Lila Missae Oyama

Dietary whey protein lessens several risk factors for metabolic diseases: a review

Obesity and type 2 diabetes mellitus (DM) have grown in prevalence around the world, and recently, related diseases have been considered epidemic. Given the high cost of treatment of obesity/DM-associated diseases, strategies such as dietary manipulation have been widely studied; among them, the whey protein diet has reached popularity because it has been suggested as a strategy for the prevention and treatment of obesity and DM in both humans and animals. Among its main actions, the following activities stand out: reduction of serum glucose in healthy individuals, impaired glucose tolerance in DM and obese patients; reduction in body weight; maintenance of muscle mass; increases in the release of anorectic hormones such as cholecystokinin, leptin, and glucagon like-peptide 1 (GLP-1); and a decrease in the orexigenic hormone ghrelin. Furthermore, studies have shown that whey protein can also lead to reductions in blood pressure, inflammation, and oxidative stress.

Polyunsaturated fatty acid-rich diets: effect on adipose tissue metabolism in rats

The aim of the present study was to evaluate the effect of diets rich in n-6 and n-3 fatty acids on adipose tissue metabolism. Starting at weaning, male Wistar rats were fed ad libitum, for 8 weeks with one of the following diets: C, rat chow; S, rat chow containing 15 % (w/w) soyabean oil; F, rat chow containing 15 % (w/w) fish oil; SF, rat chow containing 15 % (w/w) soyabean and fish oil (5:1, w/w). Casein was added to the fat diets to achieve the same 20 % (w/w) protein content as in the control chow. Food intake and body weight were measured weekly. The rats were killed by decapitation and the retroperitoneal (RET) and epididymal (EPI) white adipose tissues were removed and weighed. Tissue lipid and protein content, in vivo lipogenesis rate, uptake of diet-derived lipids, in vitro lipolytic rate, adipocyte area, lipoprotein lipase, ATP citrate lyase, and malic enzyme activities were evaluated. Carcass lipid and protein contents were also measured. Energy intake was reduced while carcass lipid content was increased in the three fat-fed groups. However, carcass protein and body weight gains were elevated only with diets F and SF. Lipolysis rate was diminished by diets F and SF, while the uptake of diet-derived lipids was elevated by the diet S in both RET and EPI tissues. These metabolic alterations may have contributed to the increase in in vivo lipogenesis rate in the presence of decreased ATP citrate lyase and malic enzyme activities induced by the three lipid diets. These results indicate that enrichment of the diet with polyunsaturated fatty acids causes changes in adipose tissue metabolism that favour fat deposition. Different metabolic pathways were preferentially affected by each type of fatty acid used.

Lipotoxicity: Effects of Dietary Saturated and Transfatty Acids

The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.

β-Hydroxy-β-methylbutyrate (HMβ) supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway

Abstractβ-Hydroxy-β-methylbutyrate (HMβ) supplementation is used to treat cancer, sepsis and exercise-induced muscle damage. However, its effects on animal and human health and the consequences of this treatment in other tissues (e.g., fat and liver) have not been examined. The purpose of this study was to evaluate the effects of HMβ supplementation on skeletal muscle hypertrophy and the expression of proteins involved in insulin signalling. Rats were treated with HMβ (320 mg/kg body weight) or saline for one month. The skeletal muscle hypertrophy and insulin signalling were evaluated by western blotting, and hormonal concentrations were evaluated using ELISAs. HMβ supplementation induced muscle hypertrophy in the extensor digitorum longus (EDL) and soleus muscles and increased serum insulin levels, the expression of the mammalian target of rapamycin (mTOR) and phosphorylation of p70S6K in the EDL muscle. Expression of the insulin receptor was increased only in liver. Thus, our results suggest that HMβ supplementation can be used to increase muscle mass without adverse health effects.

Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring

During pregnancy and/or lactation, maternal nutrition is related to the adequate development of the fetus, newborn and future adult, likely by modifications in fetal programming and epigenetic regulation. Fetal programming is characterized by adaptive responses to specific environmental conditions during early life stages, which may alter gene expression and permanently affect the structure and function of several organs and tissues, thus influencing the susceptibility to metabolic disorders. Regarding lipid metabolism during the first two trimesters of pregnancy, the maternal body accumulates fat, whereas in late pregnancy, the lipolytic activity in the maternal adipose tissue is increased. However, an excess or deficiency of certain fatty acids may lead to adverse consequences to the fetuses and newborns. Fetal exposure to trans fatty acids appears to promote early deleterious effects in the offsprings health, thereby increasing the individual risk for developing metabolic diseases throughout life. Similarly, the maternal intake of saturated fatty acids seems to trigger alterations in the liver and adipose tissue function associated with insulin resistance and diabetes. The polyunsaturated fatty acids (PUFAs), particularly long-chain PUFAs (long-chain PUFA-arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid), play an important and beneficial physiologic role in the offspring who receive this fatty acid during critical periods of development. Therefore, the maternal nutritional condition and fatty acid intake during pregnancy and/or lactation are critical factors that are strongly associated with normal fetal and postnatal development, which influence the modifications in fetal programming and in the individual risk for developing metabolic diseases throughout life.

Diets rich in polyunsaturated fatty acids: effect on hepatic metabolism in rats.

OBJECTIVE We investigated the effect of diets rich in omega-6 and omega-3 fatty acids on hepatic metabolism. METHODS Male Wistar rats, just weaned, were fed ad libitum for 8 wk with one of the following diets: rat chow (C), rat chow containing 15% (w/w) soybean oil (S), rat chow containing 15% (w/w) fish oil (F), and rat chow containing 15% soy bean and fish oil (SF; 5:1, w/w). Casein was added to the fatty diets to achieve the same content of protein (20%) as the control chow. The rats were killed by decapitation, and the hepatic tissue was removed and weighed. Tissue lipid, glycogen, and protein content, in vivo lipogenesis rate, and adenosine triphosphate citrate lyase and malic enzyme activities were evaluated. Plasma total lipids, triacylglycerol, and cholesterol concentrations were assessed. RESULTS Body weight gain was higher in F and SF than in C and S rats. Liver weight, lipid content, and lipogenesis rate increased in F and SF rats, although adenosine triphosphate citrate lyase activity decreased. Glycogen concentration decreased in S, F, and SF rats compared with C rats. Plasma total lipids and triacylglycerol concentrations were lower in F and SF than in C rats. Total and high-density lipoprotein cholesterol (HDL-C) plasma levels decreased in F rats, with maintenance of the total:HDL-C ratio. In SF rats, an increase in HDL-C led to a lower total:HDL-C ratio. CONCLUSIONS These results indicated that an enrichment of the diet with omega-3 polyunsaturated fatty acids produces hypolipidemia but may cause changes in liver metabolism that favor lipid deposition. They also suggested that the addition of a small amount of eicosapentaenoic and docosahexaenoic polyunsaturated fatty acids to an omega-6-rich diet further improve the circulating lipid profile, in comparison with an omega-3-rich diet, but it does not prevent excess liver lipid accumulation.

Both adiponectin and interleukin-10 inhibit LPS-induced activation of the NF-κB pathway in 3T3-L1 adipocytes.

Adiponectin and interleukin 10 (IL-10) are adipokines that are predominantly secreted by differentiated adipocytes and are involved in energy homeostasis, insulin sensitivity, and the anti-inflammatory response. These two adipokines are reduced in obese subjects, which favors increased activation of nuclear factor kappa B (NF-κB) and leads to elevation of pro-inflammatory adipokines. However, the effects of adiponectin and IL-10 on NF-κB DNA binding activity (NF-κBp50 and NF-κBp65) and proteins involved with the toll-like receptor (TLR-2 and TLR-4) pathway, such as MYD88 and TRAF6 expression, in lipopolysaccharide-treated 3T3-L1 adipocytes are unknown. Stimulation of lipopolysaccharide-treated 3T3-L1 adipocytes for 24h elevated IL-6 levels; activated the NF-κB pathway cascade; increased protein expression of IL-6R, TLR-4, MYD88, and TRAF6; and increased the nuclear activity of NF-κB (p50 and p65) DNA binding. Adiponectin and IL-10 inhibited the elevation of IL-6 levels and activated NF-κB (p50 and p65) DNA binding. Taken together, the present results provide evidence that adiponectin and IL-10 have an important role in the anti-inflammatory response in adipocytes. In addition, inhibition of NF-κB signaling pathways may be an excellent strategy for the treatment of inflammation in obese individuals.

Endotoxin levels correlate positively with a sedentary lifestyle and negatively with highly trained subjects.

