Very low-carbohydrate diet with higher protein ratio improves lipid metabolism and inflammation in rats with diet-induced nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, and it is mainly treated through lifestyle modifications. The very low-carbohydrate diet (VLCD) can help lose weight rapidly but the possible effects of extreme dietary patterns on lipid metabolism and inflammatory responses in individuals with NAFLD remain debatable. Moreover, VLCD protein content may affect its effectiveness in weight loss, steatosis, and inflammatory responses. Therefore, we investigated the effects of VLCDs with different protein contents in NAFLD rats and the mechanisms underlying these effects. After a 16-week inducing period, the rats received an isocaloric normal diet (NC group) or a VLCD with high or low protein content (NVLH vs. NVLL group, energy ratio:protein/carbohydrate/lipid=20/1/79 vs. 6/1/93) for the next 8 weeks experimental period. We noted that the body weight decreased in both the NVLH and NVLL groups; nevertheless, the NVLH group demonstrated improvements in ketosis. The NVLL group led to hepatic lipid accumulation, possibly by increasing very-low-density lipoprotein receptor (VLDLR) expression and elevating liver oxidative stress, subsequently activating the expression of Nrf2, and inflammation through the TLR4/TRIF/NLRP3 and TLR4/MyD88/NF-κB pathway. The NVLH was noted to prevent the changes in VLDLR and the TLR4-inflammasome pathway partially. The VLCD also reduced the diversity of gut microbiota and changed their composition. In conclusion, although low-protein VLCD consumption reduces BW, it may also lead to metabolic disorders and changes in microbiota composition; nevertheless, a VLCD with high protein content may partially alleviate these limitations.

Consumption of Dehulled Adlay Improved Lipid Metabolism and Inflammation in Overweight and Obese Individuals after a 6-Week Single-Arm Pilot Study.

Obesity is a major public health concern worldwide with a rising prevalence. Diets containing whole grains have been demonstrated to benefit body composition and inflammatory conditions in individuals at a high risk of metabolic disorders. This study investigated the effects of dehulled adlay on blood lipids and inflammation in overweight and obese adults. We recruited 21 individuals with abdominal obesity to participate in a 6-week experiment, providing them 60 g of dehulled adlay powder per day as a substitute for their daily staple. Before and after the 6-week intervention, we performed anthropometric analyses and measured blood lipid profiles, adipokines, and markers of inflammation. At the end of the study, the percentage of body fat mass, blood total cholesterol, and triglyceride levels were significantly decreased compared with the baseline. Plasma tumor necrosis factor alpha, interleukin-6, leptin, and malondialdehyde levels were also reduced. In addition, participants with higher basal blood lipid levels exhibited enhanced lipid lowering effects after the dehulled adlay intervention. These results suggest that a dietary pattern containing 60 g of dehulled adlay per day may have a beneficial effect on lipid profiles and inflammatory markers in individuals that are overweight and obese.

Diet containing dehulled adlay ameliorates hepatic steatosis, inflammation and insulin resistance in rats with non-alcoholic fatty liver disease.

Dietary modification plays a vital role in the treatment of non-alcoholic liver diseases. We investigated the effects of the consumption of a different amount of dehulled adlay, which has hypolipidaemic and anti-inflammatory properties, on non-alcoholic fatty liver disease (NAFLD). We fed rats a high-fat-high-fructose liquid diet for 16 weeks to induce NAFLD. The rats were divided into three groups fed the NAFLD diet only (NN) or a diet containing 44·9 or 89·8 g/l of dehulled adlay (NA and NB groups, respectively). After 8 weeks, the NA and NB groups had lower C-reactive protein levels and improvement in insulin resistance. In addition, the NB group had lower liver weight and hepatic TAG and cholesterol concentrations than did the NN group. Compared with the NN group, the high-dose NB group had improved steatosis, lower hepatic TNF-α, IL-1ß and IL-6 levels and lower adipose leptin levels. Our results suggest that a diet containing dehulled adlay can ameliorate NAFLD progression by decreasing of insulin resistance, steatosis and inflammation.

Dehulled Adlay Consumption Modulates Blood Pressure in Spontaneously Hypertensive Rats and Overweight and Obese Young Adults.

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group's systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.

Hylocereus polyrhizus Peel Extract Retards Alcoholic Liver Disease Progression by Modulating Oxidative Stress and Inflammatory Responses in C57BL/6 Mice.

