Decreased muscle acetyl-coenzyme A carboxylase 2 mRNA and insulin resistance in formerly obese subjects.

Abstract

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.

RESEARCH METHODS AND PROCEDURES:

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.

DISCUSSION:

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.

• Authors: Giuseppina Rosa, Melania Manco, Natalie Vega, Aldo V Greco, Marco Castagneto, Hubert Vidal, Geltrude Mingrone
• Journal: Obesity research (Obes Res) Vol. 11 Issue 11 Pg. 1306-12 (Nov 2003) ISSN: 1071-7323 [Print] United States
• PMID: 14627750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Isoenzymes
• RNA, Messenger
• Triglycerides
• Malonyl Coenzyme A
• Acetyl-CoA Carboxylase

Topics

• Acetyl-CoA Carboxylase (genetics)
• Biliopancreatic Diversion
• Biopsy
• Body Composition
• Fasting
• Female
• Glucose Clamp Technique
• Humans
• Insulin (blood)
• Insulin Resistance
• Isoenzymes (genetics)
• Male
• Malonyl Coenzyme A (metabolism)
• Muscle, Skeletal (chemistry, enzymology)
• Obesity, Morbid (enzymology, surgery)
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Triglycerides (analysis)
• Weight Loss