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M K Hesselink

Publications and source records attributed to M K Hesselink.

18 recordsLinked to original sources
PubMed2005

Towards comprehension of the physiological role of UCP3.

Thyroid hormones have long been known to stimulate energy expenditure partly via loss of metabolic efficiency. The mechanism underlying the loss in metabolic efficiency observed, however, is not yet understood. An important candidate gene responsible for thyroid hormone induced thermogenesis was identified in 1997 with the discovery of skeletal muscle-uncoupling protein 3 (UCP3), a protein with approximately 60 % homology to the brown adipose tissue uncoupling protein 1 (UCP1). This short review summarizes our presentation held at the 'Thyroid and Sports' meeting; it does not aim to provide a concise overview of the available literature at this topic. Although induction of the UCP3 gene and increased protein expression during hyperthyroidism has been shown, there are no convincing data that increased UCP3 levels account for the increase in thermogenesis in the hyperthyroid state in humans. In contrast to cell and animal studies using ectopic overexpression of UCP3 as a model, induction of UCP3 in humans does not result in any apparent mitochondrial uncoupling. Hence, the primary physiological role of UCP3 may not be mitochondrial uncoupling, but uncoupling may occur as a side effect of a more pivotal role played by UCP3. Recently, UCP3 has been hypothesized to export fatty acid anions and/or lipid peroxides away from the mitochondrial matrix to prevent mitochondria from the harmful effects of peroxidized lipids. The present review aims to provide an overview of studies testing the feasibility of this unconventional function of UCP3.

Adipose Tissue↗
PubMed2001

Optimisation of oil red O staining permits combination with immunofluorescence and automated quantification of lipids.

The objective of the present study was to develop a stain permitting automated quantification of myocellular lipid depositions in skeletal muscle sections together with immunolocalisation of other myocellular constituents by fluorescence microscopy. Lipid droplets were detected in skeletal muscle by oil red O (ORO). Conventional ORO was modified to diminish background staining, prevent crystallisation of ORO and to optimise lipid retention in cryosections. These modifications resulted in a punctate staining of lipid droplets, rather than the somewhat diffuse staining by conventional ORO. Small cavities in muscle sections (like the lumen of small blood vessels) lack ORO when using the protocol presented here. In addition a staining protocol is presented combining ORO with immunofluorescence. This combination permits multiple staining studies in the same section. Thus, lipid droplets can be studied together with immunolabelling of proteins involved in lipid handling and metabolism. This will extend our knowledge on the subcellular localisation of lipid handling proteins (i.e. enzymes and fatty acid transporting proteins) in relation to the localisation of lipid depositions. In conclusion, the protocol presented here permits examination of ORO-stained lipid droplets in skeletal muscle sections together with multiple staining of other immunodetectable proteins present in skeletal muscle by quantitative fluorescence microscopy.

Animals↗
PubMed2001

In situ assessment of shortening and lengthening contractile properties of hind limb ankle flexors in intact mice.

The availability of animal models with disrupted genes has increased the need for small-scale measurement devices. Recently, we developed an experimental device to assess in situ mechanical properties of isometric contractions of intact muscle complexes of the mouse. Although this apparatus provides valuable information on muscle mechanical performance, it is not appropriate for determining contractile properties during shortening and lengthening contractions. In the present study we therefore developed and evaluated an experimental apparatus for assessment of shortening and lengthening contractile properties of intact plantar and dorsal flexors of the mouse. The current through a custom-built, low-inertia servomotor was measured to assess contractile muscular torque ranging from -50 to mN.m. Evaluation of the fixation procedure of the animal to the apparatus via 3-D monitoring of the muscle-tendon complex length showed that the additional shortening in length due to a contraction with maximal torque output has only minor effects on the measured torque. Furthermore, misalignment of the axis of rotation of the apparatus relative to the axis of rotation in the ankle joint, i.e. eccentricity, during a routine experiment was estimated to be less than 1.0 mm and hence did not influence the measured torque output under our experimental conditions. Peak power per unit muscle mass (mean +/- SD) of intact dorsal and plantar flexors was 0.27 +/- 0.02 and 0.19 +/- 0.03 W.g-1, respectively. The angular velocity at maximal peak power generated by the dorsal flexor complex and the plantar flexor complex was 1100 +/- 190 and 700 +/- 90 degrees.s-1, respectively.