Alcoholic liver disease (ALD) has become a health problem as alcohol consumption has increased annually. Hepatic lipid accumulation, oxidative stress, and inflammation are important factors in the progression of ALD. Red pitaya (Hylocereus polyrhizus (Weber) Britt. & Rose) peel is rich in polyphenols and betanins, which possess antioxidative and anti-inflammatory properties. Therefore, the aim of this study was to investigate the effects of red pitaya peel extract (PPE) on ALD and explore the associated mechanisms. C57BL/6 J mice were administered an ethanol liquid diet for 11 weeks with or without two different doses of PPE (500 and 1000 mg/kg BW). PPE treatment significantly ameliorated liver injury and hepatic fat accumulation, and it improved hepatic lipid metabolism via increases in AMPK and PPAR-α protein expression and a decrease in SREBP-1 expression. In addition, PPE inhibited CYP2E1 and Nrf2 protein expression, reduced endotoxin levels in the serum, and decreased TLR4 and MyD88 expression and inflammatory cytokine TNF-α and IL-1ß levels in the liver. In conclusion, these findings suggest that PPE may prevent the progression of ALD by modulating lipid metabolism and reducing oxidative stress and inflammatory responses.

Crude extract of Camellia oleifera pomace ameliorates the progression of non-alcoholic fatty liver disease via decreasing fat accumulation, insulin resistance and inflammation.

Consumption of a high-fat diet increases fat accumulation and may further lead to inflammation and hepatic injuries. The aim of the study was to investigate the effects of Camellia oleifera seed extract (CSE) on non-alcoholic fatty liver disease (NAFLD). After a 16-week NAFLD-inducing period, rats were assigned to experimental groups fed an NAFLD diet with or without CSE. At the end of the study, we found that consuming CSE decreased the abdominal fat weight and hepatic fat accumulation and modulated circulating adipokine levels. We also found that CSE groups had lower hepatic cytochrome P450 2E1 and transforming growth factor (TGF)-ß protein expressions. In addition, we found that CSE consumption may have affected the gut microbiota and reduced toll-like receptor (TLR)-4, myeloid differentiation primary response gene 88, toll/IL-1 receptor domain-containing adaptor-inducing interferon-ß (TRIF) expression and proinflammatory cytokine concentrations in the liver. Our results suggest that CSE may alleviate the progression of NAFLD in rats with diet-induced steatosis through reducing fat accumulation and improving lipid metabolism and hepatic inflammation.

Antroquinonol Attenuated Abdominal and Hepatic Fat Accumulation in Rats Fed an Obesogenic Diet.

An imbalance of energy intake and expenditure leads to fat accumulation and metabolic disorders. The aim of the study was to investigate the effects of antroquinonol on diet-induced obesity. Thirty-two rats were divided into a control group (C), an obesogenic group (OB), and two experimental groups consuming 25 (OB-AQ25) and 50 mg/kg (OB-AQ50) antroquinonol (n = 8). After a 12-week experimental period, we collected blood, liver, abdominal fat, and gastrocnemius muscle tissue for analysis. The obesogenic diet induced greater weight gain and fat accumulation, and increased hepatic lipids, and tumor necrosis factor-α and interleukin-1ß concentrations in rats. Antroquinonol consumption reduced epididymal and hepatic lipids and inflammatory cytokines. We found that antroquinonol upregulated hepatic adenosine monophosphate-activated protein kinase and downregulated sterol regulatory element-binding protein-1 protein expressions and downregulated fatty acid synthase mRNA expression. In addition, gastrocnemius fibronectin type III domain containing 5 protein expression was also higher in the B group. In conclusion, our results suggested that consuming antroquinonol may ameliorate diet-induced abdominal and hepatic fat accumulation. PRACTICAL APPLICATION: Antroquinonol is a bioactive compound derived from Antrodia camphorate which is traditionally used in Chinese medicinal cuisine, and is used for developing functional foods in Taiwan. This is the first study investigating the possible effects of antroquinonol on obesity and we found that antroquinonol can ameliorate diet-induced obesity, and therefore may be used in further studies and functional food development.

Camellia Oleifera Seed Extract Mildly Ameliorates Carbon Tetrachloride-Induced Hepatotoxicity in Rats by Suppressing Inflammation.

