University of Illinois Urbana-Champaign

Altering Muscle Hypertrophy and Fat Accumulation in Myostatin Null Mice

Dilger, Anna C.

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1_Dilger_Anna.pdf

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https://hdl.handle.net/2142/14555

Description

Title
Altering Muscle Hypertrophy and Fat Accumulation in Myostatin Null Mice
Author(s)
Dilger, Anna C.
Issue Date
2010-01-06T16:12:00Z
Director of Research (if dissertation) or Advisor (if thesis)
Killefer, John
Doctoral Committee Chair(s)
Killefer, John
Committee Member(s)
  • McKeith, Floyd K.
  • Novakofski, Jan
  • Layman, Donald K.
Department of Study
Animal Sciences
Discipline
Animal Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2010-01-06T16:12:00Z
Keyword(s)
  • muscle
  • Fat
  • myostatin
  • mice
Abstract
Myostatin is a negative regulator of muscle growth. Loss of myostatin function results in a dramatic phenotype in several species including cattle, mice, dogs and humans. Myostatin mutants exhibit wide-spread hypermuscularity and decreased fat accumulation. Though the phenotype of myostatin mutant animals is very striking, the question remains whether the loss of myostatin function fundamentally changes growth potential, metabolism, or inherent regulation in tissues, or if it is simply an effect independent of other factors. To that end, we sought to increase muscle growth even further in myostatin null mice through the use of the β-adrenergic agonist clenbuterol. The effects of clenbuterol treatment and the loss of myostatin function are quite similar and, in this study, were completely additive. Clenbuterol treatment increased muscle weights and protein accretion and reduced fat accumulation in both wild type and myostatin null mice. There was a significant interaction of genotype and clenbuterol treatment for gastrocnemius muscle weight, but the magnitude of the differences in weight gain between myostatin null and wild type was very small. We also aimed to alter fat accumulation and metabolism in myostatin null mice by feeding diets high in fat. Other research indicated that myostatin null mice were resistant to fat accumulation induced by high-fat feeding. In our study, fat accumulation was increased in both wild type and myostatin null mice fed high-fat diets, but the magnitude of the increase in myostatin null mice was less than that of wild type mice. This suggests that myostatin null mice are partially resistant to high-fat diet-induced obesity. Markers of metabolic syndrome often induced by high-fat feeding in mice were also improved in myostatin null compared with wild type mice. Liver fat content, serum triglycerides and serum leptin levels were lower in high-fat fed myostatin null mice than similarly fed wild type mice. Glucose tolerance, however, was altered in both genotypes by high-fat feeding and did not show an improvement in myostatin null mice. Given the partial resistance to high-fat induced fat accumulation, we investigated expression of adaptive thermogenic genes and found that some genes were upregulated specifically in high-fat fed myostatin null mice. These changes, however, likely do no fully account for the resistance to fat gain in myostatin null mice. Overall, we conclude from these two studies that, while the loss of myostatin function does have a dramatic effect in increasing muscle growth and reducing fat deposition, it does not represent maximal muscle or minimal fat accumulation. Muscle and fat tissues do respond to both beta-adrenergic agonists and to increased dietary fat and calories.
Graduation Semester
2009-12
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http://hdl.handle.net/2142/14555
Copyright and License Information
Copyright 2009 Anna C. Dilger

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