The Decrease of Serum Levels of Human Neutrophil Alpha-Defensins Parallels with the Surgery-Induced Amelioration of NASH in Obesity

Manco, Melania; Fernández‐Real, José Manuel; Vecchio, Fabio Maria; Vellone, Valerio Gaetano; Moreno, José María Ruiz; Tondolo, Vincenzo; Bottazzo, G. F.; Nanni, Giuseppe; Mingrone, Geltrude

doi:10.1007/s11695-010-0129-8

Cited by 18 publications

(13 citation statements)

References 51 publications

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“…We found that the mRNA levels of two antimicrobial peptides, cathelicidin antimicrobial peptide ( CAMP ) and alpha defensin 1/3 ( DEFA1/DEFA3 ), were significantly decreased after bariatric surgery. In two prior studies, plasma levels of alpha defensins were found to be decreased by 55 to 60% in women after bariatric surgery, and their levels were correlated with changes in plasma triglyceride levels and pathology based measures of liver steatosis and inflammation [23], [24]. Thus, our finding of decreased DEFA1/DEFA3 mRNA levels after bariatric surgery agrees with prior findings from plasma protein level measurement assays.…”

Section: Discussionsupporting

confidence: 90%

Changes in Whole Blood Gene Expression in Obese Subjects with Type 2 Diabetes Following Bariatric Surgery: a Pilot Study

et al. 2011

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BackgroundA pilot study was performed in order to investigate the effects of bariatric surgery on whole blood gene expression profiles in obese subjects with type 2 diabetes.Methodology/Principal FindingsWhole blood from eleven obese subjects with type 2 diabetes was collected in PAXgene tubes prior to and 6–12 months after bariatric surgery. Total RNA was isolated, amplified, labeled and hybridized to Illumina gene expression microarrays. Clinical and expression data were analyzed using a paired t-test, and correlations between changes in clinical trait and transcript levels were calculated. Pathways were identified using Ingenuity Pathway Analysis and DAVID gene ontology software. Overall, bariatric surgery resulted in significant reduction of body mass index, fasting plasma glucose, fasting plasma insulin, and normalization of glycosylated hemoglobin levels. The expression levels of 204 transcripts, representing 200 unique genes, were significantly altered after bariatric surgery. Among the significantly regulated genes were GGT1, CAMP, DEFA1, LCN2, TP53, PDSS1, OLR1, CNTNAP5, DHCR24, HHAT and SARDH, which have been previously implicated in lipid metabolism, obesity and/or type 2 diabetes. Selected findings were replicated by quantitative real-time-PCR. The changes in expression of seven transcripts, WDR35, FLF45244, DHCR24, TIGD7, TOPBP1, TSHZ1, and FAM8A1 were strongly correlated with the changes in body weight, fasting plasma glucose and glycosylated hemoglobin content. The top pathways associated with gene expression changes after bariatric surgery was lipid metabolism, small molecule biochemistry and gene expression. Two antimicrobial peptides were among the transcripts with the largest changes in gene expression after bariatric surgery.Conclusions/SignificanceData from this pilot study suggest that whole blood expression levels of specific transcripts may be useful as biomarkers associated with susceptibility for type 2 diabetes and/or therapeutic response.

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Section: Discussionsupporting

confidence: 90%

Changes in Whole Blood Gene Expression in Obese Subjects with Type 2 Diabetes Following Bariatric Surgery: a Pilot Study

et al. 2011

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“…This association may be envisioned as an attempt to buffer metabolic endotoxemia with increased fat mass. However, increased metabolic endotoxemia possibly results in increased turnover of sCD14 because weight loss results in both decreased LPS (J.M.M.-N. and J.M.F.-R. unpublished results) and increased sCD14 levels (29). …”

Section: Discussionmentioning

confidence: 99%

CD14 Modulates Inflammation-Driven Insulin Resistance

et al. 2011

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OBJECTIVEThe study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance.RESEARCH DESIGN AND METHODSThe effects of recombinant human soluble CD14 (rh-sCD14) on insulin sensitivity (clamp procedure) and adipose tissue gene expression were evaluated in wild-type (WT) mice, high fat–fed mice, ob/ob mice, and CD14 knockout (KO) mice. We also studied WT mice grafted with bone marrow stem cells from WT donor mice and CD14 KO mice. Finally, CD14 was evaluated in human adipose tissue and during differentiation of human preadipocytes.RESULTSrh-sCD14 led to increased insulin action in WT mice, high-fat–fed mice, and ob/ob mice, but not in CD14 KO mice, in parallel to a marked change in the expression of 3,479 genes in adipose tissue. The changes in gene families related to lipid metabolism were most remarkable. WT mice grafted with bone marrow stem cells from WT donor mice became insulin resistant after a high-fat diet. Conversely, WT mice grafted with cells from CD14 KO mice resisted the occurrence of insulin resistance in parallel to decreased mesenteric adipose tissue inflammatory gene expression. Glucose intolerance did not worsen in CD14 KO mice grafted with bone marrow stem cells from high fat–fed WT mice when compared with recipient KO mice grafted with cells from CD14 KO donor mice. CD14 gene expression was increased in whole adipose tissue and adipocytes from obese humans and further increased after tumor necrosis factor-α.CONCLUSIONSCD14 modulates adipose tissue inflammatory activity and insulin resistance.

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“…sCD14 is involved in innate immunity and its expression is increased by the presence of LPS and fatty acids that resemble the lipid portion of LPS. 34 It was also noted that mothers of children who were normal weight at age 10 y had statistically significantly higher mean concentrations of adiponectin in maternal colostrum than mothers of overweight children. Adiponectin is a protein hormone secreted from adipose tissue 35 and the placenta 36 into the blood stream.…”

Section: Other Technologies Employed To Investigate Microbial Ecosystemsmentioning

confidence: 97%

The gut microbiota and its relationship to diet and obesity

et al. 2012

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The Decrease of Serum Levels of Human Neutrophil Alpha-Defensins Parallels with the Surgery-Induced Amelioration of NASH in Obesity

Abstract: Changes in levels of HNDs and sCD14 accompany those in hepatic necro-inflammation due to surgical-induced weight loss. Further studies are needed to verify any causative role of these peptides in non-alcoholic steatohepatitis.

Cited by 18 publications

References 51 publications

Changes in Whole Blood Gene Expression in Obese Subjects with Type 2 Diabetes Following Bariatric Surgery: a Pilot Study

Changes in Whole Blood Gene Expression in Obese Subjects with Type 2 Diabetes Following Bariatric Surgery: a Pilot Study

CD14 Modulates Inflammation-Driven Insulin Resistance

The gut microbiota and its relationship to diet and obesity

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