Animals↗
PubMed2001

Passive transverse mechanical properties of skeletal muscle under in vivo compression.

The objective of the present study is to determine the passive transverse mechanical properties of skeletal muscle. Compression experiments were performed on four rat tibialis anterior muscles. To assess the stress- and strain-distributions in the muscle during the experiment, a plane stress model of the cross section was developed for each muscle. The incompressible viscoelastic Ogden model was used to describe the passive muscle behaviour. The four material parameters were determined by fitting calculated indentation forces on measured indentation forces. The elastic parameters, mu and alpha, were 15.6+/-5.4 kPa and 21.4+/-5.7, respectively. The viscoelastic parameters, delta and tau, were 0.549+/-0.056 and 6.01+/-0.42 s. When applying the estimated material parameters in a three-dimensional finite element model, the measured behaviour can be accurately simulated.

Animals↗
PubMed2001

An alternative function for human uncoupling protein 3: protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix.

The physiological function of the human uncoupling protein 3 UCP3, which was discovered in 1997, is unknown. Here we evaluate the available data on human UCP3 expression and show that UCP3 is up-regulated in situations where fatty acid delivery to the mitochondria exceeds oxidative capacity, whereas down-regulation of UCP3 is observed when oxidative capacity is enhanced. With a surplus of fatty acid delivery, accumulation of nonesterified fatty acids in the cytoplasm is likely to occur. Although the inner mitochondrial membrane provides a barrier for nonesterified fatty acids, neutral nonesterified fatty acids can partition into the phospholipid bilayer and flip-flop to the other side of the membrane, where they can be released into the mitochondrial matrix. Due to pH differences, these nonesterified fatty acids will be protonated. Because fatty acid anions can neither be metabolized inside the matrix or cross the inner mitochondrial membrane, accumulation of nonesterified fatty acids inside the matrix might occur. Therefore, we postulate that UCP3 is required for the outward translocation of fatty acids from the mitochondrial matrix. In this way, UCP3 is involved in the protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix.

Animals↗
PubMed2001

Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes.

Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin levels. However, data regarding the expression of UCP3 in patients with type 2 diabetes is inconsistent, and so far, there have been no reports of UCP3 protein content. Here we compared, for the first time, the protein levels of UCP3 in vastus lateralis muscle in 14 male type 2 diabetic patients (age 49.8 +/- 2.1 years; BMI 27.2 +/- 1.2 kg/m(2); mean +/- SE) with 16 male control subjects (age 48.0 +/- 1.9 years; BMI 23.4 +/- 0.6 kg/m(2)). We found that UCP3 protein levels were twice as low in patients with type 2 diabetes compared with control subjects (117 +/- 16 vs. 58 +/- 12 AU; P = 0.007). There was no correlation between UCP3 content and BMI. In conclusion, UCP3 content is lower in type 2 diabetic patients compared with healthy control subjects. These results are consistent with a role for UCP3 in glucose homeostasis and suggest a role for UCP3 in type 2 diabetes.

Blood Glucose↗
PubMed2000

GLUT-4 expression is not consistently higher in type-1 than in type-2 fibres of rat and human vastus lateralis muscles; an immunohistochemical study.

In whole muscle homogenates, the glucose transporter-4 (GLUT-4) content is reported to be higher in muscles consisting predominantly of oxidative (type-1) muscle fibres than in muscles consisting predominantly of glycolytic (type-2) fibres. From these findings, it has been deduced that in rat muscle, oxidative fibres have an intrinsically higher level of GLUT-4 protein than glycolytic fibres. No data is available concerning human muscle. Moreover, the fibre-type-specific expression of GLUT-4 has not yet been examined directly. In this study, the relative abundance of GLUT-4 protein expression in individual fibres of different types within a muscle was compared directly in immunohistochemical assays. The human vastus lateralis muscle and a selection of rat muscles were studied using a novel GLUT-4 antiserum. It is concluded that the pattern of fibre-type-specific GLUT-4 expression differs between human and rats and varies between the different muscles studied, indicating that non-fibre-type-specific factor(s) affect expression of GLUT-4. The observation that within a muscle a fibre-type-specific expression of GLUT-4 was observed indicates that fibre-type-specific factors contribute to GLUT-4 expression as well. Thus, it can be postulated that both fibre-type-dependent and fibre-type-independent factors affect GLUT-4 expression.

