Muscle- and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice

Abstract

The accumulation of certain lipids in non-adipose tissues has been associated with metabolic disorders like insulin resistance and type 2 diabetes. Intracellular lipid pools are highly dynamic and tissue specific. While it is reasonable to expect differences in the regulation of lipid species between organs like liver and muscle, less attention is usually paid to the distinct metabolism of individual skeletal muscles. The plantar flexors gastrocnemius and soleus differ greatly in their content of slow, oxidative fibres, particularly in mice, the most important metabolic animal model. We studied the acute regulation of individual lipid species in these muscles and in the liver by endurance exercise, a strong physiologic modulator of lipid metabolism. Immediately after 1 hour of treadmill running, 13C16-palmitate was applied to trace fatty acid flux and incorporation. Free fatty acids (FFA), acylcarnitines and lipids were quantified by UHPLC-MS. Within 10 min, the tracer was detectable in more than 20 lipid and acylcarnitine species, with a striking incorporation into hepatic triglycerides. The amount of carnitine, FFA, lysolipids and diacylglycerol and the post-exercise increase in short-chain- and acyl-carnitines were pronouncedly higher in soleus than in gastrocnemius. Exercise also caused a significant increase in hepatic carnitine and in the mRNA of the carnitine transporter OCTN2/Slc22a5. The muscle-specific differences can be related to oxidative fibre content and accentuate the need for single-muscle analyses and careful selection of the appropriate muscle in mouse metabolomics experiments. In addition, our results may prompt novel studies on the mechanisms of lipid utilization in liver and muscle.