Evidence is emerging that dietary phytoestrogens play a beneficial role in obesity and diabetes. Nutritional intervention studies performed in animals and humans suggest that the ingestion of soy protein associated with isoflavones and flaxseed rich in lignans improves glucose control and insulin resistance. In animal models of obesity and diabetes, soy protein has been shown to reduce serum insulin and insulin resistance. In studies of human subjects with or without diabetes, soy protein also appears to moderate hyperglycemia and reduce body weight, hyperlipidemia, and hyperinsulinemia, supporting its beneficial effects on obesity and diabetes. However, most of these clinical trials were relatively short and involved a small number of patients. Furthermore, it is not clear whether the beneficial effects of soy protein and flaxseed are due to isoflavones (daidzein and genistein), lignans (matairesinol and secoisolariciresinol), or some other component. Isoflavones and lignans appear to act through various mechanisms that modulate pancreatic insulin secretion or through antioxidative actions. They may also act via estrogen receptor-mediated mechanisms. Some of these actions have been shown in vitro, but the relevance of these studies to in vivo disease is not known. The diversity of cellular actions of isoflavones and lignans supports their possible beneficial effects on various chronic diseases. Further investigations are needed to evaluate the long-term effects of phytoestrogens on obesity and diabetes mellitus and their associated possible complications.

Trimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is determined by a number of factors including diet, gut microbial flora and liver flavin monooxygenase activity. In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported. The atherogenic effect of TMAO is attributed to alterations in cholesterol and bile acid metabolism, activation of inflammatory pathways and promotion foam cell formation. TMAO levels increase with decreasing levels of kidney function and is associated with mortality in patients with chronic kidney disease. A number of therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that utilize TMAO as substrate and the development of target-specific molecules with varying level of success. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies examining the cellular signaling in physiology and pathological states in order to establish the role of TMAO in health and disease in humans.

Soy protein is an important component of soybeans and provides an abundant source of dietary protein. Among the dietary proteins, soy protein is considered a complete protein in that it contains ample amounts of all the essential amino acids plus several other macronutrients with a nutritional value roughly equivalent to that of animal protein of high biological value. Soy protein is unique among the plant-based proteins because it is associated with isoflavones, a group of compounds with a variety of biological properties that may potentially benefit human health. An increasing body of literature suggests that soy protein and its isoflavones may have a beneficial role in obesity. Several nutritional intervention studies in animals and humans indicate that consumption of soy protein reduces body weight and fat mass in addition to lowering plasma cholesterol and triglycerides. In animal models of obesity, soy protein ingestion limits or reduces body fat accumulation and improves insulin resistance, the hallmark of human obesity. In obese humans, dietary soy protein also reduces body weight and body fat mass in addition to reducing plasma lipids. Several potential mechanisms whereby soy protein may improve insulin resistance and lower body fat and blood lipids are discussed and include a wide spectrum of biochemical and molecular activities that favorably affect fatty acid metabolism and cholesterol homeostasis. The biologic actions of certain constituents of soy protein, particularly conglycinin, soyasaponins, phospholipids, and isoflavones, that relate to obesity are also discussed. In addition, the potential of soy protein in causing food allergy in humans is briefly discussed.

Hyperuricemia has long been established as the major etiologic factor in gout. In recent years, a large body of evidence has accumulated that suggests that hyperuricemia may play a role in the development and pathogenesis of a number of metabolic, hemodynamic, and systemic pathologic diseases, including metabolic syndrome, hypertension, stroke, and atherosclerosis. A number of epidemiologic studies have linked hyperuricemia with each of these disorders. In some studies, therapies that lower uric acid may prevent or improve certain components of the metabolic syndrome. There is an association between uric acid and the development of systemic lupus erythematosus; the connection between other rheumatic diseases such as rheumatoid arthritis and osteoarthritis is less clear. The mechanism for the role of uric acid in disorders other than gout is not well established but recent investigations point towards systemic inflammation induced by urate, as the major pathophysiological event common to systemic diseases, including atherosclerosis.

Osteoarthritis (OA) has become a major public health problem not only because of its increasing prevalence worldwide but also because of its frequent association with cardiovascular disease, the leading cause of death in industrialized countries. There is growing evidence that OA is not simply a disease related to aging or mechanical stress of joints but rather a "metabolic disorder" in which various interrelated lipid, metabolic, and humoral mediators contribute to the initiation and progression of the disease process. Indeed, OA has been linked not only to obesity but also to other cardiovascular risk factors, namely, diabetes, dyslipidemia, hypertension, and insulin resistance.

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Kidney disease, characterized by proteinuria and glomerular lesions, is a common complication of spontaneous diabetes mellitus in many animal species. It occurs in animals with hypoinsulinemia, hyperinsulinemia, or impaired glucose tolerance. The renal functional and structural abnormalities in spontaneously diabetic animals resemble human diabetic nephropathy in many respects. Mesangial expansion and glomerular basement membrane thickening, two structural hallmarks of diabetic glomerulopathy in humans, are the most frequently encountered lesions in animals. In addition, a nodular form of mesangial expansion that resembles but is not identical with human nodular glomerulosclerosis or the Kimmelstiel-Wilson lesion has been observed in some animal models. Other abnormalities, such as exudative hyaline lesions and arteriolar hyalinosis, have also been noted occasionally in other models. Although diabetic animals may develop kidney disease that resembles human diabetic nephropathy, no single animal model develops renal changes identical to those seen in humans. Nonetheless, animal models with spontaneous diabetic kidney disease may be useful for investigating the mechanisms of development of diabetic nephropathy and the effects of various treatment modalities on the progression of renal disease.

Current information suggests that osteoarthritis shares a similar biochemical and inflammatory profile to the metabolic syndrome. Mounting evidence exists to call attention to the fact that osteoarthritis deserves a seat at the Metabolic Syndrome 'table' of disorders.