MyoD- and nerve-dependent maintenance of MyoD expression in mature muscle fibres acts through the DRR/PRR element

<p>Abstract</p> <p>Background</p> <p>MyoD is a transcription factor implicated in the regulation of adult muscle gene expression. Distinguishing the expression of <it>MyoD </it>in satellite myoblasts and muscle fibres has proved difficult <it>in vivo </it>leading to controversy over the significance of <it>MyoD </it>expression within adult innervated muscle fibres. Here we employ the <it>MD6.0-lacZ </it>transgenic mouse, in which the 6 kb proximal enhancer/promoter (DRR/PRR) of <it>MyoD </it>drives <it>lacZ</it>, to show that MyoD is present and transcriptionally active in many adult muscle fibres.</p> <p>Results</p> <p>In culture, <it>MD6.0-lacZ </it>expresses in myotubes but not myogenic cells, unlike endogenous <it>MyoD</it>. Reporter expression <it>in vivo </it>is in muscle fibre nuclei and is reduced in <it>MyoD </it>null mice. The <it>MD6.0-lacZ </it>reporter is down-regulated both in adult muscle fibres by denervation or muscle disuse and in cultured myotubes by inhibition of activity. Activity induces and represses <it>MyoD </it>through the DRR and PRR, respectively. During the postnatal period, accumulation of β-galactosidase correlates with maturation of innervation. Strikingly, endogenous <it>MyoD </it>expression is up-regulated in fibres by complete denervation, arguing for a separate activity-dependent suppression of <it>MyoD </it>requiring regulatory elements outside the DRR/PRR.</p> <p>Conclusion</p> <p>The data show that <it>MyoD </it>regulation is more complex than previously supposed. Two factors, MyoD protein itself and fibre activity are required for essentially all expression of the 6 kb proximal enhancer/promoter (DRR/PRR) of <it>MyoD </it>in adult fibres. We propose that modulation of MyoD positive feedback by electrical activity determines the set point of <it>MyoD </it>expression in innervated fibres through the DRR/PRR element.</p

Evidence that a maternal "junk food" diet during pregnancy and lactation can reduce muscle force in offspring

Obesity is a multi-factorial condition generally attributed to an unbalanced diet and lack of exercise. Recent evidence suggests that maternal malnutrition during pregnancy and lactation can also contribute to the development of obesity in offspring. We have developed an animal model in rats to examine the effects of maternal overeating on a westernised "junk food" diet using palatable processed foods rich in fat, sugar and salt designed for human consumption. Using this model, we have shown that such a maternal diet can promote overeating and a greater preference for junk food in offspring at the end of adolescence. The maternal junk food diet also promoted adiposity and muscle atrophy at weaning. Impaired muscle development may permanently affect the function of this tissue including its ability to generate force. The aim of this study is to determine whether a maternal junk food diet can impair muscle force generation in offspring. Twitch and tetanic tensions were measured in offspring fed either chow alone (C) or with a junk food diet (J) during gestation, lactation and/or post-weaning up to the end of adolescence such that three groups of offspring were used, namely the CCC, JJC and JJJ groups. We show that adult offspring from mothers fed the junk food diet in pregnancy and lactation display reduced muscle force (both specific twitch and tetanic tensions) regardless of the post-weaning diet compared with offspring from mothers fed a balanced diet. Maternal malnutrition can influence muscle force production in offspring which may affect an individual's ability to exercise and thereby combat obesity

A maternal cafeteria diet during gestation and lactation promotes adiposity and impairs skeletal muscle development and metabolism in rat offspring at weaning

We examined the effects of a maternal cafeteria diet on skeletal muscle and adipose tissue development in the offspring at weaning. Rats born to mothers fed the cafeteria diet either during gestation alone or during both gestation and lactation exhibited a 25% reduction in muscle cross-sectional area with approximately 20% fewer fibres compared with pups fed a balanced chow diet. Maintaining the cafeteria diet during lactation increased intramuscular lipid content and fat pad weights characterized by adipocyte hypertrophy but not hyperplasia. These pups also had elevated muscle IGF-1, IGF-1 receptor, and PPARγ mRNA levels, which may indicate an attempt to maintain normal insulin sensitivity. The increased adiposity and elevated IGF-1, IGF-1 receptor and PPARγ mRNAs were not seen in the pups rehabilitated to the balanced diet during lactation. However, these pups exhibited reduced muscle cell proliferation (PCNA) with reduced insulin receptor and a trend towards reduced glucose transporter (GLUT)-4 mRNAs when compared with pups fed a balanced chow diet, indicating possible alterations in glucose uptake by muscle tissue. Therefore, rats born to mothers fed a cafeteria diet during gestation alone or during both gestation and lactation exhibited impaired skeletal muscle development and metabolic disorders normally associated with insulin resistance as early as the weaning stage