Matrix-assisted laser desorption/ionization (MALDI) is one of the most successful “soft” ionization methods in the field of mass spectrometry and enables the analysis of a broad range of molecules, including lipids. Although the details of the ionization process are still unknown, the importance of the matrix is commonly accepted. Both, the development of and the search for useful matrices was, and still is, an empirical process, since properties like vacuum stability, high absorption at the laser wavelength, etc. have to be fulfilled by a compound to become a useful matrix. This review provides a survey of successfully used MALDI matrices for the lipid analyses of complex biological samples. The advantages and drawbacks of the established organic matrix molecules (cinnamic or benzoic acid derivatives), liquid crystalline matrices, and mixtures of common matrices will be discussed. Furthermore, we will deal with nanocrystalline matrices, which are most suitable to analyze small molecules, such as free fatty acids. It will be shown that the analysis of mixtures and the quantitative analysis of small molecules can be easily performed if the matrix is carefully selected. Finally, some basic principles of how useful matrix compounds can be “designed” de novo will be introduced.

In obesity, hypertrophic adipocytes secrete high amounts of adipocytokines, resulting in low-grade inflammation amplified by infiltrating proinflammatory macrophages, oxidative stress, hypoxia, and lipolysis. These chronic proinflammatory conditions support the development of type II diabetes and cardiovascular diseases, but the mechanisms of obesity-related exacerbation of inflammatory skin disorders like psoriasis are unclear. In this study, we uncovered dietary saturated fatty acids (SFAs) as major risk factors for the amplification of skin inflammation, independent of obesity-related parameters such as fat mass extension, adipocytokine levels, and glucose homeostasis. Correlation analyses in a cohort of psoriasis vulgaris patients showed that free fatty acid serum level was the only obesity-associated parameter affecting disease severity. Studies in mice with high-fat diet-induced obesity with psoriasiform inflammation confirmed this critical role of free fatty acids. An increase of free fatty acids in healthy, lean mice alone was sufficient to induce an exacerbation of psoriasiform inflammation. In particular, saturated fatty acids sensitize myeloid cells to an increased inflammatory response in answer to proinflammatory stimuli, which in turn augments the activation of keratinocytes. Consequently, reduction of nutritional saturated fatty acids alone diminished the psoriatic phenotype in obese mice. Thus, our findings may open new perspectives for adjuvant dietary measures accompanying anti-inflammatory psoriasis therapies in lean and obese patients.

Obesity is associated with body fat gain and impaired glucose metabolism. Here, we identified both body fat gain in obesity and impaired glucose metabolism as two independent risk factors for increased serum levels of free fatty acids (FFAs). Since obesity is associated with increased and/or delayed resolution of inflammation observed in various chronic inflammatory diseases such as psoriasis, we investigated the impact of FFAs on human monocyte-derived and mouse bone marrow-derived dendritic cell (DCs) functions relevant for the pathogenesis of chronic inflammation. FFAs such as palmitic acid (PA) and oleic acid (OA) did not affect the pro-inflammatory immune response of DCs. In contrast, PA and OA sensitize DCs resulting in augmented secretion of TH1/TH17-instructive cytokines upon pro-inflammatory stimulation. Interestingly, obesity in mice worsened a TH1/TH17-driven psoriasis-like skin inflammation. Strong correlation of the amount of total FFA, PA, and OA in serum with the severity of skin inflammation points to a critical role of FFA in obesity-mediated exacerbation of skin inflammation. Our data suggest that increased levels of FFAs might be a predisposing factor promoting a TH1/TH17-mediated inflammation such as psoriasis in response to an inflammatory danger signal.Keywords: Dendritic cells r Diet r Free fatty acids r Inflammation r Metabolism r TH1 r TH17 Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionHuman and mouse studies demonstrate that immune responses are dysregulated in obesity. In particular, obesity in mice is associated with increased inflammation and/or its delayed resolution Correspondence: Dr. Anja Saalbach e-mail: Anja. Saalbach@medizin.uni-leipzig.de in models of acute pancreatitis, arthritis, and neutrophil-mediated peritonitis [1][2][3][4]. Kanemaru et al. described a worsening of psoriasis from dermatitis in mice by upregulating IL-17A, IL-22, and Reg3c in skin [5]. Likewise human psoriasis, a chronic TH1/TH17-driven inflammatory skin disease, shows a significant positive * These authors contributed equally to this work. Eur. J. Immunol. 2016Immunol. . 46: 2043Immunol. -2053 correlation between body mass index (BMI) and the onset and severity of the disease as well as a weaker response to treatment [6,7]. Obesity is associated with low-grade chronic inflammation reflected by increased levels of acute-phase proteins and pro-inflammatory mediators as well as by a pro-inflammatory state of circulating mononuclear cells in obese compared to lean subjects [3,8]. Enlarged adipocytes change their secretion pattern and release more pro-inflammatory mediators such as TNF-α and MCP-1, while the release of anti-inflammatory mediators such as adiponectin is reduced [9][10][11]. Thus, white adipose tissue could link metabolism and inflammation [12]. Moreover, in obesity, visceral adipose tissues as well as subcutaneous fat depots enlarge and adipocyte production of free fatty acids (FFAs), mainly palmitic acid (PA)...

Background G protein-coupled receptors (GPCR) are well-characterized regulators of a plethora of physiological functions among them the modulation of adipogenesis and adipocyte function. The class of Adhesion GPCR (aGPCR) and their role in adipose tissue, however, is poorly studied. With respect to the demand for novel targets in obesity treatment, we present a comprehensive study on the expression and function of this enigmatic GPCR class during adipogenesis and in mature adipocytes. Methods The expression of all aGPCR representatives was determined by reanalyzing RNA-Seq data and by performing qPCR in different mouse and human adipose tissues under low-and high-fat conditions. The impact of aGPCR expression on adipocyte differentiation and lipid accumulation was studied by siRNA-mediated knockdown of all expressed members of this receptor class. The biological characteristics and function of mature adipocytes lacking selected aGPCR were analyzed by mass spectrometry and biochemical methods (lipolysis, glucose uptake, adiponectin secretion). Results More than ten aGPCR are significantly expressed in visceral and subcutaneous adipose tissues and several aGPCR are differentially regulated under high-caloric conditions in human and mouse. Receptor knockdown of six receptors resulted in an impaired adipogenesis indicating their expression is essential for proper adipogenesis. The altered lipid composition was studied in more detail for two representatives, ADGRG2/GPR64 and ADGRG6/GPR126. While GPR126 is mainly involved in adipocyte differentiation, GPR64 has an additional role in mature adipocytes by regulating metabolic processes. Conclusions Adhesion GPCR are significantly involved in qualitative and quantitative adipocyte lipid accumulation and can control lipolysis. Factors driving adipocyte formation and function are governed by signaling pathways induced by aGPCR yielding these receptors potential targets for treating obesity.

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