Muscle-Type Specific Intramyocellular and Hepatic Lipid Metabolism During Starvation in Wistar Rats
- Claudia Neumann-Haefelin,
- Anja Beha,
- Johanna Kuhlmann,
- Ulrich Belz,
- Martin Gerl,
- Manfred Quint,
- Gabriele Biemer-Daub,
- Mark Broenstrup,
- Marion Stein,
- Elke Kleinschmidt,
- Hans-Ludwig Schaefer,
- Dieter Schmoll,
- Werner Kramer,
- Hans-Paul Juretschke and
- Andreas W. Herling
- Address correspondence and reprint requests to Dr. Andreas W. Herling, Disease Group Metabolic Diseases Pharmacology, H 815/H 821, Aventis Pharma Deutschland, Industriepark Hoechst, 65926 Frankfurt/Main, Germany. E-mail: andreas.herling{at}aventis.com
Abstract
The physiological dynamics of intramyocellular lipids (IMCLs) in different muscle types and of hepatocellular lipids (HepCLs) are still uncertain. The dynamics of IMCLs in the soleus, tibialis anterior, and extensor digitorum longus (EDL) muscles and HepCL during fed, 12- to 72-h starved, and refed conditions were measured in vivo by 1H-magnetic resonance spectroscopy (MRS) in Wistar rats. Despite significant elevations of free fatty acids (FFAs) during starvation, HepCLs and IMCLs in soleus remained constant. In tibialis anterior and EDL, however, IMCLs increased significantly by 170 and 450% after 72 h of starvation, respectively. After refeeding, elevated IMCLs dropped immediately in both muscles. Total muscle long-chain acyl-CoAs (LCACoAs) remained constant during the study period. Hepatic palmitoleoyl-CoA (C16:1) decreased significantly during starvation while total hepatic LCACoAs increased significantly. Consistent with constant values for FFAs, HepCLs, IMCLs, and muscle LCACoAs from 12–72 h of starvation, insulin sensitivity did not change. We conclude that during starvation-induced adipocytic lipolysis, oxidative muscles dispose elevated FFAs by oxidation, while nonoxidative ones neutralize FFAs by reesterification. Both mechanisms might prevent impairment of insulin signaling by maintaining low levels of LCACoAs. Hepatic palmitoleoyl-CoA might have a special role in lipid metabolism due to its unique dynamic profile during starvation.
- EDL, extensor digitorum longus
- EGP, endogenous glucose production
- FFA, free fatty acid
- HepCL, hepatocellular lipid
- HPLC, high-performance liquid chromatography
- IMCL, intramyocellular lipid
- LCACoA, long-chain acyl-CoA
- MRS, magnetic resonance spectroscopy
- RSD, relative standard deviation
- SCD, stearoyl-CoA desaturase
- tCr, total creatine
Footnotes
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C.N.-H. and A.B. contributed equally to this study.
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- Accepted October 17, 2003.
- Received July 10, 2003.
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