Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse

Abstract

Background: Knowledge of the morphological and biochemical alterations occurring in skeletal muscles of obese animals is relatively limited, particularly with respect to non-limb muscles and relationship to fibre type. Objective: Sternomastoid (SM; fast-twitch), extensor digitorum longus (EDL; fast-twitch), and soleus (SOL; mixed) muscles of ob/ob mouse (18-22 weeks) were examined with respect to size (mass, muscle mass-to-body mass ratio, cross-sectional area (CSA)), fibre CSA, protein content, myosin heavy chain (MHC) content, MHC isoform (MHC i ) composition, MHC i -based fibre type composition, and lactate dehydrogenase isoenzyme (LDH iso ) composition. Results: Compared with (control) muscles from lean mice, all the three muscles from ob/ob mice were smaller in size (by 13-30%), with SM and EDL being the most affected. The CSA of IIB and IIB þ IID fibres (the predominant fibre types in SM and EDL muscles) was markedly smaller (by B30%) in ob/ob mice, consistent with differences in muscle size. Total protein content (normalised to muscle mass) was significantly lower in EDL (À9.7%) and SOL (À14.1%) muscles of ob/ob mice, but there were no differences between SM, EDL, and SOL muscles from the two animal groups with respect to MHC content (also normalised to muscle mass). Electrophoretic analyses of MHC i composition in whole muscle homogenates and single muscle fibres showed a shift towards slower MHC i content, slower MHC i containing fibres, and a greater proportion of hybrid fibres in all the three muscles of ob/ob mice, with a shift towards a more aerobic-oxidative phenotype also observed with respect to LDH iso composition. Conclusion: This study showed that SM, EDL, and SOL muscles of ob/ob mice display size reductions to an extent that seems to be largely related to fibre type composition, and a shift in fibre type composition that may result from a process of structural remodelling, as suggested by the increased proportion of hybrid fibres in muscles of ob/ob mice.

Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue

“…Thus, the decreased plasma oxytocin together with reduced OXTR in the skeletal muscle of Zucker fatty rats may contribute to reduced muscle mass (Kemp et al 2009) and the reduced muscle glucose disposal observed in obesity and insulin resistance (King et al 1992). Based on muscle OXTR protein data and muscle membrane oxytocinase activity, we conclude that there is reduced oxytocin processing in the tissue under the conditions of obesity.…”

Obesity and related consequences to ageing

“…There is confusion on how to interpret changes in lean mass associated with muscle separately from non-muscle fat-free mass, that is, liver, intestine, kidney, and heart, which indeed might be enlarged with the development of obesity (Masgrau et al 2012). Studies on rodents demonstrated that muscle mass was not changed under conditions of DIO (Chanseaume et al 2007), whereas reduced muscle mass was found in genetic models of obesity (Kemp et al 2009). In a study of sequential changes of protein synthesis in two types of skeletal muscles during longterm DIO, Masgrau et al (2012) showed that the muscle mass of rats increased in the initial phase (16 weeks fed HFD) and decreased in the second phase (from 16 to 24 weeks fed HFD) of obesity development (Masgrau et al 2012).…”

Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A

“…Importantly, our findings that PGC-1α elevates LDH H and diminishes LDH M subunit expression are further corroborated by mouse and human studies on muscle beds with different fiber type compositions. In fact, fast-twitch muscles, which typically express low levels of PGC-1α, display high amounts of LDH M subunits, whereas the LDH complexes in slow-twitch muscles with higher expression of PGC-1α are enriched in LDH H subunits (38,39).…”