Abstract
The effect of muscle fiber type and maturation on intramyocellular lipid (IMCL) content
and its relationship to insulin resistance was investigated. Intramyocellular lipid
content in slow-twitch (soleus) and fast-twitch (tibialis anterior, TA) muscles of
fa/fa (Zucker fatty rat, ZFR) and age-matched lean (Zucker lean rat, ZLR) Zucker rats were
repeatedly measured over 3 months. Intramyocellular lipid levels in both the soleus
and the TA were significantly higher in the ZFR relative to the ZLR. For the ZFR,
IMCLTA increased by ~2-fold from 5.3 to 8.4 weeks of age. No subsequent accumulation of
IMCLTA occurred in ZFR from 8.4 up to 13.1 weeks of age. For ZLR, IMCLTA contents steadily decreased from 6.6 to 13.1 weeks of age (−77%, P < .05). In contrast, IMCL levels in the soleus were not significantly altered in
either rat strain over the course of the study. Maximum impairment in whole-body insulin
sensitivity in ZFR was observed at 9-weeks of age, concomitant with peak IMCLTA accumulation. Insulin-stimulated 2-deoxy-d-glucose (2DG) transport in the TA muscle of 10.2- and 14.1-week-old ZFR was significantly
impaired relative to age-matched ZLR. Insulin-stimulated glucose uptake in the soleus
of ZFR and ZLR decreased (P < .05) as the animals matured (ZFR, −49%; ZLR, −69%). Overall, these results support
the hypothesis that fast-twitch glycolytic muscles play a major role during the onset
of insulin resistance. In addition, proper timing may govern the success of a pharmacological
studies aimed at measuring the impact of insulin-sensitizing drugs on IMCL.
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Article info
Publication history
Accepted:
November 29,
2004
Received in revised form:
November 29,
2004
Received:
November 21,
2004
Identification
Copyright
© 2005 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
