Although mast cell functions classically relate to allergic responses1–3, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm, and cancer4–8. This study presents evidence that mast cells contribute importantly to diet-induced obesity and diabetes. White adipose tissues (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Genetically determined mast cell deficiency and pharmacological stabilization of mast cells in mice reduce body weight gain and levels of inflammatory cytokines, chemokines, and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer of cytokine-deficient mast cells established that these cells contribute to mice adipose tissue cysteine protease cathepsin expression, apoptosis, and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance by production of IL6 and IFN-γ. Mast cell stabilizing agents in clinical use reduced obesity and diabetes in mice, suggesting the potential of developing novel therapies for these common human metabolic disorders.

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1.1. Types of Carbohydrates and Their Importance in the Chemical, Food, and Pharmaceutical Industries Carbohydrates used as large-scale feedstock in industry include starch, cellulose, sucrose, glucose, and fructose (Scheme 1); they provide a number of advantages for widespread application. Other important saccharides with promising properties for smallscale processes include chitin, chitosan, and uronic acidcontaining glycans. In this section, chemical, food, and pharmaceutical applications of these saccharides are reviewed.These carbohydrates are primarily obtained from renewable feedstocks made through photosynthetic pathways, that is, carbon fixation removing greenhouse gas from the environment. Furthermore, they do not contribute to fossil fuel consumption, therefore being greener than other raw materials. Cellulose and starch are among the most abundant polysaccharides in nature. The biological functions of cellulose and starch are very different, with starch acting as a reservoir of glucose storage for energy 8 and cellulose acting as a structural component in the cell. 9 The starch polymer has a backbone chain of α-D-(1→4)glucopyranose (amylose) with branches linked by α-D-(1→6)glucopyranose (amylopectin) that can be conveniently obtained from many important crops such as wheat, rice, maize, tapioca, potato, and sweet potato. 10 Starch is an economically important carbohydrate because of its partial solubility in water, digestibility by animals, and ability to be converted into other higher-value compounds (i.e., ethanol or Kojic acid) through fermentation. 11 Oxidation, esterification, hydroxyalkylation, hydrolysis, and cross-linking are the most common modifications for preparation of starch derivatives. 12 As a consequence, these derivatives have important applications in food, chemical, and energy industries, such as the preparation of plasticized films and composites, thickeners, and stabilizers for food preparation, and as a source of dextrins and glucose, prepared through enzymatic hydrolysis, for biofuel production. 13 Cellulose is a linear polymer composed entirely of β-D-(1→4)glucopyranose. It is the most abundant biopolymer on earth and the most environmentally friendly and sustainable raw material. It has been widely used as the primary source of paper and other applications including textiles, hydrogels for medical uses, films and thickeners, and bioethanol production. 9a,14 Chemical modifications of cellulose include oxidation, hydrolysis, alkylation, and composite synthesis with addition of other polymers. 15 Sucrose (β-D-fructofuranosyl-α-D-glucopyranoside) is a disaccharide widely found in plants and has been used as a sweetener for centuries. 16 Sucrose contains fructofuranose and glucopyranose that can be released by hydrolysis of its glycosidic bond. The enzymatic hydrolysis of sucrose produces a mixture of the two sugars, known as inverted sugars. Many research groups have put their efforts into optimizing new methods to obtain them. 17 These sugars are widely used in the foo...

The serine proteases of the intrinsic blood coagulation cascade are slowly neutralized by antithrombin (AT) 1 (reviewed in Ref. 1). This inhibition is secondary to the generation of 1:1 enzyme⅐AT complexes whose formation is dramatically enhanced by the mast cell product, heparin (2). Damus et al. (3) hypothesized that endothelial cell surface heparan sulfate proteoglycans (HSPGs) function in a similar fashion to accelerate coagulation enzyme inactivation by AT and therefore are responsible for the nonthrombogenic properties of blood vessels. We initially demonstrated that perfusion of the hind limbs of normal rodents and rodents deficient in mast cells with purified thrombin and AT leads to a greatly elevated rate of thrombin⅐AT complex formation and that the enzyme heparitinase as well as the natural heparin antagonist platelet factor 4 suppress the above acceleration (4, 5). We subsequently showed that cultured cloned bovine macrovascular and rodent microvascular endothelial cells synthesize both anticoagulant HSPG (HSPG act ) and nonanticoagulant HSPG (HSPG inact ) (6 -8). HSPG act bear glycosaminoglycan (GAG) chains that bind tightly to AT and accelerate thrombin⅐AT complex generation (6 -8).The biosynthesis of HSPG act requires generation of a core protein; assembly of a linkage region of four neutral sugars on specific serine attachment sites of the core protein; elongation of a GAG backbone composed of alternating N-acetylglu-