Mitochondrial Physiology Network 10.9: 69 (2005) - download pdf

The effect of high-fat feeding on intramuscular lipid and lipid peroxidation levels in UCP3-ablated mice.

Joris Hoeks¹, MKC Hesselink², W Sluiter³, G Schaart², WHM Saris¹, P Schrauwen¹

¹Dept. Human Biology; ²Movement Sciences, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University; ³Dept. Biochemistry, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands. - j.hoeks@hb.unimaas.nl

    Uncoupling protein-3 (UCP3) has been suggested to be involved in the protection against reactive oxygen species (ROS) and ROS-related compounds, such as lipid peroxides. We, specifically, hypothesized that UCP3 is an exporter of fatty acid anions to prevent the accumulation of fatty acids which otherwise are prone to lipid peroxidation by ROS, a feature especially important in situations of lipid oversupply, such as high-fat feeding. The aim of the present study therefore, was to study effect of UCP3 ablation on intramuscular lipid peroxide levels and high-fat diet induced alterations in muscle lipid metabolism.

    UCP3-ablated mice indeed showed ~3-fold higher levels of intramuscular lipid peroxides upon standard chow feeding, compared to their wild-type littermates. Remarkably however, this difference was no longer apparent upon the high-fat diet. The latter finding was accompanied by the finding that, upon HF feeding, intramuscular triacylglycerol (IMTG) levels were ~50% lower in UCP3^-/- mice, in comparison to the UCP3^+/+ animals. Oxidative capacity, measured as succinate dehydrogenase (SDH) activity was however similar between UCP3^-/- and UCP3^+/+ mice. Thus, increased oxidative capacity cannot account for these differences.

    Increased lipid peroxide levels in UCP3-ablated mice supports a role for UCP3 in protecting mitochondria against ROS-induced damage. Upon high-fat feeding, however, other metabolic adaptations seem to be able to protect skeletal muscle from fatty acid accumulation.