The objective of this study was to evaluate the effects of a hot-water extract of defatted Camellia oleifera seeds (CSE) in carbon tetrachloride (CCl4 )-induced liver damage in rats. Wistar rats were separated into four groups including the normal (N) and CCl4 control (C) groups, which are fed a control diet, and the CCL (low-dose CSE) and CCH (high-dose CSE) groups, which are fed with a control diet plus different amount of CSE for an 8-week experimental period. Liver injury in the C, CCL, and CCH groups was induced by injecting CCl4 (i.p.) twice a week from the 5th week to the end of the study. In CCl4 -treated rats, the alanine transaminase (ALT) and aspartate transaminase (AST) activities and malondialdehyde (MDA) concentration significantly increased compared to the normal group. Lower antioxidative enzyme activities and higher proinflammatory cytokines, transforming growth factor-ß (TGF-ß) and hydroxyproline concentrations in the liver were also found in the CCl4 -treated group compared to the normal group. In contrast, the administration of CSE alleviated the biochemical and histopathological changes including inflammation, liver cell damage, and fibrosis caused by CCl4 in rats. Our results indicated that CSE exhibited hepatoprotective effects in CCl4 -induced liver hepatotoxicity through alleviating hepatic inflammation and fibrosis in rats. PRACTICAL APPLICATION: Camellia oleifera are widely used for edible oil production while the defatted seeds pomace is often discarded. We found that extract of C. oleifera pomace containing phenolic compounds, saponins, and polysaccharides showed protective effects chemical-driven liver damage and, therefore, may be used in further studies and developing functional foods.

Camellia oleifera seed extract attenuated abdominal and hepatic fat accumulation in rats fed a high-fat diet.

The objective of this study was to evaluate the effects of the hot-water extract of defatted Camellia oleifera seeds (CSE) on body and liver fat accumulation in rats. Forty rats were divided into 5 groups and each group was fed either an isocaloric control diet or a high-fat liquid diet with 0% (H), 0.12% (H1), 0.24% (H2), or 0.48% CSE (H3) for 8 weeks. Ingestion of the high-fat liquid diet increased abdominal and liver fat accumulation, although no difference was found in body weights compared with rats fed the control diet. We found that rats fed the H2 and H3 diets had lower plasma alanine aminotransferase activities than the H group in the fourth and eighth weeks. At the end of the study, the H2 and H3 groups also had lower epididymal and retroperitoneal fat masses, and all CSE groups had lower circulatory leptin levels than the H group. CSE consumption decreased hepatic fat accumulation in terms of liver triglycerides and a histopathology analysis, and ameliorated high-fat diet-induced elevation of hepatic tumor necrosis factor-α levels. We also found that CSE groups had lower malondialdehyde and hydroxyproline levels in the liver. Our results suggested that CSE may exert beneficial effects through decreasing body fat accumulation and hepatic steatosis and regulating adipokine levels in diet-induced nonalcoholic fatty liver disease.

Renoprotective Effects of Antroquinonol in Rats with Nω-Nitro-l-Arginine Methyl Ester-Induced Hypertension.

Endothelial dysfunction leads to elevation of blood pressure and vascular remodeling, which may result in tissue injuries. The aim of this study was to investigate the mechanisms and effects of antroquinonol on hypertension and related renal injuries. Rats were fed water containing 25 mg/kg/day Nω-nitro-l-arginine methyl ester (L-NAME) to induce hypertension, and a diet with or without antroquinonol (20 or 40 mg/kg/day) for a 9-week experiment. During the experimental period, antroquinonol reduced the elevation of systolic and diastolic blood pressure. At the end of the study, we found that the antroquinonol groups had lower serum creatinine, renal endothelin-1, angiotensin II, and malondialdehyde levels and arteriole thickening. We found that the 40 mg/kg/day antroquinonol group had lower renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activities, greater nuclear factor erythroid-2, and heme oxygenase-1 expressions. Moreover, we also found that antroquinonol decreased proinflammatory cytokine concentrations in the kidney by modulating the nuclear factor-κB pathway. These results suggest that antroquinonol may ameliorate hypertension and improve renal function by reducing oxidative stress and inflammation in rats with endothelial dysfunction.

Polyphenols with antiglycation activity and mechanisms of action: A review of recent findings.