Animals↗
PubMed2000

Controlled lengthening or shortening contraction-induced damage is followed by fiber hypertrophy in rat skeletal muscle.

To study the hypothesis that more severe damage, caused by controlled lengthening (L) contractions, results in greater myofiber hypertrophy compared to increase in fiber size followed shortening (S) contractions, tibialis anterior muscles of anesthesized male Wistar rats were subjected to 240 either L or S contractions. The highest increase in muscle beta-glucuronidase activity, an indicator of muscle damage, was observed in L (7.1-fold) 4 days and in S (2.6-fold) 8 days postexercise. Dystrophin- and desmin-negative as well as fibronectin-positive fibers (signs of the early phase of damage) were observed immediately after exercise in the L group. At 4 days, massive myofiber injury was visible, and internally localized nuclei were present at 15-80 days after exercise in the L group. The shift towards more glycolytic fiber types (p<0.05 in L and S) and an increased mean cross-sectional area of type IIX/B fibers (p < 0.001 in L and S) at 80 days were observed in both groups. The observed minor damage with unchanged myofiber structures following S induced, however, an increase in myofiber cross-sectional area of nearly the same magnitude as that following L, which was more damaging. The results do not support the hypothesis that fiber hypertrophy depends on the extent of the myofiber damage upon the exercised muscles.

Animals↗
PubMed1999

Enzyme activity of rat tibialis anterior muscle differs between treatment with triamcinolone and prednisolone and nutritional deprivation.

The maximal activity of a selection of enzymes involved in muscle carbohydrate handling, citric acid cycle and fatty acyl beta-oxidation were studied after treatment with the fluorinated corticosteroid triamcinolone and compared to a similar treatment of the non-fluorinated corticosteroid prednisolone in an equipotent anti-inflammatory dose. Furthermore, because triamcinolone causes loss of body mass and muscle wasting, the effects of triamcinolone were investigated relative to a control group, with the same loss of body mass, due to nutritional deprivation. The study was performed in male Wistar rats in the following treatment groups: TR, triamcinolone treatment (0.25 mg x kg(-1) x day(-1) for 2 weeks), which resulted in a reduction of body mass (24%); ND, nutritional deprivation (30% of normal daily food intake for 2 weeks) resulting in a similar (24%) decrease of body mass as TR; PR, prednisolone treatment (0.31 mg x kg(-1) x day(-1) for 2 weeks), with a 10% increase in body mass; FF, free-fed control group, with a 12% increase in body mass in 2 weeks. Compared to FF, TR induced an increase in phosphofructokinase (PFK) activity (P < 0.01), glycogen synthase [GS(i + d)] activity (P < 0.05) and glycogen content (P < 0.01) in the tibialis anterior muscle. The PR and ND caused no alterations in PFK or citrate synthase (CS) activity compared to FF. Compared to PR, TR induced an increase in PFK (P < 0.01), CS (P < 0.05) and GS(i + d) activity (P < 0.01). Both TR and PR caused an increased muscle glycogen content, being more pronounced in TR (P < 0.05). Compared to ND, TR induced an increased CS (P < 0.05) and GS(i + d) activity (P < 0.01) and glycogen content (P < 0.01). The ND resulted in a decreased glycogen content compared to FF (P < 0.05). None of the treatments affected the activity of glycogen phosphorylase, beta-hydroxyacyl coenzyme A dehydrogenase and lactate dehydrogenase. It was concluded that corticosteroids led to an increased muscle glycogen content; however, the changes in the enzymes of carbohydrate metabolism were corticosteroid type specific and did not relate to undernutrition, which accompanied the triamcinolone treatment.

Animals↗
PubMed1998

The disruption of myofibre structures in rat skeletal muscle after forced lengthening contractions.

