Regulation of the nitric oxide system in human adipose tissue

Engeli, Stefan; Janke, Jürgen; Gorzelniak, Kerstin; Böhnke, Jana; Ghose, Nila; Lindschau, Carsten; Luft, Friedrich C.; Sharma, Arya M.

doi:10.1194/jlr.m300322-jlr200

Cited by 108 publications

(107 citation statements)

References 40 publications

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“…Nitric Oxide Signaling-Nitric oxide is involved in adipose tissue biology by influencing adipogenesis, insulin-stimulated glucose uptake, and lipolysis (111). We observed the presence of several enzymes responsible for nitric oxide formation (e.g.…”

Section: Tgf-␤/smadmentioning

confidence: 77%

Identification of Extracellular and Intracellular Signaling Components of the Mammary Adipose Tissue and Its Interstitial Fluid in High Risk Breast Cancer Patients

Celis

Moreira

Cabezón

et al. 2005

Molecular & Cellular Proteomics

208

164

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It has become clear that growth and progression of breast tumor cells not only depend on their malignant potential but also on factors present in the tumor microenvironment. Of the cell types that constitute the mammary stroma, the adipocytes are perhaps the least well studied despite the fact that they represent one of the most prominent cell types surrounding the breast tumor cells. There is compelling evidence demonstrating a role for the mammary fat pad in mammary gland development, and some studies have revealed the ability of fat tissue to augment the growth and ability to metastasize of mammary carcinoma cells. Very little is known, however, about which factors adipocytes produce that may orchestrate these actions and how this may come about. In an effort to shed some light on these questions, we present here a detailed proteomic analysis, using two-dimensional gel-based technology, mass spectrometry, immunoblotting, and antibody arrays, of adipose cells and interstitial fluid of fresh fat tissue samples collected from sites topologically distant from the tumors of high risk breast cancer patients that underwent mastectomy and that were not treated prior to surgery. A total of 359 unique proteins were identified, including numerous signaling molecules, hormones, cytokines, and growth factors, involved in a variety of biological processes such as signal transduction and cell communication; energy metabolism; protein metabolism; cell growth and/or maintenance; immune response; transport; regulation of nucleobase, nucleoside, and nucleic acid metabolism; and apoptosis. Apart from providing a comprehensive overview of the mammary fat proteome and its interstitial fluid, the results offer some insight as to the role of adipocytes in the breast tumor microenvironment and provide a first glance of their molecular cellular circuitry. In addition, the results open new possibilities to the study of obesity, which has a strong association with type 2 diabetes, hypertension, and coronary heart disease. Molecular & Cellular Proteomics 4: 492-522, 2005.During the last years there have been numerous reports indicating that growth and progression of breast as well as other tumor cells depend not only on their malignant potential but also on stromal factors present in the tumor microenvironment, the insoluble extracellular matrix as well as cell-cell interactions (Refs.

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Section: Tgf-␤/smadmentioning

confidence: 77%

Identification of Extracellular and Intracellular Signaling Components of the Mammary Adipose Tissue and Its Interstitial Fluid in High Risk Breast Cancer Patients

Celis

Moreira

Cabezón

et al. 2005

Molecular & Cellular Proteomics

208

164

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“…Changes in PKG are also associated with disorders such as obesity and diabetes. For example, high expression of cGK1 has been associated with obesity, and a reduction of PKG has been associated with diabetes and high glucose concentrations (Wang et al, 2002;Wang et al, 2003;Wang et al, 2004;Engeli et al, 2004;Su et al, 2003;Zanetti et al, 2005;Chang et al, 2004). Although a polymorphism in cGKI has not yet been found between obese and healthy mass populations (Zakharkin et al, 2005), the evidence from D. melanogaster larvae suggests that cGKI may help sustain a healthy mass by maintaining a balance between energy input and output.…”

Section: Discussionmentioning

confidence: 99%

Natural variation in food acquisition mediatedviaaDrosophilacGMP-dependent protein kinase

