Role of dietary soy protein in obesity.

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.

Relationship between fatty acids and the endocrine and neuroendocrine system.

Significant interactions exist between fatty acids and the endocrine system. Dietary fatty acids alter both hormone and neuropeptide concentrations and also their receptors. In addition, hormones affect the metabolism of fatty acids and the fatty acid composition of tissue lipids. The principal hormones involved in lipid metabolism are insulin, glucagon, catecholamines, cortisol and growth hormone. The concentrations of these hormones are altered in chronic degenerative conditions such as diabetes and cardiovascular disease, which in turn leads to alterations in tissue lipids. Lipogenesis and lipolysis, which modulate fatty acid concentrations in plasma and tissues, are under hormonal control. Neuropeptides are also involved in lipid metabolism in brain and other tissues. Polyunsaturated fatty acids are also precursors for eicosanoids including prostaglandins, leucotrienes, and thromboxanes, which have hormone-like activities. Fatty acids in turn affect the endocrine system. Saturated and trans fatty acids decrease insulin concentration leading to insulin resistance. In contrast, polyunsaturated fatty acids increase plasma insulin concentration and decrease insulin resistance. In humans, omega3 polyunsaturated fatty acids alter the levels of opioid peptides in plasma. Free fatty acids have been reported to inhibit glucagon release. Fatty acids also affect receptors for hormones and neuropeptides.

Modulation of carbohydrate metabolism and peptide hormones by soybean isoflavones and probiotics in obesity and diabetes.

Soybean and its isoflavones have been shown to have beneficial effects on carbohydrate and lipid metabolism and on renal function. Probiotics may potentiate the beneficial effects of isoflavones by converting the inactive isoflavone glycoside to aglycones, which are biologically active, thereby producing a synergistic effect. We therefore studied the effects of soybean isoflavones in the presence and absence of probiotics on glucose and triglyceride metabolism and the peptide hormones involved in their metabolism. Lean and obese SHR/N-cp rats were fed AIN-93 diets containing 0.1% soybean isoflavone mixture, 0.1% probiotics mixture or both. Plasma was analyzed for glucose, triglycerides, parameters of renal function and peptide hormones -- insulin, leptin, glucagon and ACTH -- that are involved in glucose and lipid metabolism. Isoflavones given alone lowered plasma glucose in both phenotypes while triglyceride was decreased only in lean animals. Isoflavones also lowered aspartate amino transferase and alanine amino transferase in both phenotypes. Isoflavones had significant effect on plasma insulin, leptin and glucagon in lean rats but not in obese rats. Thus, our data show that in lean animals, isoflavones have hypoglycemic and hypolipidemic effect, and the effect is mediated by changes in peptide hormones. When lipid levels are very high as in obese rats, isoflavones fail to lower plasma triglyceride levels. Probiotics do not appear to enhance the effect of isoflavones.

Proinflammatory cytokines and the hypermetabolism of children with sickle cell disease.

Sickle cell anemia (HbSS) includes chronic inflammation, but the origin is unclear. We hypothesized that in stable HbSS patients the inflammation was associated with hypermetabolism. We compared selected hypermetabolic and key immunomodulator indicators in HbSS versus control children and examined associations between measures of hypermetabolism and inflammation. Twelve fasting asymptomatic HbSS children 6-12 years and 9 controls matched for age, gender and fat mass (FM) were studied. Proportional reticulocyte count (retic%) and resting energy expenditure (REE) represented hypermetabolism, and C-reactive protein (CRP) indicated inflammation. Proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), chemokine monocyte chemoattractant protein-1 (MCP-1), and energy balance cytokine leptin were measured. Methods were indirect calorimetry, enzyme-linked immunosorbent assay, and radioimmunoassay. Statistical analysis included simple correlation and regression analysis. REE (51 +/- 6 vs. 43 +/- 12 kcal/kg per fat-free mass (FFM), mean +/- SD), retic% (12 +/- 4 vs. 0.7 +/- 0.3%), CRP (5 +/- 3 vs. 0.3 +/- 0.4 mg/liter), and IL-6 (71 +/- 40 vs. 20 +/- 7 pg/ml) were significantly higher for HbSS than controls (P < 0.05). Conversely, leptin (0.1 +/- 0.1 vs. 2 +/- 1 microg/liter per kgFM) and MCP-1 (34 +/- 5 vs. 41 +/- 4 pg/ml) were significantly lower for the HbSS subjects (P < 0.01). TNF-alpha was not significantly different. There were no significant associations between REE or retic% and any cytokine measured. However, CRP was significantly associated with REE in HbSS (r = 0.8, P = 0.003) and an important predictor of REE/FFM. We provide new evidence for low circulating levels of inflammatory chemokine MCP-1 in stable HbSS children, confirm mostly low cytokine levels, inflammation, and hypermetabolism and demonstrate association of hypermetabolism with inflammation via CRP but not via cytokines.

Effects of soybean isoflavones, probiotics, and their interactions on lipid metabolism and endocrine system in an animal model of obesity and diabetes.

