Increase In Proportion Of Type Research Articles

Motoneuron activity and muscle fibre type composition in hemiparesis

The firing of single motor units (MUs) in musculus tibialis anterior (TA) was studied during maximal voluntary effort and maximal speed of walking in 10 patients with severe chronic hemiparesis and the findings compared to normal data. As shown in a previous study, the paralysed TA exhibited an increase in proportion of type 2 fibres as compared with normal muscle. Thus, 57% of the muscle fibres were type 1 and 43% type 2, while the normal percentages were 80% and 20% respectively. The present findings indicate that in the paralysed muscles a little less than half of the fibres, i.e. roughly the equivalent of the type 2 population, was not tonically active either during sustained voluntary contraction or during locomotion. Normally high threshold MUs reached high rates during both modes of activation. The findings paralysed muscles also indicate that a little more than half of the fibres, i.e. roughly the equivalent of the type 1 population, could be brought into tonic firing during voluntary contraction as well as during walking. Their maximal firing rate was, however, no more than two thirds of that of normal low threshold MUs.

Developmental Programming: Role of Androgen and Insulin in Advancing Placentome Differentiation in Testosterone-Treated Sheep.

Testosterone (T) administration from gestational days (d) 30-90 induces intra-uterine growth retardation (IUGR), low birth weight, and adult reproductive and metabolic dysfunctions. IUGR was evident in d140 T fetuses, but not in d65 or d90 fetuses. Advanced placental differentiation in T females, which was reflected as an increase in proportion of type C placentomes and their weights during d65 and d90 of gestation, may have overcome IUGR at these fetal ages. Gestational treatment with dihydrotestosterone (DHT), a non-aromatizable androgenic metabolite of T, elicited similar effects at the placental level, suggesting that advanced placental differentiation may be mediated through androgenic programming. Confirmation that DHT effects are mediated by androgenic programming and not estrogenic programming (DHT can be converted to 3β-diol and act via estrogen receptor 2) would require documentation that progression of placental differentiation can be prevented by negating androgen action. Since gestational diabetes and type 1 diabetes induce histological/gross morphological changes in human placenta, it is conceivable that placental effects of T are mediated via changes in insulin sensitivity. We hypothesized that gestational T excess advances placental differentiation via its androgenic action by altering insulin sensitivity. Pregnant Suffolk sheep were administered 1) T propionate (100 mg, twice weekly, i.m.), 2) T plus flutamide, an androgen antagonist (TF; 15 mg/kg/day oral), 3) T plus rosiglitazone, an insulin sensitizer (TR, 8 mg/day oral), or 4) vehicle (n=6-18/group) beginning d30 of gestation. Distribution and weights of placentome types (type A, B, C, D) and placentome efficiency (ratio of fetal to placental weight) were determined. There were no differences in number or weight of placentomes across treatments, although considerable differences existed in the distribution and weights of placentome types. Number and weight of type B placentomes were lower in T animals compared to controls (control vs. T; number: 44 ± 10.6 vs. 12.7 ± 7.6, p<0.05; weight: 333.8 ± 80.6 g vs. 96.9 ± 45.2 g, p<0.05). In contrast, number and weight of type C placentomes were higher in T animals compared to controls (control vs. T; number: 2.2 ± 0.9 vs. 31.8 ± 9.8, p<0.001; weight: 30.1 ± 14.4 g vs. 217.7 ± 70.3 g, p<0.01). There were no differences in type A or D placentomes between control and T groups. Androgen antagonist co-treatment reversed the effects of T on types B and C placentome number and weight. In contrast, co-treatment with insulin sensitizer did not reverse T effects. Paradoxically, number and weight of type D placentomes were higher in TR females compared to controls (control vs. TR; number: 12.3 ± 7.5 vs. 61 ± 18.6, p<0.05; weight: 192 ± 109.4 g vs. 957.5 ± 361.6 g, p<0.05). Placentome efficiency was similar across groups. These findings provide unequivocal evidence that advanced placental differentiation indeed stems from androgenic programming and that this is not mediated via compromised insulin sensitivity. On the contrary, advancement of placental distribution in the TR group suggests an optimal range of insulin sensitivity requirements. Similar placental efficiency across treatment groups is suggestive that advancement in placental differentiation is able to compensate for IUGR at fetal day 90. Supported by NIH P01 HD44232. (poster)

Exercise in a Pill: Feasibility of Energy Expenditure Targets

The possibility of developing a pill to increase energy expenditure is explored by examining the metabolic processes involved. Such a pill should be targeted at organ systems involved in facultative thermogenesis. In rodents, these are brown adipose tissue (BAT) and skeletal muscle. Since BAT-mediated thermogenesis is not available in adult humans, emphasis here is on skeletal muscle. A hypothesis is presented based on three known facts: (1) plasticity of skeletal muscle, with interconversion of fiber types that differ in their fuel efficiency; (2) presence of thyroxine 5'-deiodinase type 2 (TD2) in human skeletal muscle; (3) gradual increase in thermogenesis that occurs during rehabilitation after starvation, probably in muscle. A low capacity thermogenic system, muscle efficiency thermogenesis (MET), is proposed to occur as adipose stores refill during the transition from famine to feasting to obesity. This system involves increased activity of TD2 and a T3-induced increase in proportion of type II fibers, less efficient at rest and during activity. The protective effect of this system is probably overwhelmed by long-term eating in excess of energy needs. Better understanding of the complex remodeling of differentiated muscle fibers in the conversions proposed and of the regulation of TD2 activity in human skeletal muscle may reveal targets for increasing energy expenditure in humans. In addition, the possibility of exploiting the plasticity of the adipose organ, with conversion of white adipocytes in white adipose tissue to atypical brown adipocytes and increasing thermogenesis in them is considered as another potential target for increasing energy expenditure in humans.

Motoneuron activity and muscle fibre type composition in hemiparesis

The firing of single motor units (MUs) in musculus tibialis anterior (TA) was studied during maximal voluntary effort and maximal speed of walking in 10 patients with severe chronic hemiparesis and the findings compared to normal data. As shown in a previous study, the paralysed TA exhibited an increase in proportion of type 2 fibres as compared with normal muscle. Thus, 57% of the muscle fibres were type 1 and 43% type 2, while the normal percentages were 80% and 20% respectively. The present findings indicate that in the paralysed muscles a little less than half of the fibres, i.e. roughly the equivalent of the type 2 population, was not tonically active either during sustained voluntary contraction or during locomotion. Normally high threshold MUs reached high rates during both modes of activation. The findings paralysed muscles also indicate that a little more than half of the fibres, i.e. roughly the equivalent of the type 1 population, could be brought into tonic firing during voluntary contraction as well as during walking. Their maximal firing rate was, however, no more than two thirds of that of normal low threshold MUs.