The role of muscle fiber types in modulating lean growth

Caiyun Zeng, Purdue University

Abstract

The overall objective of this research was to investigate the role of muscle fiber types in modulating skeletal muscle growth and development. In the first study, we used MyHC IIX- and IIB-null mice to examine clenbuterol-induced skeletal muscle growth. Four-week-old mice were administered with clenbuterol (20 parts per million in drinking water) for 2 weeks. In soleus muscles, which normally contain no IIX or IIB fibers, the hypertrophic effect of clenbuterol was not observed in any genotypes. Further study demonstrated that clenbuterol induced new fiber type formation only in soleus of wild type mice (IIX and IIB fibers) and IIB null (IIX fibers) mice, not in IIX null mice, suggesting that transitional expression of type IIB MyHC depends on the presence of IIX MyHC. Meanwhile, Clenbuterol induced hypertrophy was blunted in fast muscles (gastrocnemius, TA and EDL) of IIX or IIB null mice, demonstrating that the presence of IIX and IIB muscle fibers is essential for clenbuterol-induced skeletal muscle hypertrophy. Finally, the loss of total fiber number contributed to the reduced muscle growth in IIB null mice and clenbuterol failed to rescue this fiber loss. In the second study, we demonstrated that extensor digitorum longus (EDL) and tibialis anterior (TA) muscles in both wild type and IIB null have the same number of muscle fibers at birth, suggesting that loss of IIB MyHC gene does not alter prenatal muscle fiber formation. Although the gastrocnemius muscles in both wild type and IIB null mice have the same amount of muscle fibers at age of 2 weeks postnatal, the gastrocnemius muscle loses almost 50% of total fiber number by 4 weeks of age postnatal and maintains the existing muscle fiber until adult period of life. In the third study, we hypothesized that skeletal muscle specific overexpression of peroxisome proliferator-activated receptor gammar coactivator 1 α (PGC-1α) might rescue loss of total fiber number and subsequent muscle mass by driving formation of slower muscle fibers and/or maintaining integrate neuromuscular junction in gastrocnemius muscle of IIB null mice. The proportion of IIA fibers was increased by 18% at the expense of proportion of IIX fibers when PGC-1α was overexpressed in gastrocnemius of IIB null mice. Moreover, PGC-1α significantly increased total fiber number by 43% in gastrocnemius of IIB null mice. Taken together, IIB muscle fiber is necessary to maintain total fiber number and the subsequent muscle growth, and skeletal muscle specific overexpression of PGC-1α partially rescue the loss of total fiber number in gastrocnemius of IIB null mice. These data reveal new insights into understanding the mechanisms controlling postnatal maintenance of total fiber number in skeletal muscles.^

Degree

Ph.D.

Advisors

David E. Gerrard, Purdue University, Alan Grant, Purdue University.

Subject Area

Agriculture, Animal Culture and Nutrition

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