title: Muscle type-specific fatty acid metabolism in insulin resistance: an integrated in vivo study in Zucker diabetic fatty rats.
abstract: 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.
authors.affiliation: Sanofi-Aventis Deutschland, Frankfurt/Main, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Beha
authors.forename: Hans-Paul
authors.initials: HP
authors.lastname: Juretschke
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuhlmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Neumann-Haefelin
authors.forename: Ulrich
authors.initials: U
authors.lastname: Belz
authors.forename: Martin
authors.initials: M
authors.lastname: Gerl
authors.forename: Werner
authors.initials: W
authors.lastname: Kramer
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Herling
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D015309:Glucose Clamp Technique; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007657:Ketone Bodies / Q000097:blood; D008055:Lipids / Q000032:analysis; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D007657:Ketone Bodies; D008055:Lipids; D014280:Triglycerides; D008316:Malonyl Coenzyme A; D015094:3-Hydroxyacyl CoA Dehydrogenases; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D024981:Glycogen Phosphorylase; D006593:Hexokinase