Administration of Linoleoylethanolamide Reduced Weight Gain, Dyslipidemia, and Inflammation Associated with High-Fat-Diet-Induced Obesity.

Acylethanolamides (NAEs) are bioactive lipids derived from diet fatty acids that modulate important homeostatic functions, including appetite, fatty acid synthesis, mitochondrial respiration, inflammation, and nociception. Among the naturally circulating NAEs, the pharmacology of those derived from either arachidonic acid (Anandamide), oleic acid (OEA), and palmitic acid (PEA) have been extensively characterized in diet-induced obesity. For the present work, we extended those studies to linoleoylethanolamide (LEA), one of the most abundant NAEs found not only in plasma and body tissues but also in foods such as cereals. In our initial study, circulating concentrations of LEA were found to be elevated in overweight humans (body mass index (BMI, Kg/m2) > 25) recruited from a representative population from the south of Spain, together with AEA and the endocannabinoid 2-Arachidonoyl glycerol (2-AG). In this population, LEA concentrations correlated with the circulating levels of cholesterol and triglycerides. In order to gain insight into the pharmacology of LEA, we administered it for 14 days (10 mg/kg i.p. daily) to obese male Sprague Dawley rats receiving a cafeteria diet or a standard chow diet for 12 consecutive weeks. LEA treatment resulted in weight loss and a reduction in circulating triglycerides, cholesterol, and inflammatory markers such as Il-6 and Tnf-alpha. In addition, LEA reduced plasma transaminases and enhanced acetyl-CoA-oxidase (Acox) and Uncoupling protein-2 (Ucp2) expression in the liver of the HFD-fed animals. Although the liver steatosis induced by the HFD was not reversed by LEA, the overall data suggest that LEA contributes to the homeostatic signals set in place in response to diet-induced obesity, potentially contributing with OEA to improve lipid metabolism after high fat intake. The anti-inflammatory response associated with its administration suggests its potential for use as a nutrient supplement in non-alcoholic steatohepatitis.

Effect of (poly)phenol-rich 'Daux Belan' apple supplementation on diet-induced obesity and glucose intolerance in C57BL/6NCrl mice.

Obesity is a state of metabolic dysfunction that can lead to dyslipidemia and impaired glucose homeostasis. Apple polyphenols have been shown to ameliorate dyslipidemia/metabolic dysfunction in humans. The influence of apple (poly)phenols on energy metabolism in high-fat (HF) diet-induced obese mice remains controversial. This study examined the effect of dietary supplementation of (poly)phenol-rich 'Daux Belan' apple (DB; 6.2 mg gallic acid equivalence (GAE)/mouse/day; 0.15% (poly)phenol) in the form of freeze-dried powder on glucose and lipid metabolism in male HF-fed C57BL/6NCrl mice, in comparison to low-(poly)phenol-containing 'Zestar' apple (Z; 0.4 mg GAE/mouse/day). Obesity, glucose intolerance, hypertriglyceridemia, and hepatic lipid vacuolation were induced by HF feeding while circulating cholesterol levels remained unchanged. DB apple supplementation did not protect against HF-induced body weight gain, hyperglycemia, hepatic triglyceride level elevation, and hepatic lipid vacuolation at the tested dosage. Future studies should be conducted with increased DB dosage and employ apple (poly)phenols supplemented in the form of extracts or sugar-free powder.

Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia.

