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

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.

AMP-activated protein kinase inhibits IL-6-stimulated inflammatory response in human liver cells by suppressing phosphorylation of signal transducer and activator of transcription 3 (STAT3)

“…This is primarily due to the strong correlation identified between increased levels of proinflammatory cytokines IL-6, TNF-α and IL-1β and insulin resistance [39,40]. Of these proinflammatory cytokines, circulating IL-6 levels have the strongest correlation with insulin resistance [39,41].…”

“…This is primarily due to the strong correlation identified between increased levels of proinflammatory cytokines IL-6, TNF-α and IL-1β and insulin resistance [39,40]. Of these proinflammatory cytokines, circulating IL-6 levels have the strongest correlation with insulin resistance [39,41]. IL-6 is highly produced by the adipose tissue and IL-6 levels are increased twofold to threefold in patients with obesity, insulin resistance and type 2 diabetes [42,43].…”

Dietary determinants of subclinical inflammation, dyslipidemia and components of the metabolic syndrome in overweight children: a review

“…60 It appears that TNF-a acts primarily through its transmembrane form in an autocrine/paracrine manner in adipocytes. 47,61,62 Thus, although TNF-a expression is increased in adipose tissue, circulating TNF-a in obese animals and humans is often not detectable or only mildly elevated. 62 Although dietary studies in obese children have focused mainly on the metabolic syndrome and dyslipidemia, 63,64 diet may also modulate the association between adiposity and subclinical inflammation.…”

Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state

“…1 Several molecules produced by adipose tissue, known as adipocytokines, circulate in increased concentration in several metabolic conditions. [2][3][4][5][6] Adiponectin (ApN), which is also exclusively produced by adipocytes, [7][8][9] is associated with improved insulin sensitivity through its stimulatory effect on fatty acid oxidation 10,11 and inhibitory action on hepatic glucose production. 12,13 Plasma ApN levels have been found to be significantly reduced in subjects with obesity, insulin resistance or DM2; [14][15][16][17] the mechanisms of this reduction are incompletely understood.…”