and functions were analyzed by 16S rRNA gene amplicon sequencing and metagenomics. Body composition was analyzed with DXA X-ray densitometer and serum metabolomics with NMR metabolomics. Total energy and energy-yielding nutrient intakes were analyzed from food records using Micro-Nutrica software. Serum…
Does Systemic Low-Grade Inflammation Associate With Fat Accumulation and Distribution? A 7-Year Follow-Up Study With Peripubertal Girls
Knowledge about the interrelationship between adiposity and systemic low-grade inflammation during pubertal growth is important in detecting early signs of obesity-related metabolic disorders.The objective of the study was to evaluate the developmental trajectories of fat mass (FM) and high sensitive C-reactive protein (hsCRP) levels and factors that could explain the relationship between FM and hsCRP in girls from prepuberty to early adulthood.This was a 7.5-year longitudinal study.The study was conducted at the University of Jyväskylä Sports and Health Science laboratory.Three hundred ninety-six healthy Finnish girls aged 11.2 ± 0.8 years participated in the study.Body composition was ass…
Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis
Toll-like receptor 5 ligand, flagellin, and vascular adhesion protein 1 (VAP-1) are involved in non-alcoholic fatty liver disease. This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected into C57BL/6J (WT) and C57BL/6-Aoc3-/- (VAP-1 KO) mice on a high-fat diet twice a week every 2 weeks for 10 weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin cha…
Genotype determining aerobic exercise capacity associates with behavioral plasticity in middle-aged rats
Good aerobic fitness associates positively with cognitive performance and brain health and conversely, low aerobic fitness predisposes to neurodegenerative diseases. To study how genotype together with exercise, started at older age, affects brain and behavior, we utilized rats that differ in inherited aerobic fitness. Rats bred for Low Capacity for Running (LCR) are shown to display less synaptic plasticity and more inflammation in the hippocampus and perform worse than rats bred for a High Capacity for Running (HCR) in tasks requiring flexible cognition. Here we used middle-aged (∼ 16 months) HCR and LCR rats to study how genotype and sex associate with anxiety and neural information filt…
Serum metabolic profiles in overweight and obese women with and without metabolic syndrome.
Objective: To identify serum biomarkers through metabolomics approach that distinguishes physically inactive overweight/obese women with metabolic syndrome from those who are metabolically healthy, independent of body weight and fat mass. Methods: We applied nuclear magnetic resonance spectroscopy-based profiling of fasting serum samples to examine the metabolic differences between 78 previously physically inactive, body weight and fat mass matched overweight/obese premenopausal women with and without MetS. MetS was defined as the presence of at least three of the following five criteria: waist circumference ≥ 88 cm, serum triacylglycerol ≥ 1.7 mmol/L, and high density lipoprotein cholester…
Irradiation of the head reduces adult hippocampal neurogenesis and impairs spatial memory, but leaves overall health intact in rats.
Treatment of brain cancer, glioma, can cause cognitive impairment as a side‐effect, possibly because it disrupts the integrity of the hippocampus, a structure vital for normal memory. Radiotherapy is commonly used to treat glioma, but the effects of irradiation on the brain are still poorly understood, and other biological effects have not been extensively studied. Here we exposed healthy adult male rats to small and moderate‐dose irradiation of the head. We found no effect of irradiation on systemic inflammation, weight gain or gut microbiota diversity, although it increased the abundance of Bacteroidaceae family, namely Bacteroides genus in the gut microbiota. Irradiation had no effect on…
Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease
Numerous studies have described specific metabolites as biomarkers ofsevere liver diseases, but very few have measured gut microbiota (GM)-produced metab-olites in fatty liver disease. We aimed atfinding GM signatures and metabolite markersin plasma and feces related to high liver fat content. Based on imaging, we dividedstudy participants into low (,5%, LF,n= 25) and high (.5%, HF,n= 39) liver fatgroups. Fecal (LFn= 14, HFn= 25) and plasma (LFn= 11, HFn= 7) metabolomes ofsubsets of participants were studied using liquid chromatography/high resolution massspectrometry. The GM were analyzed using 16S rRNA gene sequencing. Additionally,blood clinical variables and diet were studied. Dyslipide…
Cannabinoid receptor 1 and acute resistance exercise – In vivo and in vitro studies in human skeletal muscle
Abstract Aim This study aimed to determine whether Cannabinoid receptor 1 (CB1) is involved in mammalian target of rapamycin (mTOR) signaling and skeletal muscle protein synthesis. Methods This study used human vastus lateralis skeletal muscle biopsies obtained before and after a resistance exercise (RE) bout in young men (n = 18). The signaling mechanisms were studied in vitro in human myotubes. Protein expression was determined by Western blot and confocal microscopy, and gene expression by quantitative PCR. Protein synthesis was measured in vitro using puromycin-based SuNSET technique. Results In human skeletal muscle, an anabolic stimulus in the form of RE down-regulated CB1 expression.…
Serum cytokines in elite skiing athletes associate with triglyceride metabolism
Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus.