Kaun

Riedl

Chakaborty-Chatterjee

et al. 2007

Journal of Experimental Biology

115

138

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SUMMARY In natural environments where food abundance and quality can change drastically over time, animals must continuously alter their food acquisition strategies. Although genetic variation contributes to this plasticity, the specific genes involved and their interactions with the environment are poorly understood. Here we report that natural variation in the Drosophilagene, foraging (for), which encodes a cGMP-dependent protein kinase (PKG), affects larval food acquisition in an environmentally dependent fashion. When food is plentiful, the wild-type rover(forR) allele confers lower food intake and higher glucose absorption than both the wild-type sitter (fors) allele and the mutant fors2 allele. When food is scarce, forR, fors and fors2 larvae increase food intake to a common maximal level, but forRlarvae retain their increased absorption efficiency. Changes in forexpression can induce corrective behavioral modifications in response to food deprivation. When reared in environments with low food levels, forR larvae have higher survivorship and faster development than fors and fors2larvae. Together, these results show that natural variation in forhas far reaching implications affecting a suite of phenotypes involved in the regulation of food acquisition.

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“…More recently, iNOS disruption was also found to protect against the adverse effects of high-fat feeding on vascular insulin resistance (23) and to reduce insulin resistance in genetically obese ob/ob mice (24,25). Furthermore, iNOS is induced in skeletal muscle and adipose tissues of type 2 diabetic subjects (26,27) where its expression correlates with the occurrence of insulin resistance (27) and obesity (26).…”

mentioning

confidence: 99%

Obese Mice Lacking Inducible Nitric Oxide Synthase Are Sensitized to the Metabolic Actions of Peroxisome Proliferator–Activated Receptor-γ Agonism

et al. 2008

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OBJECTIVE-Synthetic ligands for peroxisome proliferatoractivated receptor-␥ (PPAR-␥) improve insulin sensitivity in obesity, but it is still unclear whether inflammatory signals modulate their metabolic actions. In this study, we tested whether targeted disruption of inducible nitric oxide (NO) synthase (iNOS), a key inflammatory mediator in obesity, modulates the metabolic effects of rosiglitazone in obese mice. RESEARCH DESIGN AND METHODS-iNOSϪ/Ϫ and iNOS ϩ/ϩ were subjected to a high-fat diet or standard diet for 18 weeks and were then treated with rosiglitazone for 2 weeks. Whole-body insulin sensitivity and glucose tolerance were determined and metabolic tissues harvested to assess activation of insulin and AMP-activated protein kinase (AMPK) signaling pathways and the levels of inflammatory mediators.RESULTS-Rosiglitazone was found to similarly improve whole-body insulin sensitivity and insulin signaling to Akt/PKB in skeletal muscle of obese iNOS Ϫ/Ϫ and obese iNOS ϩ/ϩ mice. However, rosiglitazone further improved glucose tolerance and liver insulin signaling only in obese mice lacking iNOS. This genotype-specific effect of rosiglitazone on glucose tolerance was linked to a markedly increased ability of the drug to raise plasma adiponectin levels. Accordingly, rosiglitazone increased AMPK activation in muscle and liver only in obese iNOS Ϫ/Ϫ mice. PPAR-␥ transcriptional activity was increased in adipose tissue of iNOS Ϫ/Ϫ mice. Conversely, treatment of 3T3-L1 adipocytes with a NO donor blunted PPAR-␥ activity. CONCLUSIONS-Our results identify the iNOS/NO pathway as a critical modulator of PPAR-␥ activation and circulating adiponectin levels and show that invalidation of this key inflammatory mediator improves the efficacy of PPAR-␥ agonism in an animal model of obesity and insulin resistance.

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Regulation of the nitric oxide system in human adipose tissue

Cited by 108 publications

References 40 publications

Identification of Extracellular and Intracellular Signaling Components of the Mammary Adipose Tissue and Its Interstitial Fluid in High Risk Breast Cancer Patients

Identification of Extracellular and Intracellular Signaling Components of the Mammary Adipose Tissue and Its Interstitial Fluid in High Risk Breast Cancer Patients

Natural variation in food acquisition mediatedviaaDrosophilacGMP-dependent protein kinase

Obese Mice Lacking Inducible Nitric Oxide Synthase Are Sensitized to the Metabolic Actions of Peroxisome Proliferator–Activated Receptor-γ Agonism

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