0000000000138091
AUTHOR
Eveliina Munukka
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…
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…
The Association between Cardiorespiratory Fitness and Gut Microbiota Composition in Premenopausal Women
Abstract The aim of this study was to investigate the association between cardiorespiratory fitness and gut microbiota composition in premenopausal women. The participants consisted of 71 premenopausal Finnish women (aged 19–49 years). Gut microbiota were analyzed using flow cytometry, 16S rRNA gene hybridization and DNA-staining. Maximum oxygen uptake (VO₂ₘₐₓ) was assessed by respiratory gas analyzer and body composition by Bioimpdance. We found that participants with low VO₂ₘₐₓ had lower Bacteroides, but higher Eubacterium rectale-Clostridium coccoides than the high VO₂ₘₐₓ group (p < 0.05 for all). VO₂ₘₐₓ was inversely associated with EreC (r = −0.309, p = 0.01) but not with other bact…
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…
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…
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…
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…
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…
Is bone loss the reversal of bone accrual? Evidence from a cross-sectional study in daughter-mother-grandmother trios.
Bone adapts to mechanical loads applied on it. During aging, loads decrease to a greater extent at those skeletal sites where loads increase most in earlier life. Thus, the loss of bone may occur preferentially at sites where most bone has been deposited previously; ie, bone loss could be the directional reversal of accrual. To test this hypothesis, we compared the bone mass distribution at weight-bearing (tibia) and non-weight-bearing (radius) bones among 18-year-old girls, their premenopausal mothers, and their postmenopausal maternal grandmothers. Bone and muscle properties were measured by pQCT, and polar distribution of bone mass was obtained in 55 girl-mother–maternal grandmother trio…
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…
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…
Prolonged breast-feeding protects mothers from later-life obesity and related cardio-metabolic disorders
AbstractObjectiveTo investigate the long-term effects of duration of postpartum lactation on maternal body composition and risk for cardio-metabolic disorders in later life.DesignRetrospective study. Body composition was measured using dual-energy X-ray absorptiometry and serum glucose, insulin and lipids were analysed using enzymatic photometric methods 16–20 years after the last pregnancy. Medical history and lifestyle factors were collected via a self-administered questionnaire. Detailed information regarding weight change patterns during each pregnancy was obtained from personal maternity tracking records.SettingCity of Jyväskylä and surroundings in Central Finland.SubjectsTwo hundred a…
Concerted actions of insulin-like growth factor 1, testosterone, and estradiol on peripubertal bone growth: a 7-year longitudinal study.
A better understanding of how bone growth is regulated during peripuberty is important for optimizing the attainment of peak bone mass and for the prevention of osteoporosis in later life. In this report we used hierarchical models to evaluate the associations of insulin-like growth factor 1 (IGF-1), estradiol (E(2) ), and testosterone (T) with peripubertal bone growth in a 7-year longitudinal study. Two-hundred and fifty-eight healthy girls were assessed at baseline (mean age 11.2 years) and at 1, 2, 3.5, and 7 years. Serum concentrations of IGF-1, E(2) , and T were determined. Musculoskeletal properties in the left lower leg were measured using peripheral quantitative computed tomography …
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…
Effect of long-term leisure time physical activity on lean mass and fat mass in girls during adolescence.
The purpose of this 7-yr prospective longitudinal study was to examine if the level and consistency of leisure-time physical activity (LTPA) during adolescence affected the quantity and distribution of lean mass (LM) and fat mass (FM) at early adulthood. The study subjects were 202 Finnish girls who were 10–13 yr old at baseline. LM and FM of the total body (TB), arms, legs, and trunk were assessed by dual-energy X-ray absorptiometry. Muscle cross-sectional area (mCSA) of the left leg was assessed by peripheral quantitative computed tomography. Scores of LTPA were obtained by questionnaire. Girls were divided into four groups comprising those with consistently low (GLL) or consistently hig…
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…
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…
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.…
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…
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…