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Sex differences in body composition but not neuromuscular function following long-term, doxycycline-induced reduction in circulating levels of myostatin in mice.

ABSTRACT: Age-related declines in muscle function result from changes in muscle structure and contractile properties, as well as from neural adaptations. Blocking myostatin to drive muscle growth is one potential therapeutic approach. While the effects of myostatin depletion on muscle characteristics are well established, we have very little understanding of its effects on the neural system. Here we assess the effects of long-term, post-developmental myostatin reduction on electrophysiological motor unit characteristics and body composition in aging mice. We used male (N = 21) and female (N = 26) mice containing a tetracycline-inducible system to delete the myostatin gene in skeletal muscle. Starting at 12 months of age, half of the mice were administered doxycycline (tetracycline) through their chow for one year. During that time we measured food intake, body composition, and hindlimb electromyographic responses. Doxycycline-induced myostatin reduction had no effect on motor unit properties for either sex, though significant age-dependent declines in motor unit number occurred in all mice. However, treatment with doxycycline induced different changes in body composition between sexes. All female mice increased in total, lean and fat mass, but doxycycline-treated female mice experienced a significantly larger increase in lean mass than controls. All male mice also increased total and lean mass, but administration of doxycycline had no effect. Additionally, doxycycline-treated male mice maintained their fat mass at baseline levels, while the control group experienced a significant increase from baseline and compared to the doxycycline treated group. Our results show that long-term administration of doxycycline results in body composition adaptations that are distinctive between male and female mice, and that the effects of myostatin reduction are most pronounced during the first three months of treatment. We also report that age-related changes in motor unit number are not offset by reduced myostatin levels, despite increased lean mass exhibited by female mice.

SUBMITTER: Tavoian D

PROVIDER: S-EPMC6872155 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Sex differences in body composition but not neuromuscular function following long-term, doxycycline-induced reduction in circulating levels of myostatin in mice.

Tavoian Dallin D Arnold W David WD Mort Sophia C SC de Lacalle Sonsoles S

PloS one 20191121 11

Age-related declines in muscle function result from changes in muscle structure and contractile properties, as well as from neural adaptations. Blocking myostatin to drive muscle growth is one potential therapeutic approach. While the effects of myostatin depletion on muscle characteristics are well established, we have very little understanding of its effects on the neural system. Here we assess the effects of long-term, post-developmental myostatin reduction on electrophysiological motor unit ...[more]

PMID: 31751423

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Project description:BackgroundLow bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU).ObjectiveTo determine if there are differences in BMD and body composition between male and female participants with PKU.MethodsFrom our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15-50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16-35 y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1-3 weeks each.ResultsMale participants had significantly lower mean total body BMD Z-scores (means ± SE, males = - 0.9 ± 0.4; females, 0.2 ± 0.3; p = 0.01) and tended to have lower mean L1-4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above - 1.0 compared to 100% of females (p = 0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r = - 0.58; p = 0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means ± SE, males: 67 ± 6 g, females: 52 ± 4 g; p = 0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339 ± 75 mg/d, females: 228 ± 69 mg/d; p = 0.13). Females had a greater percentage of total fat mass compared to males (means ± SE, males: 24.5 ± 4.8%, females: 36.5 ± 2.5%; p = 0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index.ConclusionsMales with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258.

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Dataset Information

Sex differences in body composition but not neuromuscular function following long-term, doxycycline-induced reduction in circulating levels of myostatin in mice.

Publications

Sex differences in body composition but not neuromuscular function following long-term, doxycycline-induced reduction in circulating levels of myostatin in mice.

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