Satu Pekkala

Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health

•  Contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis and metabolic health, and the associated regulatory role of exercise and PGC‐1α. •  We analysed the effects of different short‐ and long‐term exercise regimens on muscle FNDC5 and PGC‐1α, and serum irisin, and studied the associations of irisin and FNDC5 with health parameters. •  FNDC5 and serum irisin did not change after acute aerobic, long‐term endurance training or endurance training combined with resistance exercise (RE) training, or associate with metabolic disturbances. A single RE bout increased FNDC5 mRNA in young, but not older men (27 vs. 62 years). Changes in PGC‐1α or serum irisin were not consistently accompanied by changes in FNDC5. •  Our data suggest that the effects of exercise on FNDC5 and irisin are not consistent, and that their role in health is questionable. Moreover, the regulatory mechanisms should be studied further.

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‐Clostridium coccoides group, indicating efficient energy harvest from nutrients in gut, was higher in MDG compared to NMDG and NWG, while no difference was found between NMDG and NWG. The proportion of Eubacterium rectale‐Clostridium coccoides group correlated positively with weight, BMI, total fat, fat mass percentage (FM%), visceral fat area, and serum triglycerides, and negatively with high‐density lipoprotein (HDL). Our results indicate that certain members of Eubacterium rectale‐Clostridium coccoides group are associated with obesity‐related MDs not obesity per se.

Serum Osteocalcin Is Not Associated with Glucose but Is Inversely Associated with Leptin across Generations of Nondiabetic Women

CONTEXT 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. OBJECTIVE The objective of the study was to examine the age-specific association between different forms of osteocalcin and glucose and adipokines. DESIGN This was a family-based study across three generations. SETTING The study was conducted at a university laboratory. PARTICIPANTS Sixty-four daughter-premenopausal mother-maternal grandmother trios participated in the study. METHODS Fasting plasma glucose and insulin concentrations, serum total (tOC), carboxylated (cOC), and uncarboxylated (ucOC = tOC - cOC) osteocalcin, leptin, and adiponectin levels, and fat masses were assessed. Generalized estimating equations (GEE) model was used to assess the associations of bone biomarkers with glucose metabolism variables and adipokines. RESULTS No significant difference in insulin was found between generations, whereas glucose and leptin increased with age. Levels of tOC, cOC, and ucOC were highest in girls and lowest in mothers (P < 0.01). Grandmothers had higher leptin and adiponectin than mothers and girls. Despite the differences in insulin and glucose between the low and high homeostasis model assessment insulin resistance index (HOMA-IR) groups within generations, no significant differences in tOC, cOC, and ucOC were found. Compared with their low HOMA-IR counterparts, the high HOMA-IR group had significantly higher leptin and lower adiponectin in mothers and grandmothers. The tOC, cOC, and ucOC levels did not correlate with HOMA-IR, leptin, or adiponectin when the three generations were evaluated together, but when separated by generation, leptin was inversely correlated with tOC (P = 0.003) and cOC (P = 0.047) in mothers and with ucOC in grandmothers (P = 0.042). CONCLUSIONS Osteocalcin, glucose, and adipokines change with age but in a noncommensurate manner. We infer that the association between osteocalcin and glucose metabolism is minor and age specific in nondiabetic women. Leptin, however, strongly correlated with insulin resistance independently of fat masses, suggesting that obesity, as a metabolic disorder risk factor, affects glucose metabolism, partly through the role of leptin.

Toll‐like receptor 5 in obesity: The role of gut microbiota and adipose tissue inflammation

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.

Toll-like Receptor 5 in Obesity: The Role of Gut Microbiota and Adipose Tissue Inflammation

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.

Gut-adipose tissue axis in hepatic fat accumulation in humans

BACKGROUND & AIMS 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. METHODS 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 quantitative PCR. RESULTS The HHFC group had unfavorable GMC described by lower amount of Faecalibacterium prausnitzii (FPrau) (p<0.05) and relatively higher Enterobacteria than the LHFC group. Metabolically dysbiotic GMC associated with HOMA-IR and triglycerides (p<0.05 for both). Several inflammation-related adipose tissue genes were differentially expressed and correlated with HFC (p<0.05). In addition, the expression of certain genes correlated with GMC dysbiosis, i.e., low FPrau-to-Bacteroides ratio. CONCLUSIONS HHFC subjects differ unfavorably in their GMC from LHFC subjects. Adipose tissue inflammation may be an important link between GMC, metabolic disturbances, and hepatic fat accumulation.

