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

Int J Obes Relat Metab Disord. 2002 Sep;26(9):1165-72. doi: 10.1038/sj.ijo.0802053.


Aims/hypothesis: The aim of the present study was to investigate the relationship between intramyocytic triglycerides levels, muscle TNF-alpha and GLUT4 expression and insulin resistance.

Methods: Insulin sensitivity was studied in 14 severely obese women (BMI>40 kg/m(2)), 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-alpha 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-alpha 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-alpha mRNA (76.67+/-12.59-14.01+/-5.21 AU, P<0.01) and an increase of GLUT4. The amounts of TNF-alpha mRNAs in skeletal muscle correlated inversely with GLUT4 mRNAs and directly with intramyocytic triglycerides levels. In a step-down regression analysis (r(2)=0.95) TNFalpha 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-alpha gene expression and inversely correlated to GLUT4 expression.

MeSH terms

  • Adult
  • Biliopancreatic Diversion
  • Biopsy, Needle
  • Blood Glucose / metabolism
  • Body Composition / physiology
  • Diet, Reducing
  • Electrophoresis, Agar Gel
  • Female
  • Gene Expression / physiology*
  • Glucose Clamp Technique
  • Glucose Transporter Type 4
  • Humans
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance / physiology*
  • Monosaccharide Transport Proteins / metabolism*
  • Muscle Proteins*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / surgery
  • Obesity, Morbid / diet therapy
  • Obesity, Morbid / metabolism*
  • Obesity, Morbid / surgery
  • RNA, Messenger / metabolism
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*
  • Weight Loss / physiology


  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • RNA, Messenger
  • SLC2A4 protein, human
  • Triglycerides
  • Tumor Necrosis Factor-alpha