Petri Wiklund

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.

Prolonged breast-feeding protects mothers from later-life obesity and related cardio-metabolic disorders

OBJECTIVE To investigate the long-term effects of duration of postpartum lactation on maternal body composition and risk for cardio-metabolic disorders in later life. DESIGN Retrospective 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. SETTING City of Jyväskylä and surroundings in Central Finland. SUBJECTS Two hundred and twelve women (mean age 48, range 36-60 years). RESULTS At 16-20 years after their last pregnancy, women who had breast-fed for less than 6 months had higher total body fat mass and fat mass percentage, particularly in the android region (46·5 (sd 8·2) %) than mothers who had breast-fed for longer than 6 months (39·0 (sd 10·2) %) or for longer than 10 months (38·4 (sd 10·9) %, P < 0·01). These differences were independent of pre-pregnancy weight and BMI, menopausal status, smoking status, level of education, participation in past and present leisure-time physical activity, and current dietary energy intake. Higher body fat mass was also associated with higher fasting serum glucose concentration and insulin resistance, TAG, LDL cholesterol and total cholesterol concentrations, as well as higher systolic and diastolic blood pressure (P < 0·05 for all). CONCLUSIONS Short duration of breast-feeding may induce weight retention and fat mass accumulation, resulting in increased risk of cardio-metabolic disorders in later life.

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.

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 (E2), 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, E2, and T were determined. Musculoskeletal properties in the left lower leg were measured using peripheral quantitative computed tomography (pQCT). Serum levels of IGF‐1, E2, and T increased dramatically before menarche, whereas they decreased, plateaued, or increased at a lower rate, respectively, after menarche. IGF‐1 level was positively associated with periosteal circumference (PC) and total bone mineral content (tBMC) throughout peripuberty but not after adjustment for muscle cross‐sectional area (mCSA). On the other hand, IGF‐1 was associated with tibial length (TL) independently of mCSA before menarche. T was positively associated with TL, PC, tBMC, and cortical volumetric bone mineral density, independent of mCSA, before menarche but not after. E2 was associated with TL positively before menarche but negatively after menarche. These findings suggest that during puberty, circulating IGF‐1 promotes bone periosteal apposition and mass accrual indirectly, probably through stimulating muscle growth, whereas the effects of sex steroids on bone growth differ before and after menarche, presenting a biphasic pattern. Hence the concerted actions of these hormones are essential for optimal bone development in peripuberty.

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.

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

Background Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD. Methods Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS). Serum samples were analyzed using a nuclear magnetic resonance (NMR) metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot. Results Increased branched-chain amino acid (BCAA), aromatic amino acid (AAA) and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all). Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all), whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all). Conclusions Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

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.

Associations of disordered sleep with body fat distribution, physical activity and diet among overweight middle-aged men

This cross‐sectional study aimed to investigate whether body fat distribution, physical activity levels and dietary intakes are associated with insomnia and/or obstructive sleep apnea among overweight middle‐aged men. Participants were 211 Finnish men aged 30–65 years. Among the 163 overweight or obese participants, 40 had insomnia only, 23 had obstructive sleep apnea only, 24 had comorbid insomnia and obstructive sleep apnea and 76 were without sleep disorder. The remaining 48 participants had normal weight without sleep disorder. Fat mass, levels of physical activity and diet were assessed by dual‐energy X‐ray densitometry, physical activity questionnaire and 3‐day food diary, respectively. Among the overweight participants, we found that: (i) groups with sleep disorders had higher fat mass in trunk and android regions than the group without sleep disorder (P = 0.048–0.004); (ii) the insomnia‐only group showed a lower level of leisure‐time physical activity (436.9 versus 986.5 MET min week−1, P = 0.009) and higher intake of saturated fatty acids (14.8 versus 12.7 E%, P = 0.011) than the group without sleep disorder; and (iii) the comorbid group had a lower level of leisure‐time physical activity (344.4 versus 986.5 MET min week−1, P = 0.007) and lower folate intake (118.9 versus 152.1 μg, P = 0.002) than the group without sleep disorder, which were independent of body mass index. The results suggest that central obesity is associated with insomnia and/or obstructive sleep apnea. In addition, low levels of leisure‐time physical activity and poor dietary intakes are related to insomnia or comorbid insomnia and obstructive sleep apnea among overweight men.