Jesper Løvind Andersen

Evidence of an Increased Number of Type IIb Muscle Fibers in Insulin-Resistant First-Degree Relatives of Patients with NIDDM

Insulin resistance is a common feature in first-degree relatives of NIDDM patients. To explore the mechanism(s) behind this condition in more detail, a percutaneous muscle biopsy (vastus lateralis) was performed in 25 first-degree relatives of NIDDM patients and 21 control subjects to examine muscle fiber composition and capillary density. Insulin-stimulated glucose disposal (Rd) was determined employing a hyperinsulinemic-(insulin infusion rate 0.6 mU · kg−1 · min−1) euglycemic clamp. Rd (5.76 ± 0.35 vs. 8.06 ± 0.36 mg · kg lean body weight [LBW]−1 · min−1 P < 0.001) and estimated Vo2max (49.3 ± 2.8 vs. 57.2 ± 3.5 mg · kg LBW−1 · min−1, 0.05 < P < 0.10) were decreased in the relatives. The number of type lib fibers (29.5 ± 2.5 vs. 21.0 ± 2.8%, P < 0.05) was increased in the relatives, whereas no significant differences were found in other fiber types or capillary density between the groups. Correlations were observed between number of type I fibers (positive), number of type lib fibers (negative), and capillary density (positive) versus Rd as well as estimated Vo3max (P < 0.05). In a multiple linear regression analysis with Rd as a dependent variable, estimated Vo2max, family history of NIDDM, and number of type lib fibers (P < 0.001, r2 = 0.64) significantly determined the level of Rd, whereas capillary density did not. In conclusion, insulin-resistant first-degree relatives of NIDDM patients are characterized by an increased number of type lib muscle fibers. Whether this finding reflects a reduced physical activity level and fitness in the relatives or is of primary genetic origin remains to be determined.

Early and late rate of force development: differential adaptive responses to resistance training?

The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high‐intensity resistance training on contractile rate of force development (RFD) in the early (<100u2003ms) and later phases (>200u2003ms) of rising muscle force. Fifteen healthy young males participated in a 14‐week resistance training intervention for the lower body and 10 matched subjects participated as controls. Maximal muscle strength (MVC) and RFD were measured during maximal voluntary isometric contraction of the quadriceps femoris muscle. Muscle biopsies were obtained from the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross‐sectional area and MVC increased whereas, qualitatively, the relative proportion of type IIX muscle fibers decreased. Multiple regression analysis showed that while increased MVC positively influenced both early and late RFD, decreased‐type IIX negatively influenced early RFD only. In conclusion, early and late RFD responded differently to high‐intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force.

Elevated Levels of IL-18 in Plasma and Skeletal Muscle in Chronic Obstructive Pulmonary Disease

The aim of this study was to test the hypothesis that systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) is accompanied by enhanced interleukin 18 (IL-18) expression in skeletal muscle, which may precede muscle weight loss. Twenty patients with moderate to severe COPD [12 women, 66xa0±xa09.4 years of age and forced expiratory volume in 1 second (FEV1) of 32%xa0±xa012 % of predicted value] and 20 healthy age-, gender-, and body mass index (BMI)-matched controls (10 nonsymptomatic smokers and 10 nonsmokers) were included in the study. Plasma levels of IL-18 were elevated in COPD patients (nxa0=xa020) versus healthy controls (nxa0=xa020) (221.2 pg/ml [196.0–294.2 pg/pl] vs. 164.8 pg/ml [144.4–193.3 pg/pl], pxa0=xa00.04) and IL-18 was expressed in skeletal muscle, with IL-18 mRNA levels being elevated in biopsies from COPD patients (nxa0=xa019) versus healthy controls (nxa0=xa018) (4.3 [2.6–5.9] vs. 2.4 [1.6–3.1], pxa0=xa00.003). Immunohistochemical evaluation revealed a strong expression of IL-18 in Type II muscle fibers from COPD patients. Plasma levels and skeletal muscle mRNA levels of tumor necrosis factor α (TNF-α) and IL-6 did not differ between the groups. Elevated skeletal muscle expression of IL-18 was found in COPD patients with normal body weight, indicating that IL-18 potentially may be involved in the pathogenesis of COPD-associated muscle wasting.

