Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha 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.
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ABSTRACT: Whole-genome genotyping and gene expression analyses in blood of 22 BMS and 23 AMS offspring from 19 mothers were conducted using Illumina HumanOmni-5-Quad and HumanHT-12 v4 Expression BeadChips, respectively. Using PLINK we analyzed interactions between offspring gene variations and maternal surgical status on offspring gene expression levels. Altered biological functions and pathways were identified and visualized using DAVID and Ingenuity Pathway Analysis. Significant interactions (p ≤ 1.22x10-12) were found for 525 among the 16,060 expressed transcripts: 1.9% of tested SNPs were involved. Gene function and pathway analysis demonstrated enrichment of transcription and of cellular metabolism functions and overrepresentation of cellular stress and signaling, immune response, inflammation, growth, proliferation and development pathways. We suggest that impaired maternal gestational metabolic fitness interacts with offspring gene variations modulating gene expression levels, providing potential mechanisms explaining improved cardiometabolic risk profiles of AMS offspring related to ameliorated maternal lipid and carbohydrate metabolism.PLoS ONE 01/2015; 10(1):e0117011. DOI:10.1371/journal.pone.0117011 · 3.53 Impact Factor
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ABSTRACT: Author contributions: Baptista LS and Borojevic R substantially contributed to the concept of the review and finalized the text; Baptista LS and Silva KR contributed to the text and designed the images. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: Abstract The discovery that adipose tissue represents an interesting source of multipotent stem cells has led to many studies exploring the clinical potential of these cells in cell-based therapies. Recent advances in understanding the secretory capacity of adipose tissue and the role of adipokines in the development of obesity and associated disorders have added a new dimension to the study of adipose tissue biology in normal and diseased states. Subcutaneous adipose tissue forms the interface between the clinical application of regenerative medicine and the establishment of the pathological condition of obesity. These two facets of adipose tissue should be understood as potentially related phenomena. Because of the functional characteristics of adipose stem cells, these cells represent a fundamental tool for understanding how these two facets are interconnected and could be important for therapeutic applications. In fact, adipose tissue stem cells have multiple functions in obesity related to adipogenic, angiogenic and secretory capacities. In addition, we have also previously described a predominance of larger blood vessels and an adipogenic memory in the subcutaneous adipose tissue after massive weight loss subsequent to bariatric surgery (ex-obese patients). Understanding the reversibility of the behavior of adipose stem cells in obeses and in weight loss is relevant to both physiological studies and the potential use of these cells in regenerative medicine. Core tip: In this mini-review, we summarize recent aspects regarding obese subcutaneous adipose tissue with a focus in adipogenic and secretory capacities of adipose stem cells. In particular, we discuss how the occurrence of obesity and weight loss could alter the properties of stem cells and the consequences of using adipose-derived stem cells in regenerative medicine. MINIREVIEWS Submit a Manuscript: Our previous results reveal that, after massive weight loss subsequent to bariatric surgery, stem cells retain an adipogenic memory besides a predominance of larger blood vessels in subcutaneous adipose tissue. Inflammatory subcutaneous adipose tissue microenvironment found in obese patients and even the massive weight loss could alter adipose tissue-derived stem cells phenotype to a non-healthy state. Baptista LS, Silva KR, Borojevic R. Obesity and weight loss could alter the properties of adipose stem cells? World J Stem Cells 2015; 7(1): 165-173 Available from:
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ABSTRACT: The approaches to alleviate low-grade systemic inflammation during postprandial period are still controversial at present. The aims of this article were to review the possible negative effects of postprandial inflammation and to provide potential way to prevent the risks to health during postprandial period through understanding the possible mechanism. Postprandial inflammation may lead to chronic low-grade systemic inflammation. Previous evidence showed that consumption of saturated fats, the elevation of circulating free fatty acids and high levels of blood glucose may lead to increased postprandial inflammation via activated NF-κB pathway, whereas, dietary with low GI, low saturated fats, and fiber-rich appeared to attenuate the postprandial inflammatory responses via down-regulating the NF-κB pathway. Furthermore, it has been suggested that weight loss may successfully lead to a significant reduction in postprandial inflammatory responses. Many studies indicated that exercise served as anti-inflammatory, however no sufficient and convincing evidence proves that exercise alleviated the subsequent postprandial inflammatory responses to date. Therefore, more studies are warranted to investigate the possible mechanisms of how different exercises and diet/meal/nutrients affect low-grade systemic inflammation.Current Topics in Nutraceutical Research 09/2013; 11(4):129-136. · 0.19 Impact Factor