Anti-inflammatory effects of excessive weight loss: Potent suppression of adipose interleukin 6 and tumour necrosis factor a expression
ABSTRACT 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.
- SourceAvailable from: Lora E Burke
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- "Adipose tissue is an active endocrine organ that produces and secretes pro-inflammatory cytokines (e.g., IL-6 and TNF-α) and anti-inflammatory cytokines (e.g., adiponectin and IL-10). There is evidence that IL-6 and TNF-α are elevated in obese individuals and decrease with weight loss  . In contrast, adiponectin and IL-10 are diminished in obese individuals and tend to increase with weight loss  . "
ABSTRACT: OBJECTIVE: To describe patterns of weight loss and regain and their effect on the pro-inflammatory cytokines IL-6 and TNF-α, and anti-inflammatory cytokines adiponectin and IL-10 during a 24-month weight loss trial. MATERIALS/METHODS: Participants were obese adults (N=66) who lost and regained ≥10lb during a 24-month clinical trial of behavioral weight loss treatment. Measurements of cytokines and weight were conducted at baseline, 6, 12, 18, and 24months. Linear mixed modeling was used to determine percent change in weight and cytokines from baseline. RESULTS: The sample was predominantly female (80.3%) and White (86.4%), with a mean age of 48.4±7.3years and mean BMI of 34.5±4.4kg/m(2). At baseline, men had higher waist circumference, body weight, and energy intake, and lower percent body fat and adiponectin. The largest decrease in weight was observed at 6months with a mean 11% decrease (p<.0001).A significant gender-by-weight change interaction on percent change in adiponectin was observed [b(se)=0.9 (0.2), p=.0003], with men having a larger increase in adiponectin with weight loss compared to women. There was a significant effect of weight gain over time with increases in IL-6 [b(se)=0.9 (0.3), p=.001]. CONCLUSIONS: Overall, weight loss was significantly associated with improvements in adiponectin and IL-6. Those improvements remained at 24months, following weight regain. The association between weight change and adiponectin was different between genders. Implementing strategies that support sustained weight loss can help prevent a state of chronic systemic inflammation and its associated adverse effects.Metabolism: clinical and experimental 05/2013; 62(9). DOI:10.1016/j.metabol.2013.04.004
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- "The adipose tissue is in obesity characterized by an increased production and secretion of inflammatory molecules like TNF-α and IL-6, which may have local and systemic effects. The amounts of TNF-α and IL-6 are positively correlated with body fat and decrease in obese patients after weight loss (Moschen et al 2010; Tilg & Kaser 2011; Moschen et al 2011). "
ABSTRACT: From a physiological perspective the sleep-wake cycle can be envisioned as a sequence of three physiological states (wakefulness, non-rapid eye movement, NREM, sleep and REM sleep) which are defined by a particular neuroendocrine-immune profile regulating the metabolic balance, body weight and inflammatory responses. Sleep deprivation and circadian disruption in contemporary "24/7 Society" lead to the predominance of pro-orexic and proinflammatory mechanisms that contribute to a pandemic metabolic syndrome (MS) including obesity, diabetes and atherosclerotic disease. Thus, a successful management of MS may require a drug that besides antagonizing the trigger factors of MS could also correct a disturbed sleep-wake rhythm. This review deals with the analysis of the therapeutic validity of melatonin in MS. Melatonin is an effective chronobiotic agent changing the phase and amplitude of the sleep/wake rhythm and having cytoprotective and immunomodulatory properties useful to prevent a number of MS sequels. Several studies support that melatonin can prevent hyperadiposity in animal models of obesity. Melatonin at a low dose (2-5 mg/day) has been used for improving sleep in patients with insomnia and circadian rhythm sleep disorders. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, TK 301). In clinical trials these analogs were employed in doses considerably higher than those usually employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin doses in the range of 50-100 mg/day are needed to assess its therapeutic value in MS.Neuro endocrinology letters 09/2011; 32(5):588-606.
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ABSTRACT: Whereas in most cases a fatty liver remains free of inflammation, 10%-20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple steatosis may be the consequence of a failure of antilipotoxic protection. In both situations, many parallel hits derived from the gut and/or the adipose tissue may promote liver inflammation. Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH.Hepatology 11/2010; 52(5):1836-46. DOI:10.1002/hep.24001