The effects of soybean isoflavones with or without probiotics on tissue fat deposition, plasma cholesterol, and steroid and thyroid hormones were studied in SHR/N-cp rats, an animal model of obesity, and were compared to lean phenotype. We tested the hypothesis that probiotics by promoting the conversion of isoflavone glycosides to their metabolically active aglycone form will have a synergistic effect on body fat, cholesterol metabolism, and the endocrine system. Obese and lean SHR/N-cp rats were fed AIN-93 diets containing 0.1% soy isoflavone mixture, 0.1% probiotic mixture, or both together. Different fat tissues were teased and weighed. Plasma was analyzed for cholesterol and steroid and thyroid hormones. In both phenotypes, isoflavones lowered fat deposition in several fat depots. Probiotics alone had no significant effect on fat depots. Isoflavones lowered total, LDL, and HDL cholesterol in lean rats, but in obese rats isoflavones lowered only total and LDL cholesterol. Isoflavones also lowered many of the steroid hormones involved in lipid metabolism but had no significant effect on thyroid hormones. Probiotics had no significant effect on cholesterol or hormones. Thus, our data show that soy isoflavones also lower plasma cholesterol and that this hypocholesterolemic effect appears to be due in part to the modulation of steroid hormones. Probiotics do not seem to enhance the effect of isoflavones.

Dietary flaxseed meal reduces proteinuria and ameliorates nephropathy in an animal model of type II diabetes mellitus.

BACKGROUND: Evidence is emerging that varying the type or source of dietary protein intake can have beneficial effects on chronic renal disease. Consumption of soybean and soy-based food products, as the source of plant protein, can retard the development and progression of chronic renal disease. We studied the obese spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat, a model of obesity and type II diabetes mellitus that consistently develops nephropathy resembling diabetic nephropathy. We specifically sought to determine whether changing the source of protein intake from animal protein, casein, to plant protein in the form of either soy protein concentrate or flaxseed protein in the diet has a different impact on renal function and nephropathy in this model. METHODS: Male obese SHR/N-cp rats were randomly assigned to one of three diets containing either 20% casein, 20% soy protein concentrate, or 20% flaxseed meal. Except for the protein source, all three diets were identical and contained similar amounts of protein, fat, carbohydrates, minerals, and vitamins. All animals were maintained on these diets for 6 months. At the end of the study, blood sampling and 24-hour urine collections were performed for renal functional measurements, and the kidneys were harvested and examined for histologic evaluation. RESULTS: All three groups had similar amounts of food intake and body weight gain and exhibited fasting hyperglycemia and hyperinsulinemia. Plasma glucose levels did not differ among the three groups, but plasma insulin concentration was significantly lower in rats fed flaxseed meal than those fed either casein or soy protein concentrate. Mean plasma creatinine, creatinine clearance, and urinary urea excretion also did not differ significantly between the three groups. By contrast, urinary protein excretion was significantly lower (P < 0.01) in rats fed flaxseed than in rats fed either casein or soy protein concentrate. Morphologic analysis of renal structural lesions showed that the percentage of abnormal glomeruli with mesangial expansion and the tubulointerstitial score (an index of severity of tubulointerstitial damage) were significantly reduced in rats fed flaxmeal compared to those fed casein or soy protein concentrate. CONCLUSION: We conclude that dietary protein substitution with flaxseed meal reduces proteinuria and glomerular and tubulointerstitial lesions in obese SHR/N-cp rats and that flaxseed meal is more effective than soy protein in reducing proteinuria and renal histologic abnormalities in this model. The reduction in proteinuria and renal injury was independent of the amount of protein intake and glycemic control. Which dietary component(s) present in flaxseed meal is (are) responsible for the renal protective effect remains to be determined.

Dietary flaxseed meal is more protective than soy protein concentrate against hypertriglyceridemia and steatosis of the liver in an animal model of obesity.

OBJECTIVE: Soy protein and flaxseed meal have been reported to have beneficial effects on many chronic diseases in humans and animals. The primary objective of the study was to evaluate the beneficial effects of soy protein and flaxseed meal on hypertriglyceridemia and liver steatosis associated with obesity and diabetes. We compared the effects of dietary soy protein and flaxseed meal with that of casein on plasma and liver lipids in a genetic model of obesity, type II diabetes and insulin resistance, namely the SHR/N-cp rat. METHODS: Lean and obese phenotypes of SHR/-cp rats were fed AIN 93 diets containing 20% of energy from casein (control), soy protein concentrate or flaxseed meal for six months. Plasma was analyzed for total cholesterol, LDL cholesterol, triglyceride and total protein. Liver was analyzed for steatosis by light microscopy after staining samples with Hematoxylin-Eosin and Oil-Red-O. RESULTS: In lean rats soy protein and flaxseed meal significantly decreased plasma total cholesterol (26.0% and 20.3% respectively) compared to casein. In obese rats flaxseed meal had significant cholesterol lowering effect compared to control rats (41%). Soy protein significantly lowered both plasma LDL-cholesterol and HDL-cholesterol in lean phenotypes while in obese phenotypes flaxseed meal significantly lowered LDL-cholesterol and HDL-cholesterol compared to casein-fed rats. Flaxseed meal also significantly lowered plasma triglyceride in both lean and obese rats compared to casein fed rats (33.7% and 37% respectively). There was significantly greater fat accumulation in livers of obese rats than lean rats (200%) regardless of dietary protein type. Flaxseed meal significantly lowered fat deposition in livers of both lean and obese rats compared to rats fed casein or soy protein. Dietary component(s) present in flaxseed meal or soy protein responsible for hypolipidemic effects is not clear. CONCLUSIONS: The marked hypotriglyceridemic and hypocholesterolemic effects of flaxseed meal may have important therapeutic implications in patients with hypertriglyceridemia and hypercholesterolemia and deserve further study in humans with these disorders. Flaxseed meal supplementation may provide a new therapeutic strategy to reduce hypertriglyceridemia and fatty liver.