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 analyzed with 2 distinct protocols: 1 targeting the V3-V4 and the other targeting the V4-V5 area of the bacterial 16S rRNA gene. The overall effect of DNA extraction on the gut microbiota 16S rDNA profile was relatively small, whereas the 16S rRNA gene target region had an immense impact on the results. Furthermore, semiautomated DNA extraction methods clearly appeared suitable for NGS procedures, proposing that application of these methods could importantly reduce hands-on time and human errors without compromising the validity of results.

Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women.

Insulin 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 amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue.

Does Systemic Low-Grade Inflammation Associate With Fat Accumulation and Distribution? A 7-Year Follow-Up Study With Peripubertal Girls

CONTEXT 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. OBJECTIVE 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. DESIGN This was a 7.5-year longitudinal study. SETTING The study was conducted at the University of Jyväskylä Sports and Health Science laboratory. PARTICIPANTS Three hundred ninety-six healthy Finnish girls aged 11.2 ± 0.8 years participated in the study. METHODS Body composition was assessed by a dual-energy X-ray absorptiometry and serum concentrations of hsCRP, adipokines, and sex hormones by ELISA. RESULTS Both FM and hsCRP increased with age and had similar trajectories but different inter- and intravariance patterns. A joint analysis of fat distribution and hsCRP indicated that the linkage probabilities across different trajectory subgroups between regional FM and the corresponding hsCRP levels varied from 16% to 53%. In a longitudinal regression model, the common predictor for both FM and hsCRP was T (β = .065, P < 0.01, and β = -.213, P < 0.05, respectively) before menarche. Other factors predicting FM before menarche were SHBG (β = -.196, P < 0.01) and leptin (β = .381, P < .01); and after menarche hsCRP (β = .048, P < 0.01), T (β = .089, P < .01), leptin (β = .340, P < .01), and adiponectin (β = -.086, P < .05). Of the factors assessed, only FM was associated with hsCRP both before and after menarche (β =1.058, P < .01 and β =1.121, P < .01, respectively). CONCLUSIONS The differences in regional body fat depots and hsCRP levels in adulthood are largely established early in childhood. However, the intra- and interindividual variances differed between FM and hsCRP. FM explained the variance of hsCRP during pubertal growth, but the reverse was not true, which suggests that FM contributes to low-grade inflammation and not vice versa.

Effects of exercise and diet interventions on obesity-related sleep disorders in men: study protocol for a randomized controlled trial

BackgroundSleep 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 regulation.Methods/designParticipants consist of 330 (target sample) Finnish men aged 30 to 65 years. Among them, we attempt to randomize 180 (target sample) with sleep disorders into exercise and diet intervention. After screening and physician examination, 101 men with sleep disorders are included and are randomly assigned into three groups: exercise (n = 33), diet (n = 35), and control (n = 33). In addition, we attempt to recruit a target number of 150 healthy men without sleep disorders as the reference group. The exercise group undergoes a six-month individualized progressive aerobic exercise program based on initial fitness level. The diet group follows a six month specific individualized diet program. The control group and reference group are asked to maintain their normal activity and diet during intervention. Measurements are taken before and after the intervention. Primary outcomes include objective sleep measurements by polysomnography and a home-based non-contact sleep monitoring system, and subjective sleep evaluation by questionnaires. Secondary outcome measures include anthropometry, body composition, fitness, sleep disorder-related lifestyle risk factors, composition of gut microbiota and adipose tissue metabolism, as well as specific hormone and neurotranmitter levels and inflammatory biomarkers from venous blood samples.DiscussionIt is expected that the improvement of sleep quality after exercise and diet intervention will be evident both in subjective and objective measures of quality of sleep. Additionally, the change of sleep quality induced by exercise and diet intervention is expected to be related to the changes in specific hormones and inflammatory biomarkers, and in the composition of gut microbiota.Trial registrationCurrent Controlled Trials ISRCTN77172005