Are substrate use during exercise and mitochondrial respiratory capacity decreased in arm and leg muscle in type 2 diabetes

Aim/hypothesisThe aim of the study was to investigate mitochondrial function, fibre type distribution and substrate oxidation in arm and leg muscle during exercise in patients with type 2 diabetes and in obese and lean controls.MethodsIndirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsies from arm and leg were obtained. Fibre type, as well as O2 flux capacity of saponin-permeabilised muscle fibres were measured, the latter by high resolution respirometry, in patients with type 2 diabetes, age- and BMI-matched obese controls, and age-matched lean controls.ResultsFat oxidation was similar in the groups during either arm or leg exercise. During leg exercise at higher intensities, but not during arm exercise, carbohydrate oxidation was lower in patients with type 2 diabetes compared with the other groups. In patients with type 2 diabetes, ADP-stimulated state 3 respiration per mg muscle with parallel electron input from complex I+II was lower in m. vastus lateralis compared with obese and lean controls, whereas no differences between groups were present in m. deltoideus. A higher percentage of type IIX fibres was seen in m. vastus lateralis in patients with type 2 diabetes compared with obese and lean controls, whereas no difference was found in the deltoid muscle.Conclusions/interpretationThis study demonstrates similar O2 flux capacity, fibre type distribution and carbohydrate oxidation in arm muscle in the groups despite the presence of attenuated values in leg muscle in patients with type 2 diabetes compared with obese and lean controls.

Increased proportion of megafibers in chronically painful muscles.

Abstract Trapezius myalgia – chronic pain from the upper trapezius muscle – is frequent in female employees in monotonous stressful jobs, potentially due to chronic overload of type I muscle fibers. In this study, we investigated the intra‐individual distribution of trapezius muscle fiber size, and hypothesized that females with myalgia compared with matched healthy controls have a higher percentage of grossly hypertrophied type I fibers with poor capillarization. Forty‐two female office workers with trapezius myalgia (MYA) and 20 healthy matched controls (CON) participated in the study. Standard histochemical methods were used to determine fiber size, fiber type, and capillarization. Type I megafiber were defined as at least twice the size of the median type I fiber size of each individual. The main finding was that MYA had a significantly higher proportion of type I megafibers than CON, in spite of no significant difference in overall type I fiber size. In MYA and CON type I megafibers were located in 46% and 11% of the females, respectively. Capillarization of the overall type I fiber pool was not different between CON and MYA, but was significantly lower in type I megafibers of both groups. The percentage of megafibers was positively related to age and weekly working hours, indicating an effect of long‐term exposure. In conclusion, this study shows that trapezius myalgia is associated with a significantly higher percentage of grossly hypertrophied type I muscle fibers with poor capillarization – type I megafibers.

Timing of post‐exercise protein intake is important for muscle hypertrophy with resistance training in elderly humans

