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Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance

Philip A. Kern, Subramanian Ranganathan, Chunling Li +2 more2001American Journal of Physiology-Endocrinology and MetabolismJournal Article
10.1152/ajpendo.2001.280.5.e745PubMed
CardiovascularEndocrine (ADH/ACTH/MSH)GastrointestinalHypothalamic-PituitaryImmune/InnateMusculoskeletalNeurologicalOcularRespiratory/Sinus
Bacterial EndotoxinsIndoor Mold (Stachybotrys, Aspergillus, etc.)MycotoxinsVolatile Organic Compounds (VOCs)Water-Damaged Buildings (WDB)

Abstract

Adipose tissue expresses tumor necrosis factor (TNF) and interleukin (IL)-6, which may cause obesity-related insulin resistance. We measured TNF and IL-6 expression in the adipose tissue of 50 lean and obese subjects without diabetes. Insulin sensitivity (S(I)) was determined by an intravenous glucose tolerance test with minimal-model analysis. When lean [body mass index (BMI) <25 kg/m(2)] and obese (BMI 30-40 kg/m(2)) subjects were compared, there was a 7.5-fold increase in TNF secretion (P < 0.05) from adipose tissue, and the TNF secretion was inversely related to S(I) (r = -0.42, P < 0.02). IL-6 was abundantly expressed by adipose tissue. In contrast to TNF, plasma (rather than adipose) IL-6 demonstrated the strongest relationship with obesity and insulin resistance. Plasma IL-6 was significantly higher in obese subjects and demonstrated a highly significant inverse relationship with S(I) (r = -0.71, P < 0.001). To separate the effects of BMI from S(I), subjects who were discordant for S(I) were matched for BMI, age, and gender. By use of this approach, subjects with low S(I) demonstrated a 3.0-fold increased level of TNF secretion from adipose tissue and a 2.3-fold higher plasma IL-6 level (P < 0.05) compared with matched subjects with a high S(I). Plasma IL-6 was significantly associated with plasma nonesterified fatty acid levels (r = 0.49, P < 0.002). Thus the local expression of TNF and plasma IL-6 are higher in subjects with obesity-related insulin resistance.

Key Biomarkers

Alpha Melanocyte Stimulating Hormone (MSH)Immunoglobulin E (IgE)LeptinMatrix Metalloproteinase 9 (MMP9)Vascular Endothelial Growth Factor (VEGF)Visual Contrast Sensitivity (VCS)

Symptom Clusters

Appetite swingsChronic painConfusionCoughDifficulty with concentrationExcessive thirstFatigueFrequent urinationHeadacheIce pick painJoint painLight sensitivityMemory lossMood swingsMuscle achesNight sweatsShortness of breathSinus congestionSleep disturbanceTingling in extremities

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  • References (1)

    • Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin ResistanceScience · 1993
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