Skeletal muscle triglycerides lowering is associated with net improvement of insulin sensitivity, TNF-α reduction and GLUT4 expression enhancement.

Autor: Mingrone, G., Rosa, G., Di Rocco, P., Manco, M., Capristo, E., Castagneto, M., Vettor, R., Gasbarrini, G., Greco, A.V.
Předmět:
Zdroj: International Journal of Obesity & Related Metabolic Disorders; Sep2002, Vol. 26 Issue 9, p1165, 8p
Abstrakt: AIMS/HYPOTHESIS: The aim of the present study was to investigate the relationship between intramyocytic triglycerides levels, muscle TNF-α and GLUT4 expression and insulin resistance. METHODS: Insulin sensitivity was studied in 14 severely obese women (BMI > 40 kg/m²), before and 6 months after low-dietary intake or bariatric malabsorptive surgery (bilio-pancreatic diversion, BPD), by the euglycaemic hyperinsulinaemic clamp technique, while the amount of intramyocytic triglycerides was chemically measured in needle muscle biopsies. Using reverse transcriptase-polymerase chain reaction analysis, the muscle mRNA expression of TNF-α and GLUT4 was also investigated. RESULTS: The weight loss after surgery was 25.98 ± 5.81 kg (P < 0.001), while that obtained with the diet was 5.07 ± 5.99 kg (P = NS). Marked decrease in TNF-α mRNA levels (76.67 ± 12.59 to 14.01 ± 5.21 AU, P <0.001) were observed in comparison with pre-treatment, whereas GLUT4 was significantly increased (62.25 ± 11.77 ± 124.25 ± 21.01 AU, P< 0.001) only in BPD patients. Increased glucose uptake (M) was accompanied by a significant decrease of TNF-α mRNA (76.67 ± 12.59 14.01 ± 5.21 AU, P < 0.01) and an increase of GLUT4. The amounts of TNF-α mRNAs in skeletal muscle correlated inversely with GLUT4 mRNAs and directly with intramyocytic triglycerides levels, in a step-down regression analysis (r² = 0.95) TNFα mRNA (P=0.0014), muscular TG levels (P=0.018), and GLUT4 mRNA (P=0.028) resulted to be the most powerful independent variables for predicting M values. CONCLUSION/INTERPRETATION: These findings suggest that insulin resistance in morbidly obese patients is positively associated to the intramyocytic triglycerides content and to TNF-α gene expression and inversely correlated to GLUT4 expression. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index