Gyejibongnyeong-hwan (GBH), a traditional Chinese medicine, is used in clinical practice to treat blood stasis in metabolic diseases. Herein, we examined the effects of GBH on dyslipidemia and investigated the underlying mechanisms by focusing on modulation of the gut microbiota-bile acid axis by GBH. We utilized a Western diet-induced dyslipidemia mouse model and divided animals into the following four groups (n = 5 each): the normal chow diet, vehicle control (WD), simvastatin (Sim, 10 mg/kg/day simvastatin; positive control), and GBH (GBH, 300 mg/kg/day) groups. The drugs were administered for 10 weeks, and morphological changes in the liver and aorta were analyzed. The mRNA expression of genes related to cholesterol metabolism, gut microbiota, and bile acid profiles were also evaluated. The GBH group showed significantly lower levels of total cholesterol, accumulation of lipids, and inflammatory markers in the liver and aorta of Western diet-fed mice. Low-density lipoprotein cholesterol levels were significantly lower in the GBH group than in the WD group (P < 0.001). The expression of cholesterol excretion-associated genes such as liver X receptor alpha and ATP-binding cassette subfamily G member 8, as well as the bile acid synthesis gene cholesterol 7 alpha-hydroxylase, which lowers cholesterol in circulation, was increased. Furthermore, GBH inhibited the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 signaling pathway through the interactions of gut microbiota with bile acids acting as FXR ligands, which included chenodeoxycholic acid and lithocholic acid. Overall, GBH improved dyslipidemia induced by a Western diet by modulating the gut microbiota-bile acid axis.

Formulation, and optimization of transdermal Atorvastatin Calcium-Loaded Ultra-flexible vesicles; ameliorates poloxamer 407-caused dyslipidemia.

Atorvastatin calcium (AC), a cholesterol-lowering medication, has limited oral bioavailability (14 %) and adverse impacts on the gastrointestinal tract (GIT), liver, and muscle. So, in an effort to improve the poor availability and overcome the hepatotoxicity complications attendant to peroral AC administration, transdermal transfersomal gel (AC-TFG) was developed as a convenient alternative delivery technique. The impact of utilizing an edge activator (EA) and varying the phosphatidylcholine (PC): EA molar ratio on the physico-chemical characteristics of the vesicles was optimized through a Quality by Design (QbD) strategy. The optimal transdermal AC-TFG was tested in an ex-vivo permeation study employing full-thickness rat skin, Franz cell experiments, an in-vivo pharmacokinetics and pharmacodynamics (PK/PD) evaluation, and a comparison to oral AC using poloxamer-induced dyslipidemic Wister rats. The optimized AC-loaded TF nanovesicles predicted by the 23-factorial design strategy had a good correlation with the measured vesicle diameter of 71.72 ± 1.159 nm, encapsulation efficiency of 89.13 ± 0.125 %, and cumulative drug release of 88.92 ± 3.78 % over 24 h. Ex-vivo data revealed that AC-TF outperformed a free drug in terms of permeation. The pharmacokinetic parameters of optimized AC-TFG demonstrated 2.5- and 13.3-fold significant improvements in bioavailability in comparison to oral AC suspension (AC-OS) and traditional gel (AC-TG), respectively. The transdermal vesicular technique preserved the antihyperlipidemic activity of AC-OS without increasing hepatic markers. Such enhancement was proven histologically by preventing the hepatocellular harm inflicted by statins. The results showed that the transdermal vesicular system is a safe alternative way to treat dyslipidemia with AC, especially when given over a long period of time.

Association between equol producers and type 2 diabetes mellitus among Japanese older adults.

AIMS/INTRODUCTION: Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non-producers and type 2 diabetes. MATERIALS AND METHODS: The participants included 147 patients with type diabetes mellitus aged 70-89 years, and 147 age- and sex-matched controls. To ascertain the equol producers or non-producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut-off value -1.75). RESULTS: The urinary equol concentration was significantly lower in the diabetes group compared with the non-diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non-diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non-diabetes group (52.8%; P < 0.01). Additionally, the frequency of dyslipidemia in female equol producers was significantly lower than that in female non-equol producers (P < 0.01). Among men, no such differences were observed. We found a significant positive correlation between the urinary equol and daidzein concentrations among equol producers (r = 0.55, P < 0.01). CONCLUSIONS: Our study findings showed that postmenopausal women had a low proportion of equol producers with diabetes and dyslipidemia.

Saccharified and Fermented Helianthus tuberosus L. Beverage Attenuates High-Fat Diet-Inducible Metabolic Complications in C57BL/6 Mice.

