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Subcutaneous adipose tissue expression of tumour necrosis factor-alpha is not associated with whole body insulin resistance in obese nondiabetic or in type-2 diabetic subjects
Authors:Koistinen H A  Bastard J P  Dusserre E  Ebeling P  Zegari N  Andreelli F  Jardel C  Donner M  Meyer L  Moulin P  Hainque B  Riou J P  Laville M  Koivisto V A  Vidal H
Affiliation:Helsinki University Central Hospital, Finland; H?pital de la Salpétrière, Paris, France. heikki_koistinen@yahoo.com
Abstract:BACKGROUND: An association with subcutaneous adipose tissue TNFalpha expression and insulin resistance has been suggested in obesity/type-2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type-2 diabetic men. In the second part of the study we examined the relationship between adipose tissue TNFalpha mRNA levels and BMI in 81 nondiabetic subjects spanning a wide range of BMIs. METHODS: Subcutaneous adipose tissue TNFalpha mRNA levels and insulin sensitivity were determined with quantitative RT-competitive PCR and hyperinsulinaemic clamp, respectively. RESULTS: Subcutaneous adipose tissue TNFalpha mRNA levels were similar in 7 lean and 10 obese nondiabetic and 9 type-2 diabetic men (P = 0.68), and did not change in response to 240-min hyperinsulinaemia. TNFalpha mRNA levels and insulin sensitivity were not correlated. Unexpectedly, no correlation between TNFalpha mRNA and BMI was found. The relationship between adipose tissue TNFalpha mRNA and BMI was examined further in 31 male and 50 female nondiabetic subjects. The subcutaneous adipose tissue TNFalpha mRNA level correlated with BMI in all subjects (rS = 0.32, P < 0.01), and in a subgroup analysis in men (rS = 0.55, P < 0.01) but not in women (rS = - 0.08). The correlation in men was dependent on a fourfold higher TNFalpha mRNA level in 5 morbidly obese men while there was no difference in TNFalpha mRNA levels in lean or obese men. CONCLUSIONS: Subcutaneous adipose tissue TNFalpha expression does not correlate with insulin sensitivity in nondiabetic or type-2 diabetic men; is not regulated by acute hyperinsulinaemia; and is increased only in morbidly obese men.
Keywords:Cytokine    hyperinsulinaemic clamp    insulin resistance    obesity    tumour necrosis factor-α
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