Advanced glycation end products (AGEs) are substances composed of amino groups of proteins and reducing sugars. The initial and propagation phases of the glycation process are accompanied by the production of a large amount of free radicals, carbonyl species, and reactive dicarbonyl species, of which, methylglyoxal (MG) is the most reactive and can cause dicarbonyl stress, influencing normal physiological functions. In the advanced phase, the production of AGEs and the interaction between AGEs and their receptor, RAGE, are also considered to be among the causes of chronic diseases, oxidative stress, and inflammatory reaction. Till date, multiple physiological activities of polyphenols have been confirmed. Recently, there have been many studies discussing the ability of polyphenols to suppress the MG and AGEs formation, which was also confirmed in some in vivo studies. This review article collects recent literatures concerning the effects of polyphenols on the generation of MG and AGEs through different pathways and discusses the feasibility of the inhibition of glycative stress and dicarbonyl stress by polyphenols.

Long-term administration of advanced glycation end-product stimulates the activation of NLRP3 inflammasome and sparking the development of renal injury.

The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys. Results showed that administration of methylglyoxal-bovine serum albumin (MG-BSA) AGE accelerated renal MG, carboxyethyl lysine, carboxymethyl lysine and malondialdehyde formation and, in parallel, the levels of serum creatinine and blood urea nitrogen (BUN) were significantly increased. Expression of RAGE and NLRP3 inflammasome-related proteins (TXNIP, NLRP3, procaspase-1 and caspase-1) and IL (interleukin)-1ß secretion were upregulated, whereas the levels of EPCs, eNOS and NO were lower in MG-BSA-treated mice. This induction by MG-BSA was significantly inhibited by RAGE antagonist. Our results firstly reveal a possible mechanism of AGE-mediated renal dysfunction upon NLRP3 inflammasome activation. Therapeutic blockade of RAGE may ameliorate renal and endothelial functions in subjects under high AGE burden.

Soy ß-conglycinin retards progression of diabetic nephropathy via modulating the insulin sensitivity and angiotensin-converting enzyme activity in rats fed with high salt diet.

Soy protein was known to have renal-protective effects. The aim of this study was to investigate the effects of different doses of soybean ß-conglycinin, one of the main storage proteins in soy, on diabetic nephropathy in the rat. We used 40 Wistar rats with eight rats in each group. Diabetes mellitus was induced in rats by an intravenous injection of streptozotocin. The groups included a control group (Ctrl) fed with the standard AIN93-M diet, while other groups were fed with AIN-93M with the addition of NaCl to induce diabetic nephropathy (DN). DN rats were divided into the DN control (DN) group, the soy protein (DN + SP) group, the low-dose ß-conglycinin (DN + B) group, and the high-dose ß-conglycinin (DN + 2B) group. After a 27 weeks experimental period, we found that soy protein and ß-conglycinin decreased blood glucose via increasing the insulin sensitivity, with an enhanced cholesterol-lowering effect of ß-conglycinin-mediated hepatic LDL receptor protein expression. Otherwise, there were beneficial effects of soy protein and ß-conglycinin on renal function markers. Through the inhibition of angiotensin-converting enzyme (ACE), soy protein and ß-conglycinin retarded the progression of diabetic nephropathy by decreasing the blood pressure and histological changes. In conclusion, soy protein and ß-conglycinin may retard the progression of diabetic nephropathy by increasing insulin sensitivity, regulating lipid metabolism, improving renal function markers, and inhibiting ACE activity.

Beneficial effects of ß-conglycinin on renal function and nephrin expression in early streptozotocin-induced diabetic nephropathy rats.

The objective of the present study was to investigate the effects of ß-conglycinin and soya isoflavones on diabetic nephropathy (DN). DN was induced by an intravenous injection of streptozotocin (25 mg/kg) in spontaneously hypertensive rats. DN rats were divided into a non-diabetic group (C, control group) and three DN groups (D, DN with control diet; B, DN+control diet with one-eighth of casein replaced by ß-conglycinin as the protein source; and I, DN+control diet with 0·01 % soya isoflavones). After a 4-week experimental period, we found that fasting blood sugar and plasma and kidney advanced glycation end product levels and 24 h urinary protein excretion of the B group were significantly lower than those of the D group and insulin sensitivity and nephrin expression of the B group were significantly higher than those of the D group. In addition, systolic blood pressure, angiotensin-converting enzyme activity, angiotensin II level and plasma TAG level of the B group were significantly lower than those of the D group, whereas only the levels of plasma TAG and thiobarbituric acid-reactive substances of the I group were lower than those of the D group. In conclusion, ß-conglycinin may be beneficial for retarding DN progression and this effect cannot be completely explained by its isoflavone content.