The prevalence of obesity has been recognized as a major public health issue with rapid increase globally. Obesity triggers other metabolic complications, such as diabetes, dyslipidemia, liver diseases, and cardiovascular diseases. Helianthus tuberosus L. (the Jerusalem artichoke) is an important edible plant that may provide health benefits in treating metabolic diseases. In this study, we investigated potential antiobesity effects of saccharified H. tuberosus L. (SH) and its fermented vinegar (fermented H. tuberosus L. [FH]) in a high-fat diet (HFD)-induced obesity murine model. FH exhibited significantly lower pH, Brix, and total sugar content compared with the SH, along with higher radical-scavenging activity. The body weight and adipose tissue weights were significantly decreased with the administration of SH and FH compared with the HFD group. SH and FH groups significantly attenuated hepatomegaly and lipid accumulation. The increased triglyceride (TG) content in obese mice was remarkably lower in the SH and FH groups. SH and FH alleviated serum dyslipidemia and atherogenic risk. Furthermore, expression of adipogenic genes was significantly downregulated after SH and FH supplementation compared with the HFD group. The TG and total cholesterol (TC) content of serum and adipose tissues significantly decreased by SH and FH administration in comparison with the HFD group. Reduced adiposity with SH and FH administration was confirmed by reduced adipocyte size and weight with inhibition of lipoprotein lipase expression. Our study showed that SH and FH, indeed FH was superior to SH, had antiobesity effects by decreasing adiposity, regulating dyslipidemia in systemic tissues, and inhibiting adipogenic gene expression.

Antihyperlipidemic potential of dietary supplementation with carnosine in high-fat diet-fed rats.

OBJECTIVE: The aim of this study was to investigate the hypolipidemic effects of carnosine and a commercial carnosine supplement on lipid status, liver and kidney function, and inflammation associated with dyslipidemia in rats with high-fat diet-induced hyperlipidemia. MATERIALS AND METHODS: The study was conducted on adult male Wistar rats, divided into control and experimental groups. Animals were kept in standard laboratory conditions and according to groups were treated with saline, carnosine, carnosine dietary supplement, simvastatin, and their combinations. All substances were prepared fresh every day and used by oral gavage. RESULTS: Treatment with a carnosine-based supplement significantly improved total and LDL cholesterol levels in serum, especially in the combination with simvastatin as a conventional drug in dyslipidemia treatment. The effect of carnosine on the metabolism of triglycerides was not as evident as in the case of cholesterol. Nevertheless, the values of the atherogenic index showed that the combinations of carnosine and carnosine supplement with simvastatin were the most effective in lowering this comprehensive lipid index. Dietary carnosine supplementation resulted also in anti-inflammatory effects, as demonstrated by immunohistochemical analyses. Besides, the good safety profile of carnosine in terms of its effect on liver and kidney functions was also confirmed. CONCLUSIONS: The use of carnosine supplements in preventing and/or treatment of metabolic disorders requires further investigations into the mechanisms of action and potential interactions with conventional therapy.

Beeswax Alcohol and Fermented Black Rice Bran Synergistically Ameliorated Hepatic Injury and Dyslipidemia to Exert Antioxidant and Anti-Inflammatory Activity in Ethanol-Supplemented Zebrafish.