(1) Age‐associated loss of skeletal muscle mass and strength can partly be counteracted by resistance training, causing a net synthesis of muscular proteins. Protein synthesis is influenced synergistically by post‐exercise amino acid supplementation, but the importance of the timing of protein intake remains unresolved. (2) The study investigated the importance of immediate (P0) or delayed (P2) intake of an oral protein supplement upon muscle hypertrophy and strength over a period of resistance training in elderly males. (3) Thirteen men (age 74u2003±u20031u2003years; body mass index (BMI), 25u2003±u20031u2003kg m−u20032 (means ± SEM)) completed a 12‐week resistance training program (three times per week) receiving oral protein in liquid form (10 g protein, 7 g carbohydrate, 3 g fat) immediately after (P0) or 2 h after (P2) each training session. Muscle hypertrophy was evaluated by magnetic resonance imaging (MRI) and from muscle biopsies and muscle strength was determined using dynamic and isokinetic strength measurements. Body composition was determined from dual‐energy X‐ray absorptiometry (DEXA) and food records were obtained over 4u2003days. The plasma insulin response to protein supplementation was also determined. (4) In response to training, the cross‐sectional area of m. quadriceps femoris (54.6u2003±u20030.5–58.3u2003±u20030.5u2003cm2) and mean fiber area (4047u2003±u2003320–5019u2003±u2003615 μ m2) increased in the P0 group, whereas no significant increase was observed in P2. For P0 both dynamic and isokinetic strength increased, by 46 and 15%, respectively (Pu2003<u20030.05), whereas P2 only improved in dynamic strength, by 36% (Pu2003<u20030.05). No differences in glucose or insulin response were observed between protein intake at 0 and 2 h post‐exercise. (5) We conclude that early intake of an oral protein supplement after resistance training is important for the development of hypertrophy in skeletal muscle of elderly men in response to resistance training.

Changed mitochondrial function by pre- and/or postpartum diet alterations in sheep

In a sheep model, we investigated diet effects on skeletal muscle mitochondria to look for fetal programming. During pregnancy, ewes were fed normally (N) or were 50% food restricted (L) during the last trimester, and lambs born to these ewes received a normal (N) or a high-fat diet (H) for the first 6 mo of life. We examined mitochondrial function in permeabilized muscle fibers from the lambs at 6 mo of age (adolescence) and after 24 mo of age (adulthood). The postpartum H diet for the lambs induced an approximately 30% increase (P < 0.05) of mitochondrial VO(2max) and an approximately 50% increase (P < 0.05) of the respiratory coupling ratio (RCR) combined with lower levels of UCP3 and PGC-1alpha mRNA levels (P < 0.05). These effects proved to be reversible by a normal diet from 6 to 24 mo of age. However, at 24 mo, a long-term effect of the maternal gestational diet restriction (fetal programming) became evident as a lower VO(2max) (approximately 40%, P < 0.05), a lower state 4 respiration (approximately 40%, P < 0.05), and lower RCR ( approximately 15%, P < 0.05). Both PGC-1alpha and UCP3 mRNA levels were increased (P < 0.05). Two analyzed muscles were affected differently, and muscle rich in type I fibers was more susceptible to fetal programming. We conclude that fetal programming, seen as a reduced VO(2max) in adulthood, results from gestational undernutrition. Postnatal high-fat diet results in a pronounced RCR and VO(2max) increase in adolescence. However, these effects are reversible by diet correction and are not maintained in adulthood.

Muscle ceramide content in man is higher in type I than type II fibers and not influenced by glycogen content

Human muscle is studied during glycogen depletion and repletion to understand the influence of exercise and muscle glycogen on total ceramide content. In addition, fiber-type-specific ceramide storage is investigated. Ten healthy males (26.4xa0±xa00.9xa0years, BMI 24.4xa0±xa00.7xa0kgxa0m−2 and VO2max 57xa0±xa02xa0mLxa0O2xa0min−1xa0kg−1) participated in the study. On the first day, one leg was glycogen-depleted (DL) by exhaustive intermittent exercise followed by low carbohydrate diet. Next day, in the overnight fasted condition, muscle biopsies were excised from vastus lateralis before and after exhaustive exercise from both DL and control leg (CL). Muscle glycogen was analyzed biochemically and total muscle ceramide content by 2D quantitative lipidomic approach. Furthermore, fiber-type ceramide content was determined by fluorescence immunohistochemistry. Basal muscle glycogen was decreased (Pxa0<xa00.05) with 50xa0±xa06% in DL versus CL. After exhaustive exercise, muscle glycogen was similar in CL and DL 139xa0±xa038 and 110xa0±xa031xa0mmolxa0kg−1, respectively. Total muscle ceramide 58xa0±xa01xa0pmolxa0mg−1 was not influenced by glycogen or exercise. Ceramide content was consistently higher (Pxa0<xa00.001) in type I than in type II muscle fibers. In conclusion, human skeletal muscle, ceramide content is higher in type I than in type II. Despite rather large changes in muscle glycogen induced by prior depletion, exercise to exhaustion and repletion, total muscle ceramide concentration remained unchanged.