Beneficial role of dietary phytoestrogens in obesity and diabetes.

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.

The effect of dietary menhaden, olive, and coconut oil fed with three levels of vitamin E on plasma and liver lipids and plasma fatty acid composition in rats.

The effect of dietary fats with varying degrees of unsaturation in the presence of different concentrations of vitamin E on tissue lipid levels was studied in rats. Rats were fed either menhaden oil, olive oil or coconut oil at 15% levels with either 0.1, 0.3 or 0.6 mg/g of vitamin E as alpha-tocopherol for four weeks. Rat serum and liver were analyzed for total cholesterol, HDL-cholesterol, triacylglycerol and phospholipids. In addition, fatty acid composition of serum lipids was also analyzed. Serum total cholesterol and triacylglycerol were significantly lower in rats fed menhaden oil than in those fed olive or coconut oil, while the HDL-cholesterol was significantly higher in serum of rats fed menhaden and olive oil than in those fed coconut oil. Levels of vitamin E in the diet had only a significant effect on serum cholesterol and liver phospholipids. The Pearson correlation coefficient showed a significant positive relationship between serum triacylglycerol and total cholesterol, and a negative correlation between triacylglycerol and HDL-cholesterol, and between total and HDL-cholesterol.In the liver, total cholesterol was significantly higher in rats fed coconut oil than in rats fed menhaden oil. Total liver phospholipids were lower in rats fed either coconut oil or olive oil compared to those fed menhaden oil, especially with higher levels of vitamin E intake. Higher levels of vitamin E in the diet appear to increase triacylglycerol and phospholipids in livers of rats fed menhaden oil. In the liver a significant negative correlation was observed between phospholipids and cholesterol. The type and degree of unsaturation (polyunsaturated fatty acids in menhaden oil, monounsaturated fatty acids in olive oil and saturated fatty acids in coconut oil) significantly affected plasma and tissue lipids.

Differential effects of dietary flaxseed protein and soy protein on plasma triglyceride and uric acid levels in animal models.

The effect of dietary soy protein and flaxseed meal on metabolic parameters was studied in two animal models, F344 rats with normal lipid levels and obese SHR/N-cp rats with elevated levels of cholesterol and triglyceride. The rats were fed AIN 93 diet differing only in the source of protein. The rats were fed either 20% casein, 20% soy protein or 20% flaxseed meal. Plasma was analyzed for cholesterol, triglyceride, uric acid, blood urea nitrogen (BUN), creatinine and total protein. In both strains of rats, flaxseed meal significantly decreased plasma cholesterol and triglyceride concentrations. The effect of soy protein on lipids was not as striking as that of flaxseed meal. Flaxseed meal also lowered uric acid in F344 rats and BUN in SHR/N-cp rats. Since cholesterol, triglyceride and uric acid are independent risk factors for cardiovascular disorders, our data show that both flaxseed meal and soy protein may have beneficial effects. Which chemical constituent(s) of flaxseed meal or soybean is (are) responsible for the beneficial effects need to be identified.

Fructose metabolizing enzymes in the rat liver and metabolic parameters: Interactions between dietary copper, type of carbohydrates, and gender.

This study was conducted to determine the effects of nutrient interactions between dietary carbohydrates and copper levels on fructose-metabolizing hepatic enzymes in male and female rats. Male and female rats were fed diets for 5 weeks that were either adequate or deficient in copper that contained either starch or fructose. Rats of both sexes fed fructose as compared with those fed starch showed higher activity of hepatic fructose metabolizing enzymes. There were also significant differences in fructose metabolism of liver between the male and female rats. Female rats had lower hepatic ketohexokinase and triose kinase but higher triosephosphate isomerase activities compared with male rats. Male rats fed copper-deficient diets had lower aldolase B activity compared with those fed copper-adequate diets. Female rats fed copper-deficient diets had higher triosephosphate isomerase activity compared with rats fed copper-adequate diets. Our data suggest that gender differences in hepatic fructose metabolism may not be the primary reason for the severity of copper deficiency syndrome in male rats fed copper-deficient diet with fructose.