Alcohol abuse, a global health problem, is closely associated with many pathological processes, such as dyslipidemia and cardiovascular disease. In particular, excessive alcohol consumption promotes dyslipidemia and liver damage, such as hepatic steatosis, fibrosis, and cirrhosis. Beeswax alcohol (BWA) is a natural product used for its antioxidant properties that has not been evaluated for its efficacy in alcohol-induced liver injury. In the present study, zebrafish were exposed to 1% ethanol with supplementation of 10% fermented black rice bran (BRB-F), 10% BWA, or 10% mixtures of BWA+BRB-F (MIX). The BRB-F, BWA, and MIX supplementation increased the survival rate dramatically without affecting the body weight changes. In histology of hepatic tissue, alcoholic foamy degeneration was ameliorated by the BWA or MIX supplements. Moreover, dihydroethidium (DHE) and immunohistochemistry staining suggested that the MIX supplement decreased the hepatic ROS production and interleukin-6 expression significantly owing to the enhanced antioxidant properties, such as paraoxonase. Furthermore, the MIX supplement improved alcohol-induced dyslipidemia and oxidative stress. The BWA and MIX groups showed lower blood total cholesterol (TC) and triglyceride (TG) levels with higher high-density lipoprotein-cholesterol (HDL-C) than the alcohol-alone group. The MIX group showed the highest HDL-C/TC ratio and HDL-C/TG ratio with the lowest low-density lipoprotein (LDL)-C/HDL-C ratio. In conclusion, BWA and BRB-F showed efficacy to treat alcohol-related metabolic disorders, but the MIX supplement was more effective in ameliorating the liver damage and dyslipidemia, which agrees with an enhanced antioxidant and anti-inflammatory activity exhibited by BWA/BRB-F in a synergistic manner.

Attenuation of hyperglycemia-associated dyslipidemic, oxidative, cognitive, and inflammatory crises via modulation of neuronal ChEs/NF-κB/COX-2/NOx, and hepatorenal functional deficits by the Tridax procumbens extract.

Tridax procumbens (cotton buttons) is a flowering plant with a medicinal reputation for treating infections, wounds, diabetes, and liver and kidney diseases. The present research was conducted to evaluate the possible protective effects of the T. procumbens methanolic extract (TPME) on an experimentally induced type 2 diabetes rat model. Wistar rats with streptozotocin (STZ)-induced diabetes were randomly allocated into five groups of five animals each, viz., a normal glycemic group (I), diabetic rats receiving distilled water group (II), diabetic rats with 150 (III) and 300 mg/kg of TPME (IV) groups, and diabetic rats with 100 mg/kg metformin group (V). All treatments were administered for 21 consecutive days through oral gavage. Results: Administration of the T. procumbens extract to diabetic rats significantly restored alterations in levels of fasting blood glucose (FBG), body weight loss, serum and pancreatic insulin levels, and pancreatic histology. Furthermore, T. procumbens significantly attenuated the dyslipidemia (increased cholesterol, low-density lipoprotein-cholesterol (LDL-C), triglycerides, and high-density lipoprotein (HDL) in diabetic rats), serum biochemical alterations (alanine transaminase (ALT), aspartate transaminase (AST), alanine phosphatase (ALP), blood urea nitrogen (BUN), creatinine, uric acid, and urea) and full blood count distortion in rats with STZ-induced diabetes. The TPME also improved the antioxidant status as evidenced by increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and decreased malondialdehyde (MDA); and decreased levels of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), and proinflammatory mediators including nuclear factor (NF)-κB, cyclooxygenase (COX)- 2, and nitrogen oxide (NOx) in the brain of rats with STZ-induced diabetes compared to rats with STZ-induced diabetes that received distilled water. However, TPME treatment failed to attenuate the elevated monoamine oxidases and decreased dopamine levels in the brain of rats with STZ-induced diabetes. Extract characterization by liquid chromatography mass spectrometry (LC-MS) identified isorhamnetin (retention time (RT)= 3.69 min, 8.8%), bixin (RT: 25.06 min, 4.72%), and lupeol (RT: 25.25 min, 2.88%) as the three most abundant bioactive compounds that could be responsible for the bioactivity of the plant. In conclusion, the TPME can be considered a promising alternative therapeutic option for managing diabetic complications owing to its antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory effects in rats with STZ-prompted diabetes.

Nil-Surin Rice Bran Hydrolysates Improve Lipid Metabolism and Hepatic Steatosis by Regulating Secretion of Adipokines and Expression of Lipid-Metabolism Genes.