Four weeks one-leg training and high fat diet does not alter PPARα protein or mRNA expression in human skeletal muscle

Fatty acid metabolism is influenced by training and diet with exercise training mediating this through activation of nuclear hormone receptor peroxisome proliferator-activated receptor α (PPARα) in skeletal muscle. This study investigated the effect of training and high fat or normal diet on PPARα expression in human skeletal muscle. Thirteen men trained one leg (T) four weeks (31.5xa0h in total), while the other leg (UT) served as control. During the 4xa0weeks six subjects consumed high fat (FAT) diet and seven subjects maintained a normal (CHO) diet. Biopsies were obtained from vastus lateralis muscle in both legs before and after training. After the biopsy, one-leg extension exercise was performed in random order with both legs 30xa0min at 95% of workload max. A training effect was evident as citrate synthase activity increased (Pxa0<xa00.05) by 15% in the trained, but not the control leg in both groups. During exercise respiratory exchange ratio was lower in FAT (0.86xa0±xa00.01, 0.83xa0±xa00.01, meanxa0±xa0SEM) than CHO (0.96xa0±xa00.02, 0.94xa0±xa00.03) and in UT than T legs, respectively. The PPARα protein (144xa0±xa044, 104xa0±xa028, 79xa0±xa015, 79xa0±xa014, % of pre level) and PPARα mRNA (69xa0±xa0[2, 2], 78xa0±xa0[7, 6], 92xa0±xa0[22, 18], 106xa0±xa0[21, 18], % of pre level, geometric meanxa0±xa0SEM) expression remained unchanged by diet and training in FAT (UT, T) and CHO (UT, T), respectively. After the training and diet CS, HAD, PPARα, UCP2, UCP3 and mFABP mRNA content remained unchanged, whereas GLUT4 mRNA was lower in both groups and LDHA mRNA was lower (Pxa0<xa00.05) only in FAT. In conclusion: 4xa0weeks one leg knee extensor training did not affect PPARα protein or mRNA expression. Furthermore, higher fat oxidation during exercise after fat rich diet was not accompanied by an increased PPARα protein or mRNA expression after 4xa0weeks.

Improved skeletal muscle mass and strength after heavy strength training in very old individuals.

ABSTRACT Age‐related loss of muscle mass and function represents personal and socioeconomic challenges. The purpose of this study was to determine the adaptation of skeletal musculature in very old individuals (83 + years) performing 12 weeks of heavy resistance training (3 ×/week) (HRT) compared to a non‐training control group (CON). Both groups received similar protein supplementations. We studied 26 participants (86.9 ± 3.2 (SD) (83–94, range) years old) per‐protocol. Quadriceps cross‐sectional area (CSA) differed between groups at post‐test (P < 0.05) and increased 1.5 ± 0.7 cm2 (3.4%) (P < 0.05) in HRT only. The increase in CSA is correlated inversely with the baseline level of CSA (R2 = 0.43, P < 0.02). Thigh muscle isometric strength, isokinetic peak torque and power increased significantly only in HRT by 10–15%, whereas knee extension one‐repetition maximum (1 RM) improved by 91%. Physical functional tests, muscle fiber type distribution and size did not differ significantly between groups. We conclude that in protein supplemented very old individuals, heavy resistance training can increase muscle mass and strength, and that the relative improvement in mass is more pronounced when initial muscle mass is low.