Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects.
OBJECTIVE
A relationship between free fatty acids, intramuscular triglycerides (TG(M)s), and insulin resistance is widely accepted. The intracellular level of malonyl-coenzyme A (CoA) was suggested to be the possible link. Acetyl-CoA carboxylase (ACC) is a key enzyme in fatty acid metabolism, catalyzing the synthesis of malonyl-CoA, a fatty acid acyl-chain elongation unit, from acetyl-CoA. We assessed ACC2 mRNA expression variations in skeletal muscle of subjects who have undergone biliopancreatic diversion (BPD) operation. BPD, in fact inducing a massive lipid malabsorption, leads to a reversion of insulin resistance.


METHODS
Twelve obese women (BMI > 40 kg/m(2)) were enrolled in the study. Body composition, euglycemic-hyperinsulinemic clamp, and muscle biopsies for lipid analysis and reverse transcription-competitive polymerase chain reaction were performed before and 3 years after BPD.


RESULTS
The average weight loss was around 37%. A significant inverse linear relation was observed between glucose uptake and TG(M) (y = -5.62x - 142.82, R(2) = 0.50, p = 0.01). The reduced amount of ACC2 mRNA directly correlated with both TG(M) (y = 2.11x +69.85, R(2) = 0.70, p = 0.01) and fasting insulin (y = 1.49x + 57.17, R(2) = 0.69, p < 0.01) concentrations.


CONCLUSIONS
In conclusion, down-regulation of ACC2 mRNA, induced by the lowering of plasma insulin concentration, is related to improvement of insulin sensitivity. We hypothesize that reduced amount of malonyl-CoA, consequent to reduced ACC2 mRNA, enhancing fatty acid oxidation, causes lowering of the intramyocitic triglyceride depot.
Rosa
Giuseppina
G
Department of Internal Medicine, Consiglio Nazionale delle Richerche (CNR) Center, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy. giusi_rosa@hotmail.com
Manco
Melania
M
Vega
Natalie
N
Greco
Aldo V
AV
Castagneto
Marco
M
Vidal
Hubert
H
Mingrone
Geltrude
G
D000103:Acetyl-CoA Carboxylase / Q000235:genetics*; D015904:Biliopancreatic Diversion; D001706:Biopsy; D001823:Body Composition; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology*; D009767:Obesity, Morbid / Q000201:enzymology* / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000032:analysis; D015431:Weight Loss
D007328:Insulin; D007527:Isoenzymes; D012333:RNA, Messenger; D014280:Triglycerides; D008316:Malonyl Coenzyme A; D000103:Acetyl-CoA Carboxylase