RESUMO
Intramyocellular lipid content (IMCL) serves as a good biomarker of skeletal muscle insulin resistance (IR). However, intracellular fatty acid metabolites [malonyl-CoA, long-chain acyl-CoA (LCACoA)] rather than IMCL are considered to be responsible for IR. This study aimed to investigate dynamics of IMCL and fatty acid metabolites during fed-to-starved-to-refed transition in lean and obese (IR) Zucker diabetic fatty rats in the following different muscle types: soleus (oxidative), extensor digitorum longus (EDL, intermediary), and white tibialis anterior (wTA, glycolytic). In the fed state, IMCL was significantly elevated in obese compared with lean rats in all three muscle types (soleus: 304%, EDL: 333%, wTA: 394%) in the presence of elevated serum triglycerides but similar levels of free fatty acids (FFA), malonyl-CoA, and total LCACoAs. During starvation, IMCL in soleus remained relatively constant, whereas in both rat groups IMCL increased significantly in wTA and EDL after comparable dynamics of starvation-induced FFA availability. The decreases of malonyl-CoA in wTA and EDL during starvation were more pronounced in lean than in obese rats, although there were no changes in soleus muscles for both groups. The concomitant increase in IMCL with the fall of malonyl-CoA support the concept that, as a reaction to starvation-induced FFA availability, muscle will activate lipid oxidation more the lower its oxidative capacity and then store the rest as IMCL.
Assuntos
Ácidos Graxos/metabolismo , Resistência à Insulina/fisiologia , Músculo Esquelético/metabolismo , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/fisiologia , Ácidos Graxos/análise , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos Insaturados/análise , Técnica Clamp de Glucose , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Glicogênio Fosforilase/metabolismo , Hexoquinase/metabolismo , Insulina/sangue , Corpos Cetônicos/sangue , Lipídeos/análise , Masculino , Malonil Coenzima A/metabolismo , Fibras Musculares de Contração Rápida/química , Fibras Musculares de Contração Rápida/enzimologia , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Lenta/química , Fibras Musculares de Contração Lenta/enzimologia , Fibras Musculares de Contração Lenta/metabolismo , Músculo Esquelético/química , Músculo Esquelético/enzimologia , Ratos , Ratos Zucker , Triglicerídeos/sangueRESUMO
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 (1)H-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.
