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

International Journal of Obesity volume 26, pages 1165–1172 (2002)Cite this article

Abstract

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.

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Authors and Affiliations

  1. Istituto di Medicina Interna, Università Cattolica S Cuore, Rome, Italy

    G Mingrone, P Di Rocco, M Manco, E Capristo, G Gasbarrini & AV Greco

  2. Clinica Chirurgica and Centro di Fisiopatologia dello Shock CNR, Università Cattolica S Cuore, Rome, Italy

    G Rosa & M Castagneto

  3. Department of Medical and Surgical Sciences, the Endocrine-Metabolic Laboratory, University of Padua, Padua, Italy

    R Vettor

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  1. G Mingrone
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Correspondence to G Mingrone.

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Mingrone, G., Rosa, G., Di Rocco, P. et al. Skeletal muscle triglycerides lowering is associated with net improvement of insulin sensitivity, TNF-α reduction and GLUT4 expression enhancement. Int J Obes 26, 1165–1172 (2002). https://doi.org/10.1038/sj.ijo.0802053

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