Myostatin inhibits myogenesis and there is reduced abundance of the mature protein in skeletal muscles of adult male compared with female mice. This reduction probably occurs after translation, which suggests that it is a regulated mechanism to reduce the availability of myostatin in males. Reduced myostatin may, thereby, contribute to the development of sexually dimorphic growth of skeletal muscle. Our first objective was to determine if the decrease in mature myostatin protein occurs before the linear growth phase to aid growth, or afterwards to maintain the mass of adult muscle. Mice were killed from 2 to 32 weeks and the gastrocnemius muscle was excised. Myostatin mRNA increased from 2 to 32 weeks and was higher in males than females (P < 0.001). In contrast, mature protein decreased in males after 6 weeks (P < 0.001). Our second objective was to determine if growth hormone (GH) induces the decrease in mature myostatin protein. GH increased myostatin mRNA and decreased the abundance of mature protein in hypophysectomised mice (P < 0.05). Our final objective was to determine if the decrease in mature protein occurs in skeletal muscles of male Stat5b −/− mice (Stat5b mediates the actions of GH). As expected, mature myostatin protein was not reduced in Stat5b −/− males compared with females. However, myostatin mRNA remained higher in males than females irrespective of genotype. These data suggest that: (1) the decrease in mature myostatin protein is developmentally regulated, (2) GH acting via Stat5b regulates the abundance of mature myostatin and (3) GH acts via a non-Stat5b pathway to regulate myostatin mRNA.
Insulin-like growth factors (IGFs) and myostatin have opposing roles in regulating the growth and size of skeletal muscle, with IGF1 stimulating, and myostatin inhibiting, growth. However, it remains unclear whether these proteins have mutually dependent, or independent, roles. To clarify this issue, we crossed myostatin null () mice with mice overexpressing in skeletal muscle () to generate six genotypes of male mice; wild type ( ), ,, , and Overexpression of increased the mass of mixed fibre type muscles (e.g. ) by 19% over , 33% over and 49% over ( < 0.001). By contrast, the mass of the gonadal fat pad was correspondingly reduced with the removal of and addition of Myostatin regulated the number, while IGF1 regulated the size of myofibres, and the deletion of and independently increased the proportion of fast type IIB myosin heavy chain isoforms in (up to 10% each, < 0.001). The abundance of AKT and rpS6 was increased in muscles of , while phosphorylation of AKT was increased in (, and). Our results demonstrate that a greater than additive effect is observed on the growth of skeletal muscle and in the reduction of body fat when myostatin is absent and IGF1 is in excess. Finally, we show that myostatin and IGF1 regulate skeletal muscle size, myofibre type and gonadal fat through distinct mechanisms that involve increasing the total abundance and phosphorylation status of AKT and rpS6.
The carbon footprint of milk from year-round grazedpasture dairy systems and its variability has had limited research. The objective of this study was to determine temporal, regional, and farm system variability in the carbon footprint of milk from New Zealand (NZ) average dairy production. Farm production and input data were collected from a national database for 2010/11 to 2017/18 across regions of NZ and weighted on relative production supplied to the major dairy cooperative Fonterra to produce an NZ-average. Total greenhouse gas emissions were calculated using a life cycle assessment methodology for the cradle-to-farm gate, covering all on-and off-farm contributing sources. The NZ-average carbon footprint of milk varied from 0.81 kg of CO 2 equivalent (CO 2 eq)/kg of fat-and proteincorrected milk (FPCM) in 2010/11 (with widespread drought) to 0.75 to 0.78 kg of CO 2 eq/kg of FPCM in 2013/14 to 2017/18, with a trend for a small decrease over time. Regional variation occurred with highest carbon footprint values for the Northland region due to greatest climatic and soil limitations on pasture production. Dairy cattle diet was approximately 85% from grazed pasture with up to 15% from brought-in feeds (mainly forages and by-products). The CO 2 emissions from direct fuel and electricity use constituted <2% of total CO 2 eq emissions, whereas enteric methane was near 70% of the total. An estimate of potential contribution from direct land use change (plantation forest to pasture) was 0.13 kg of CO 2 eq/kg of FPCM. This was not included because nationally there has been a net increase in forest land and a decrease in pasture land over the last 20 yr. Data used were highly representative, as evident by the same estimated carbon footprint from 368 farms (in 2017/18) from the national database compared with that from a direct survey of 7,146 farms. New Zealand-specific nitrous oxide emission factors were used, based on many validated field trials and as used in the NZ greenhouse gas inventory, resulting in an 18% lower carbon footprint than if default Intergovernmental Panel on Climate Change factors had been used. Evaluation of the upper and lower quartiles of farms based on per-cow milk production (6,044 vs. 3,542 kg of FPCM/cow) showed a 15% lower carbon footprint for the upper quartile of farms, illustrating the potential for further decrease in carbon footprint with improved farm management practices.
