Paavo Rahkila

Effects of diet-induced obesity and voluntary wheel running on the microstructure of the murine distal femur

BackgroundObesity and osteoporosis, two possibly related conditions, are rapidly expanding health concerns in modern society. Both of them are associated with sedentary life style and nutrition. To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (μCT) together with peripheral quantitative computed tomography (pQCT) to examine the microstructure of the distal femoral metaphysis in mice.MethodsForty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C), control + running (CR), high-fat diet (HF), and high-fat diet + running (HFR). After a 21-week intervention, all the mice were sacrificed and the left femur dissected for pQCT and μCT measurements.ResultsThe mice fed the high-fat diet showed a significant weight gain (over 70% for HF and 60% for HFR), with increased epididymal fat pad mass and impaired insulin sensitivity. These obese mice had significantly higher trabecular connectivity density, volume, number, thickness, area and mass, and smaller trabecular separation. At the whole bone level, they had larger bone circumference and cross-sectional area and higher density-weighted maximal, minimal, and polar moments of inertia. Voluntary wheel running decreased all the cortical bone parameters, but increased the trabecular mineral density, and decreased the pattern factor and structure model index towards a more plate-like structure.ConclusionsThe results suggest that in mice the femur adapts to obesity by improving bone strength both at the whole bone and micro-structural level. Adaptation to running exercise manifests itself in increased trabecular density and improved 3D structure, but in a limited overall bone growth

Long-term Leisure-time Physical Activity and Serum Metabolome

Background— Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk. Methods and Results— Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their >30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 population-based cohorts (mean ages, 31–52 years) were also studied (1037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the significance of the multivariate effect combined across all metabolic measures; univariate effects were estimated by paired testing in twins and in matched pairs in the cohorts, and by meta-analysis over all substudies. Persistent physical activity was associated with the multivariate metabolic profile in the twins (P=0.003), and a similar pattern was observed in all 3 population cohorts with differing mean ages. Isoleucine, &agr;1-acid glycoprotein, and glucose were lower in the physically active than in the inactive individuals (P<0.001 in meta-analysis); serum fatty acid composition was shifted toward a less saturated profile; and lipoprotein subclasses were shifted toward lower very-low-density lipoprotein (P<0.001) and higher large and very large high-density lipoprotein (P<0.001) particle concentrations. The findings persisted after adjustment for body mass index. Conclusions— The numerous differences found between persistently physically active and inactive individuals in the circulating metabolome together indicate better metabolic health in the physically active than in inactive individuals.

Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes

Endocrine responses in seven power athletes were investigated during a 12 week strength training period, when the athletes were taking high doses of andro genic-anabolic steroids, and during the 13 weeks fol lowing drug withdrawal. During the use of steroids significant decreases (P < 0.05 to 0.001) in the serum concentrations of thyroid stimulating hormone, thyrox ine, triidothyronine, free thyroxine, and thyroid hor mone-binding globulin (TBG) were found, whereas the value of triidothyronine uptake increased (P < 0.001). In relation to the changes in the thyroid function param eters measured, we suggest that the primary target of androgen action was TBG biosynthesis. In five of the seven subjects, serum concentrations of growth hor mone increased at some point of the study 5 to 60- fold. Because of the use of exogenous testosterone, serum testosterone concentration tended to increase. This increase was associated with a corresponding increase (P < 0.001) in serum estradiol. Furthermore, there were major decreases in serum LH (P < 0.01) and FSH (P < 0.01) concentrations, and testicular tes tosterone production was therefore decreased. This was characterized by a very low serum testosterone concentration (5.1 ± 1.8 nmol/l) 4 weeks following drug withdrawal. Cessation of drug use resulted in return of all the variables measured to the initial values, except for serum testosterone, which was at a low level (14.6 ± 8.8 nmol/l) 9 weeks after drug withdrawal, indicating prolonged impairment of testicular endocrine function. No consistent changes were found in the eight control athletes.

Differences in Muscle and Adipose Tissue Gene Expression and Cardio-Metabolic Risk Factors in the Members of Physical Activity Discordant Twin Pairs

High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50–74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased ‘high-risk’ ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced cardio-metabolic risk.

Muscle metabolism, blood lactate and oxygen uptake in steady state exercise at aerobic and anaerobic thresholds

SummaryMuscle metabolites and blood lactate concentration were studied in five male subjects during five constant-load cycling exercises. The power outputs were below, equal to and above aerobic (AerT) and anaerobic (AnT) threshold as determined during an incremental leg cycling test. At AerT, muscle lactate had increased significantly (p<0.05) from the rest value of 2.31 to 5.56 mmol · kg−1 wet wt. This was accompanied by a significant reduction in CP by 28% (p<0.05), whereas only a minor change (9%) was observed for ATP. At AnT muscle lactate had further increased and CP decreased although not significantly as compared with values at AerT. At the highest power outputs (> AnT) muscle lactate had increased (p<0.01) and CP decreased (p<0.01) significantly from the values observed at AnT. Furthermore, a significant reduction (p<0.05) in ATP over resting values was recorded. Blood lactate decreased significantly (p<0.01) during the last half of the lowest 5 min exercise, remained unchanged at AerT and increased significantly (p<0.05–0.01) at power outputs ⩾AnT. It is concluded that anaerobic muscle metabolism is increased above resting values at AerT: at low power outputs (⩽AerT) this could be related to the transient oxygen deficit during the onset of exercise or the increase in power output. At high power outputs (> AnT) anaerobic energy production is accelerated and it is suggested that AnT represents the upper limit of power output where lactate production and removal may attain equilibrium during constant load exercise.