Abstract BACKGROUND Increasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats. METHODS We examined markers for inflammation and brain plasticity in the hippocampi of LCR…
Effect of aerobic exercise and low carbohydrate diet on pre-diabetic non-alcoholic fatty liver disease in postmenopausal women and middle aged men: study protocol for the AELC randomized controlled trial
Background. Pre-diabetes and non-alcoholic fatty liver disease (NAFLD) are associated with an unhealthy lifestyle and pose extremely high costs to the healthcare system. In this study, we aim to explore whether individualized aerobic exercise (AEx) and low carbohydrate diet (LCh) intervention affect hepatic fat content (HFC) in pre-diabetes via modification of gut microbiota composition and other post-interventional effects. Methods/design. A 6-month randomized intervention with 6-month follow-up is conducted from January 2013 to December 2015. The target sample size for intervention is 200 postmenopausal women and middle-aged men aged 50–65 year-old with pre-diabetes and NAFLD. The qualifi…
Shorter recovery time following high-intensity interval training induced higher body fat loss among overweight women
Background: High intensity interval training (HIIT) has been widely employed as an exercise protocol to reduce fat, and also in addition, interval recovery periods are the most important factors which can have great impact on weight loss. Therefore, the aim of this study was the evaluation of different recovery time between HIIT program on metabolic responses and weight loss in overweight women. Methods: Twenty-four overweight (BMI 29.5±3.5 kg/m2) volunteer women were randomly assigned into three groups (n=8/group) to study the effects of different recovery times: (group 1; HIIT with 60/60 activity-rest ratio (sec), group 2; HIIT with 60/30 activity-rest ratio (sec), and group 3 was set as …
Toll-like receptor 5 in obesity: The role of gut microbiota and adipose tissue inflammation
Objective This study aimed at establishing bacterial flagellin-recognizing toll-like receptor 5 (TLR5) as a novel link between gut microbiota composition, adipose tissue inflammation, and obesity. Methods An adipose tissue microarray database was used to compare women having the highest (n = 4, H-TLR) and lowest (n = 4, L-TLR) expression levels of TLR5-signaling pathway genes. Gut microbiota composition was profiled using flow cytometry and FISH. Standard laboratory techniques were used to determine anthropometric and clinical variables. In vivo results were verified using cultured human adipocytes. Results The H-TLR group had higher flagellated Clostridium cluster XIV abundance and Firmicu…
Gut-adipose tissue axis in hepatic fat accumulation in humans
Recent evidence suggests that in animals gut microbiota composition (GMC) affects the onset and progression of hepatic fat accumulation. The aim of this study was to investigate in humans whether subjects with high hepatic fat content (HHFC) differ in their GMC from those with low hepatic fat content (LHFC), and whether these differences are associated with body composition, biomarkers and abdominal adipose tissue inflammation.Hepatic fat content (HFC) was measured using proton magnetic resonance spectroscopy ((1)H MRS). Fecal GMC was profiled by 16S rRNA fluorescence in situ hybridization and flow cytometry. Adipose tissue gene expression was analyzed using Affymetrix microarrays and quant…