Specific antibodies against structural proteins (actin, desmin, dystrophin, fibronectin) of muscle fibres were used to study the effect of forced lengthening contractions on muscle microarchitecture. Tibialis anterior (TA) muscle of male Wistar rats were subjected to 240 forced lengthening contractions. At consecutive time points (0, and 6 h, 2, 4, and 7 days) after stimulation, the TA muscle was excised for biochemical and histological assays. Beta-Glucuronidase activity, a quantitative indicator of muscle damage, showed increased values 2-7 days after the lengthening, peaking on day 4 (11.7-fold increase). A typical course of histopathological changes (myofibre swelling, necrosis and regeneration) was observed. In immunohistochemistry, the earliest abnormality observed was discontinuous dystrophin staining in some swollen fibres immediately after commencement of exercise, while at the same time no alterations occurred in the staining of the other antibodies studied. Six hours later, all the swollen fibres were uniformly desmin as well as dystrophin negative. The great majority, but not all, of the swollen fibres showed disorganized actin staining and intramyocellular localization of fibronectin. The early phase disruption of myofibre structures as measured in this study provides evidence of their central role following damage in skeletal muscle. These results suggest that the sequence of structural changes in the route to muscle fibre necrosis in injury induced by forced lengthening contraction originates in the disruption of the plasma membrane and the intermediate filament, which leads to disturbances in the myofibrillar system.

Actins↗
PubMed1998

Acute and sustained effects of isometric and lengthening muscle contractions on high-energy phosphates and glycogen metabolism in rat tibialis anterior muscle.

Previous studies have shown that lengthening contractions, in contrast to isometric contractions, readily result in sustained malfunctioning of the exercised muscles. The present study was performed to investigate whether an exercise period with many (240) lengthening contractions (LC) results in alterations in muscle high-energy phosphates and inosine monophosphate (IMP) content, different from muscles performing a few (60) lengthening or a few (60) or many (240) isometric contractions (IC). Moreover, we sought for a possible cause(s) of the inability to replenish muscle glycogen stores following LC. Rat tibialis anterior muscles were subjected in vivo to either 60 or 240 LC or IC. Structural muscle damage occurred only after 240 LC. The fact that tissue glycogen levels declined to a similar extent during LC and IC suggests that the energy demand was comparable during both types of exercise. Nevertheless, the observation that on the one hand tissue stores of adenine nucleotides showed a greater decline, and on the other hand the tissue content of IMP increased to a significantly higher level after LC than after IC, clearly indicates that muscle energy metabolism is more disturbed during LC than during IC. The high tissue levels of IMP may contribute to impaired mechanical function as previously observed in muscles subjected to LC. In contrast to 240 IC, 24 hours after 240 LC, tissue glycogen stores and high-energy phosphate levels were not restored to control values. The present findings indicate that depressed glycogen synthase activity and impaired activity of the mitochondrial marker enzyme cytochrome C oxidase probably contribute to a continuous disturbance of energy metabolism in the exercised muscles during the 24 hours following 240 LC.

Adenosine Diphosphate↗
PubMed1997

Contraction failure of skeletal muscle of rats recovering from critical illness.

1. Most patients recovering from critical illness experience enhanced fatiguability. Previously we have shown that zymosan-induced critical illness in rats is attended by a decreased mitochondrial content (maximal aerobic capacity) in skeletal muscle. We investigated whether this decrease results in an increased reduction in high-energy phosphates and a subsequent loss of contractility during in situ electrical stimulation in rats recovering from zymosan treatment. 2. Plantar-flexor muscles of the hindlimb were electrically stimulated via the innervating nerve to develop maximal isometric tetanic contraction. 3. Decreased concentrations of ATP were measured in gastrocnemius muscle of zymosan-treated rats, both at rest and after stimulation, in comparison with ad libitum-fed and pair-fed control rats. However, no differences in the stimulation-induced decreases in high-energy phosphate levels and changes in other metabolites, except ADP, were observed between the groups. Tension development in the zymosan-treated rats was, however, about 85% less compared with the pair-fed controls during the whole stimulation period. 4. We conclude that the primary cause of the loss of muscle tension in zymosan-treated rats is an insensitivity of skeletal muscle to stimulation via the nerve. An additional derangement in ATP production is, however, indicated by the comparable decreases in energy substrates during development of a dramatically lower tension.

Adenosine Triphosphate↗
PubMed1997

The Conconi test.

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Anaerobic Threshold↗
PubMed1996

Structural muscle damage and muscle strength after incremental number of isometric and forced lengthening contractions.