IntroductionA sedentary lifestyle increases the risk of developing cardiovascular disease, obesity, and diabetes. This phenomenon is supported by recent studies suggesting a chronic, low-grade inflammation status. Endotoxin derived from gut flora may be key to the development of inflammation by stimulating the secretion of inflammatory factors. This study aimed to examine plasma inflammatory markers and endotoxin levels in individuals with a sedentary lifestyle and/or in highly trained subjects at rest. Methods: Fourteen male subjects (sedentary lifestyle n = 7; highly trained subjects n = 7) were recruited. Blood samples were collected after an overnight fast (~12 h). The plasmatic endotoxin, plasminogen activator inhibitor type-1 (PAI-1), monocyte chemotactic protein-1 (MCP1), ICAM/CD54, VCAM/CD106 and lipid profile levels were determined.ResultsEndotoxinemia was lower in the highly trained subject group relative to the sedentary subjects (p < 0.002). In addition, we observed a positive correlation between endotoxin and PAI-1 (r = 0.85, p < 0.0001), endotoxin and total cholesterol (r = 0.65; p < 0.01), endotoxin and LDL-c (r = 0.55; p < 0.049) and endotoxin and TG levels (r = 0.90; p < 0.0001). The plasma levels of MCP-1, ICAM/CD54 and VCAM/CD106 did not differ.ConclusionThese results indicate that a lifestyle associated with high-intensity and high-volume exercise induces favorable changes in chronic low-grade inflammation markers and may reduce the risk for diseases such as obesity, diabetes and cardiovascular diseases.

High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations

BackgroundAdiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. In addition, it increases fatty acid oxidation in the muscle and potentiates insulin inhibition of hepatic gluconeogenesis. Two adiponectin receptors have been identified: AdipoR1 is the major receptor expressed in skeletal muscle, whereas AdipoR2 is mainly expressed in liver. Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia; of note, all of these features are shared by the condition of insulin resistance. Although it has been shown that glucocorticoids inhibit adiponectin expression in vitro and in vivo, little is known about the regulation of adiponectin receptors. The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues.ResultsFeeding of a high-fat diet increased serum glucose levels and decreased adiponectin and adipoR2 mRNA expression in subcutaneous and retroperitoneal adipose tissues, respectively. Moreover, it increased both adipoR1 and adipoR2 mRNA levels in muscle and adipoR2 protein levels in liver. Adrenalectomy combined with the synthetic glucocorticoid dexamethasone treatment resulted in increased glucose and insulin levels, decreased serum adiponectin levels, reduced adiponectin mRNA in epididymal adipose tissue, reduction of adipoR2 mRNA by 7-fold in muscle and reduced adipoR1 and adipoR2 protein levels in muscle. Adrenalectomy alone increased adiponectin mRNA expression 3-fold in subcutaneous adipose tissue and reduced adipoR2 mRNA expression 2-fold in liver.ConclusionHyperglycemia as a result of a high-fat diet is associated with an increase in the expression of the adiponectin receptors in muscle. An excess of glucocorticoids, rather than their absence, increase glucose and insulin and decrease adiponectin levels.

Relationship between bone mineral density, leptin and insulin concentration in Brazilian obese adolescents

Despite the epidemic of adolescent obesity, the effect of obesity and hormones on bone mineral accrual during growth is poorly understood. Studies using dual-energy X-ray to examine the effect of obesity on bone mass in children and adolescents have yielded conflicting results. The aim of this study was to explore the combined and independent contributions of body mass index, body composition, leptin, insulin, glucose levels and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) to bone mineral density (BMD) and bone mineral content in a group of Brazilian obese adolescents. This study included 109 post-pubescent obese adolescents. A whole-body dual-energy X-ray absorptiometry scan was performed,using a HOLOGIC QDR4200, to determine whole-body BMD and body composition. Blood samples were collected in the outpatient clinic after an overnight fast, and evaluated for fasting blood glucose and immunoreactive insulin. Leptin levels were assessed with a radioimmunoassay kit. Insulin resistance was assessed by HOMA-IR and the quantitative insulin sensitivity check index. Our results showed that insulin levels and HOMA-IR correlated negatively with BMD and a linear regression analysis showed that serum leptin is inversely associated to BMD adjusted for body mass. In conclusion, our data support the hypothesis that leptin, insulin and HOMA-IR are inversely associated with BMD and play a significant direct role in bone metabolism.