Anti-inflammatory effects of excessive weight loss: Potent suppression of adipose interleukin 6 and tumour necrosis factor a expression

Christian Doppler Research Laboratory for Gut Inflammation and Department of Internal Medicine II, Medical University Innsbruck, 6020 Innsbruck, Austria.
Gut (Impact Factor: 14.66). 09/2010; 59(9):1259-64. DOI: 10.1136/gut.2010.214577
Source: PubMed


Severe obesity is a chronic inflammatory disease where various cytokines/adipocytokines play a key role. Pro-inflammatory cytokines such as interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNFalpha) are produced by human adipose tissue dependent on the degree of obesity. Mouse studies suggest a key role of adipose tissue-derived IL-6 in hepatic insulin resistance via modification of liver suppressor of cytokine signalling 3 (SOCS-3) expression.
We examined the effect of excessive weight loss on systemic levels, subcutaneous and visceral adipose tissue and liver expression of IL-6 and TNFalpha in 20 severely obese patients undergoing laparoscopic adjustable gastric banding (LAGB). Furthermore, we studied liver expression of SOCS3, an important regulator of insulin resistance, and fat tissue expression of the anti-inflammatory adipocytokine adiponectin and its receptors. Serum and tissue samples were collected before and 6 months after LAGB surgery.
IL-6/TNFalpha mRNA expression before weight loss were similar in subcutaneous and visceral adipose tissue and much higher compared to hepatic expression. Subcutaneous adipose tissue mRNA expression of both pro-inflammatory cytokines, but especially of IL-6 decreased dramatically after extensive weight loss whereas expression of adiponectin and its receptors increased. Weight loss also led to a significant reduction in liver IL-6 expression, whereas liver TNFalpha mRNA expression did not change. IL-6 and C-reactive protein serum levels decreased after weight loss whereas TNFalpha serum levels were below the detection limit before and after surgery. These effects were paralleled by reduced hepatic SOCS3 expression and improved insulin resistance 6 months after LAGB surgery.
Expression of IL-6 and TNFalpha mRNA is more pronounced in adipose compared to liver tissue in patients with severe obesity. Our results highlight excessive weight loss as a successful anti-inflammatory strategy.

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    • "Interestingly, bariatric surgery might also correct the pro-inflammatory state associated with obesity [46]. Indeed massive weight loss reduces adipose tissue pro-inflammatory mediators such as TNFa and IL6, which results in reduced expression of hepatic SOCS3, thus improving hepatic insulin resistance and inhibiting hepatic inflammation [47]. The only other RCT of dietary intervention and exercise in NAFLD was conducted in type 2 diabetics and did not have histological endpoints [48]. "
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    • "TNFα and IL6 are two important proinflammatory adipocytokines and the expression of both is hugely increased in the fat cells of obese human subjects and patients with IR.178,179 In patients with severe obesity, the mRNA expression of IL6 and TNFα is clearer in adipose compared to liver tissue.180 "
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    • "There are conflicting reports about the effect(s) of IL-6 on lipid and glucose metabolism and insulin sensitivity. The release of the adipokine IL-6 is related to BMI [127–129]. Fernandez-Real et al. demonstrated a positive association between IL-6 concentrations and the fasting insulin resistance index in 228 healthy volunteers [130]. Subcutaneous injections of recombinant human IL-6 also increase blood glucose and glucagon levels without changes in C-peptide levels, supporting the idea that IL-6 alters insulin sensitivity [131]. "
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