Skeletal muscles of myostatin null (Mstn(−/−)) mice are more susceptible to atrophy during hind limb suspension (HS) than are muscles of wild-type mice. Here we sought to elucidate the mechanism for this susceptibility and to determine if Mstn(−/−) mice can regain muscle mass after HS. Male Mstn(−/−) and wild-type mice were subjected to 0, 2 or 7 days of HS or 7 days of HS followed by 1, 3 or 7 days of reloading (n = 6 per group). Mstn(−/−) mice lost more mass from muscles expressing the fast type IIb myofibres during HS and muscle mass was recovered in both genotypes after reloading for 7 days. Concentrations of MAFbx and MuRF1 mRNA, crucial ligases regulating the ubiquitin-proteasome system, but not MUSA1, a BMP-regulated ubiquitin ligase, were increased more in muscles of Mstn(−/−) mice, compared with wild-type mice, during HS and concentrations decreased in both genotypes during reloading. Similarly, concentrations of LC3b, Gabarapl1 and Atg4b, key effectors of the autophagy-lysosomal system, were increased further in muscles of Mstn(−/−) mice, compared with wild-type mice, during HS and decreased in both genotypes during reloading. There was a greater abundance of 4E-BP1 and more bound to eIF4E in muscles of Mstn(−/−) compared with wild-type mice (P<0.001). The ratio of phosphorylated to total eIF2α increased during HS and decreased during reloading, while the opposite pattern was observed for rpS6. Concentrations of myogenic regulatory factors (MyoD, Myf5 and myogenin) mRNA were increased during HS in muscles of Mstn(−/−) mice compared with controls (P<0.001). We attribute the susceptibility of skeletal muscles of Mstn(−/−) mice to atrophy during HS to an up- and downregulation, respectively, of the mechanisms regulating atrophy of myofibres and translation of mRNA. These processes are reversed during reloading to aid a faster rate of recovery of muscle mass in Mstn(−/−) mice.
Intramuscular injections of the paralytic botulinum neurotoxin A (Btx) and physical exercise are used in the treatment of chronic spasticity in children with cerebral palsy. We tested whether Btx-induced paralysis and/or exercise training would have differential effects on the expression of mechanosensing and signalling genes implicated in the adaptive remodelling of skeletal muscle. Juvenile (29-day-old) male rats were injected with Btx or saline (NoBtx) into the right gastrocnemius and housed in standard cages (NoEx) or with running wheels (Ex), for 3 weeks (n = 6 per group). The mRNA expression of nine sarcomere-associated genes in the medial gastrocnemius was then determined by quantitative reverse transcriptase-polymerase chain reaction. The Btx-injected muscles weighed 50% less than NoBtx muscles, but Ex had no effect on the wet mass of Btx or NoBtx muscles. Atrogenic MuRF1, sarcomeric Titin and myogenic MyoD were upregulated (2-fold) with the elimination of contractile activity in Btx muscle. Expression of CARP, Ankrd2 and MLP was increased with mechanical stimuli associated with Btx (5-to 10-fold) or Ex (2-to 4-fold). Expression of CARP and Ankrd2 increased synergistically in Btx-Ex muscle (≥20-fold), indicating that these genes may be sensitive to passive stretch of the sarcomeric I-band region of titin to which their proteins bind. Tcap, Myopalladin and Atrogin1 were not, or were no longer responsive to the altered mechanical stimuli after 3 weeks of Btx or Ex. The expression of Ankrd2, CARP and MLP may thus be enhanced by passive stretch within the Btx-paralysed and/or exercising gastrocnemius and contribute to adaptations, other than muscle mass, in juvenile rats.
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