Background: Insulin resistance is associated with impaired mitochondrial function in skeletal
muscle and a potential cause for the adverse effects of diabetes, a well-known risk
factor in cardiac surgery. However, two populations of mitochondria exist in muscle
and it is not known whether both of them are affected equally. We thus aimed to assess
the effect of high fat diet on skeletal muscle interfibrillar (IFM) and subsarcolemmal
(SSM) mitochondria.
Methods: Animals were fed a normal chow (NC) or a high fat diet (HFD) ad libitum. At 13 weeks
of age glucose tolerance and cardiac function were determined. Interfibrillar (IFM)
and subsarcolemmal (SSM) skeletal muscle mitochondria were isolated from the gastrocnemius
muscle and mitochondrial respiratory capacity was assessed.
Results: HFD led to an increase in body weight and to impaired glucose tolerance. Citrate
synthase as an indicator for mitochondrial mass was found increased with HFD (33.3 ± 5.6
vs. 38.4 ± 3.8 U/g organ weight). Respiratory capacity of IFM was compromised with
HFD with glutamate, palmitoyl-carnitine and pyruvate as NADH delivering substrates
(glutamate NC versus HFD: 242 ± 46 versus 123 ± 13 natomsO/min/mg protein). Respiratory
capacity was also reduced with complex II substrate succinate (succinate: 363 ± 52
versus 240 ± 25 natomsO/min/mg protein) and complex IV substrate TMPD ascorbate. ADP
limited respiration was not affected by HFD in IFM. In contrast, subsarcolemmal mitochondria
presented with significantly increased maximal respiratory capacity using fatty acids
as substrate (palmitoyl-carnitine: 77.7 ± 10.8 vs. 137 ± 14). Respiratory capacity
was also increased with the other tested substrates succinate, glutamate, pyruvate/malate
and TMPD ascorbate (TMPD ascorbate: 273 ± 60 versus 632 ± 88 natomsO/min/mg protein).
ADP limited respiration was unaffected in SSM.
Conclusion: The effect of high fat diet on mitochondrial function seems to be strongly influenced
by the localization of mitochondria with an improvement in function at the cell membrane
and a reduction between the myofibrils. This may have functional consequences, as
interfibrillar mitochondria make ATP for contraction.
