Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche.

Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the "button mushroom" forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost and during mushroom formation. The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation are more highly expressed in compost. The striking expansion of heme-thiolate peroxidases and ß-etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics.

The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes.

CONTEXT: Obesity-associated inflammation is a contributory factor in the pathogenesis of type 2 diabetes mellitus (T2DM); the mechanisms underlying the progression to T2DM are unclear. The adipokine resistin has demonstrated proinflammatory properties in relation to obesity and T2DM. OBJECTIVES: The objectives of this study were to characterize resistin expression in human obesity and address the role of resistin in the innate immune pathway; to examine the influence of lipopolysaccharide, recombinant human resistin (rhResistin), insulin, and rosiglitazone in human adipocytes; and, finally, to analyze the effect of rhResistin on the expression of components of the nuclear factor-kappaB pathway and insulin signaling cascade. METHODS: Abdominal sc adipose tissue was obtained from patients undergoing elective liposuction surgery (n = 35; age, 36-49 yr; body mass index, 26.5 +/- 5.9 kg/m2). Isolated adipocytes were cultured with rhResistin (10-50 ng/ml). The level of cytokine secretion from isolated adipocytes was examined by ELISA. The effect of rhResistin on protein expression of components of the innate immune pathway was examined by Western blot. RESULTS: In vitro studies demonstrated that antigenic stimuli increase resistin secretion (P < 0.001) from isolated adipocytes. Proinflammatory cytokine levels were increased in response to rhResistin (P < 0.001); this was attenuated by rosiglitazone (P < 0.01). When examining components of the innate immune pathway, rhResistin stimulated Toll-like receptor-2 protein expression. Similarly, mediators of the insulin signaling pathway, phosphospecific c-Jun NH2-terminal kinase (JNK) 1 and JNK2, were up-regulated in response to rhResistin. CONCLUSION: Resistin may participate in more than one mechanism to influence proinflammatory cytokine release from human adipocytes, potentially via the integration of nuclear factor-kappaB and JNK signaling pathways.

Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease.

INTRODUCTION: Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood. METHODS: For these studies the expression of inflammatory markers was assessed in epicardial fat biopsies from coronary artery bypass grafting (CABG) patients using quantitative RT-PCR. Further, the effects of chronic medications, including statins, as well as peri-operative glucose, insulin and potassium infusion, on gene expression were also assessed. Circulating resistin, CRP, adiponectin and leptin levels were determined to assess inflammation. RESULTS: The expression of adiponectin, resistin and other adipocytokine mRNAs were comparable to that in omental fat. Epicardial CD45 expression was significantly higher than control depots (p < 0.01) indicating significant infiltration of macrophages. Statin treated patients showed significantly lower epicardial expression of IL-6 mRNA, in comparison with the control abdominal depots (p < 0.001). The serum profile of CABG patients showed significantly higher levels of both CRP (control: 1.28 +/- 1.57 microg/mL vs CABG: 9.11 +/- 15.7 microg/mL; p < 0.001) and resistin (control: 10.53 +/- 0.81 ng/mL vs CABG: 16.8 +/- 1.69 ng/mL; p < 0.01) and significantly lower levels of adiponectin (control: 29.1 +/- 14.8 microg/mL vs CABG: 11.9 +/- 6.0 microg/mL; p < 0.05) when compared to BMI matched controls. CONCLUSION: Epicardial and omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise in part from macrophage infiltration into the epicardial fat. This study highlights that chronic inflammation occurs locally as well as systemically potentially contributing further to the pathogenesis of coronary artery disease.