Exercise-induced muscle damage is characterized by histological changes, like Z-line streaming, inflammatory response and decreased muscle function reflected in a prolonged decline in maximal isometric muscle strength after eccentric work. It is assumed that force decrement is mainly related to the amount of structural damage. However, the relationship between number of eccentric contractions, magnitude of structural damage and force decrement is not very well documented. Therefore we studied the effect of an increasing number of both isometric and eccentric (forced lengthening) contractions on histological parameters of muscle damage and maximal isometric force in an experimental in situ rat model. Tibialis anterior muscles of male Wistar rats were subjected to an increasing number of either isometric or eccentric contractions and were examined for histological markers of muscle damage. The present study shows that muscle damage increases progressively with the number of forced lengthening contractions. Maximal isometric torque was found to decline after both types of exercise. However, the decline after forced lengthening exercise was more pronounced. Only a weak relationship between percentage of histological muscle damage and isometric torque after forced lengthening contractions was found. The findings of the present study suggest that the decline in muscle force after eccentric exercise may partly be attributed to other factors than structural damage.

Analysis of Variance↗
PubMed1994

Overtraining--what do lactate curves tell us?

In a cyclist, competing at national and international level, submaximal lactate concentrations were initially interpreted as improved endurance capacity. However, 2 weeks later, a test in which maximal lactate was measured showed that maximal lactate was decreased as well. Together with the complaints of deteriorating performance and subjective complaints of irritability and sleep disturbances, overtraining was diagnosed. After decreasing the training load, performance was gradually restored. This example indicates that athletes should be carefully questioned on their ability to perform their regular training programme, their motivation, possible sleeping disorders and eating problems. This case serves as a reminder to interpret lactate curves carefully and shows how important it is to obtain maximal lactate from a graded exercise test.

Adult↗
PubMed1993

A physiological/psychological indicator of over-reaching during intensive training.

Many indicators of over-reaching and over-training have been proposed, using both physiological and psychological techniques. Field testing of athletes has led us to believe that a decrease in the ratio of blood lactate concentration to ratings of perceived exertion indicates a fatigued and/or over-reached state following intensive training. The purpose of this study, therefore, was to test the hypothesis that a decrease in the ratio of blood lactate concentration to ratings of perceived exertion would indicate an over-reached state. Seven well-trained male cyclists performed two weeks each of: normal (moderate) training, overtraining and recovery. During each time period an incremental exercise test was performed to maximal effort with blood lactate concentration (HLa) and ratings of perceived exertion (RPE) obtained for each workload. All seven subjects became over-reached during the two week period of intensive interval training. The ratio of HLa:RPE (multiplied by 100) decreased with all workloads following both one (mean decrease 29.1 +/- 3.0%) and two (mean decrease 48.7 +/- 2.5%) weeks of overtraining. However, only the decrease at the maximal workload was statistically significant. Examining the individual data revealed that at maximal workload all seven subjects had HLa:RPE ratios of less than 100 when over-reached. The ease and speed at which the HLa:RPE ratio can be determined may make it useful for coaches and athletes in monitoring intensive exercise training and recovery.

Adult↗
PubMed1992

Physiological changes in male competitive cyclists after two weeks of intensified training.

To study the physiological response to heavy training, seven male competitive cyclists intensified their normal training program for two weeks (IIT) in order to achieve a state of short-term overtraining. The subjects underwent a graded cycle ergometer test to exhaustion, an outdoor 8.5 km time trial and a computerized test to study reaction time and visual perception, before, during and after the two weeks of intensified training and after two weeks of recovery. Furthermore subjects kept a daily log in the form of a questionnaire. After two weeks of IIT all subjects showed symptoms of overtraining: the general state of well being declined as indicated by the questionnaire while performances on time trial (mean +/- SEM: 830 +/- 14 sec-871 +/- 19 sec), contests and maximal power output (mean +/- SEM: 336 7 watt-310 +/- 5 watt) declined significantly. Maximal (mean +/- SEM 11.8 +/- 1.1 mmol.l-1-5.9 +/- 0.5 mmol.l-1) and submaximal lactate values were significantly lowered during ergometer test after the IIT, while the workload at the 4 mmol point increased significantly (mean +/- SEM 234 +/- 10 watt-267 +/- 13 watt). Sleeping heart rate increased significantly (mean +/- SEM 49.5 +/- 9.3 BPM-54.3 +/- 8.8 BPM). Maximal heart rate (mean +/- SEM 185 +/- 3 BPM-178 +/- 2 BPM, mean heart rate during the time trial (mean +/- SEM 178 +/- 2 BPM-169 +/- 2 BPM) and VO2max (mean +/- SEM 4801 +/- 121 ml.min-1-4409 +/- 101 ml.min-1) were all significantly lowered by the IIT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