Bone mineral density of the calcaneus in 70- to 81-yr-old male athletes and a population sample

Bone mineral content (BMC/W) and density (BMD) were studied in 70- to 81-yr-old active male endurance-trained (long-distance runners, cross-country skiers, N = 67), strength-trained (throwers, weight-lifters, N = 14), and speed-trained (sprinters, jumpers, N = 16) athletes. A population sample of similar age (N = 42) served as a control group. The measurements were performed at the calcaneus by single-energy photon absorption. The endurance-trained athletes had higher bone width and depth, and the strength and speed-trained athletes higher bone depth than the control subjects. The three groups of athletes showed 19-28% higher BMC (g.cm-1) and BMC/W (g.cm-2) than the control group (P less than 0.01-0.001). When the results were corrected for bone depth by assessing BMD (g.cm-3), the mean differences between the athletes and controls were 11-16% (P less than 0.05-0.01, not significant for the strength group). The highest BMD values were associated with moderate training for running and cross-country skiing. BMD did not correlate with serum total testosterone, but there was a negative correlation between BMD and sex hormone binding globulin and a positive correlation between BMD and the free androgen index in the endurance group. The results indicate that athletes having a long-term training history and being still active at over 70 yr of age preserve superior trabecular bone mass compared with the average male population of the same age.

Anabolic-Androgenic Steroid Effects on Endocrinology and Lipid Metabolism in Athletes

As exhaustive reviews concerning hormonal alteration (Bunt 1986) and lipid metabolism (Goldberg & Elliot 1987; Hurley & Kokkinos 1987) during normal physical exercise and training have recently been published in the Journal, this article is designed to focus only on the biological actions of synthetic anabolic-androgenic steroids on endocrinology and lipid metabolism and the interactions between both of these during training in adult male athletes.

Metabolic changes induced by combined prolonged exercise and low-calorie intake in man

SummaryThirteen middle-aged women and 10 men walked 344 km during 7 days. The daily walking distances were 57, 53, 67, 53, 41, 36, and 37 km at an average speed of 3.5 km·h−1. During the hike the subjects drank water, mineral drinks, and juices ad libitum. Except for some natural products, no food intake was allowed. During the hike the body weight and serum protein concentration of the subjects decreased by about 7%, on average. Serum triglyceride and total cholesterol decreased drastically, about 30–40% during the hike, but HDL-cholesterol showed a tendency to increase, giving a 40% increment in HDL/total cholesterol ratio. Serum free fatty acids rose 1.5–2 times above the starting level. Serum glucose and evening insulin levels decreased significantly during the hike. Serum cortisol in evening samples after the daily walking and plasma norepinephrine concentrations were significantly increased, reflecting the immediate daily response to the combined fasting and walking. Serum testosterone levels decreased in men but not in women, indicating the involvement of the LH-testis pathway in the decrease obtained. Serum ASAT activity rose to about three times the starting level during the hike, whereas γ-GT activity gradually decreased. These marked metabolic changes caused by combined fasting and several days exercise were in many respects (as in cholesterol, HDL/total cholesterol ratio or testosterone levels) more pronounced than those earlier reported to be caused by exercise or fasting alone.

Vertical jumping height and horizontal overhead throwing velocity in young male athletes

The purpose of this study was to examine the effects of calendar and skeletal age, anthropometric dimensions, training history and their interactions on vertical jumping height and horizontal overhead throwing velocity in a cross-section of 318 young male athletes (age range 9-16 years) participating in cross-country skiing (n = 70), basketball (n = 40), apparatus gymnastics (n = 19), ice hockey (n = 50), track and field (n = 89) and wrestling (n = 50). Vertical jumping height was measured with four different loads held on the shoulders and then interpolated for loads representing 0 and 40% body mass. Horizontal overhead throwing velocity using both hands was determined for seven balls of different weights and then interpolated for weights representing 1 and 5% body mass. Both vertical jumping height and overhead throwing velocity were found to increase (P < 0.01) from the skeletally youngest to the oldest cohort when the effects of body height and mass were controlled. The inter-event comparisons did not reveal statistically significant differences in respect of vertical jumping height. Also in the overhead throwing tests, the inter-event differences were small, although the analysis of variance revealed statistically significant (P < 0.001) differences for the skeletal age cohorts of 13 and 14 years. While the quantity of training had no effect on vertical jumping height, it explained the results in the overhead throwing test. The effects of training on vertical jumping and horizontal overhead throwing among adolescent athletes were considered to be small, while maturational processes and anthropometric development followed by increase in calendar age were deemed to be of greater importance.

Cellular and tissue expression of DAPIT, a phylogenetically conserved peptide

DAPIT (Diabetes Associated Protein in Insulin-sensitive Tissues) is a small, phylogenetically conserved, 58 amino acid peptide that was previously shown to be down-regulated at mRNA level in insulin-sensitive tissues of type 1 diabetes rats. In this study we characterize a custom made antibody against DAPIT and confirm the mitochondrial presence of DAPIT on cellular level. We also show that DAPIT is localized in lysosomes of HUVEC and HEK 293T cells. In addition, we describe the histological expression of DAPIT in several tissues of rat and man and show that it is highly expressed especially in cells with high aerobic metabolism and epithelial cells related to active transport of nutrients and ions. We propose that DAPIT, in addition to indicated subunit of mitochondrial F-ATPase, is also a subunit of lysosomal V-ATPase suggesting that it is a common component in different proton pumps.