Overconsumption of a high caloric diet is associated with metabolic disorders and a heightened risk of diabetes mellitus (DM), hepatic steatosis, and cardiovascular complications. The use of functional food has received much attention as a strategy in the prevention and treatment of metabolic disorders. This present study investigated whether Nil-Surin rice bran hydrolysates (NRH) could prevent or ameliorate the progression of metabolic disorders in rats in which insulin resistance (IR) was induced by a high fat-high fructose diet (HFFD). After 10 weeks of the HFFD, the rats showed elevated fasting blood glucose (FBG), impaired glucose tolerance, dysregulation of adipokine secretion, distorted lipid metabolism such as dyslipidemia, and increased intrahepatic fat accumulation. The IR was significantly attenuated by a daily dose of NRH (100 or 300 mg/kg/day). Doses of NRH rectified adipokine dysregulation by increasing serum adiponectin and improving hyperleptinemia. Interestingly, NRH decreased intrahepatic fat accumulation and improved dyslipidemia as shown by decreased levels of hepatic triglyceride (TG) and serum TG, total cholesterol and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. In addition, a modulation of expression of lipid metabolism genes was observed: NRH prevented upregulation of the lipogenesis genes Srebf1 and Fasn. In addition, NRH enhanced the expression of fatty-acid oxidation genes, as evidenced by an increase of Ppara and Cpt1a when compared with the HFFD control group. The activities of NRH in the modulation of lipid metabolism and rectifying the dysregulation of adipokines may result in a decreased risk of DM and hepatic steatosis. Therefore, NRH may be beneficial in ameliorating metabolic disorders in the HFFD model.

Lowering n-6/n-3 Ratio as an Important Dietary Intervention to Prevent LPS-Inducible Dyslipidemia and Hepatic Abnormalities in ob/ob Mice.

Obesity is closely associated with low-grade chronic and systemic inflammation and dyslipidemia, and the consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) may modulate obesity-related disorders, such as inflammation and dyslipidemia. An emerging research question is to understand the dietary intervention strategy that is more important regarding n-3 PUFA consumption: (1) a lower ratio of n-6/n-3 PUFAs or (2) a higher amount of n-3 PUFAs consumption. To understand the desirable dietary intervention method of n-3 PUFAs consumption, we replaced lard from the experimental diets with either perilla oil (PO) or corn oil (CO) to have identical n-3 amounts in the experimental diets. PO had a lower n-6/n-3 ratio, whereas CO contained higher amounts of PUFAs; it inherently contained relatively lower n-3 but higher n-6 PUFAs than PO. After the 12-week dietary intervention in ob/ob mice, dyslipidemia was observed in the normal chow and CO-fed ob/ob mice; however, PO feeding increased the high density lipoprotein-cholesterol (HDL-C) level; further, not only did the HDL-C level increase, the low density lipoprotein-cholesterol (LDL-C) and triglyceride (TG) levels also decreased significantly after lipopolysaccharide (LPS) injection. Consequently, extra TG accumulated in the liver and white adipose tissue (WAT) of normal chow- or CO-fed ob/ob mice after LPS injection; however, PO consumption decreased serum TG accumulation in the liver and WAT. PUFAs replacement attenuated systemic inflammation induced by LPS injection by increasing anti-inflammatory cytokines but inhibiting pro-inflammatory cytokine production in the serum and WAT. PO further decreased hepatic inflammation and fibrosis in comparison with the ND and CO. Hepatic functional biomarkers (aspartate aminotransferase (AST) and alanine transaminase (ALT) levels) were also remarkably decreased in the PO group. In LPS-challenged ob/ob mice, PO and CO decreased adipocyte size and adipokine secretion, with a reduction in phosphorylation of MAPKs compared to the ND group. In addition, LPS-inducible endoplasmic reticulum (ER) and oxidative stress decreased with consumption of PUFAs. Taken together, PUFAs from PO and CO play a role in regulating obesity-related disorders. Moreover, PO, which possesses a lower ratio of n-6/n-3 PUFAs, remarkably alleviated metabolic dysfunction in LPS-induced ob/ob mice. Therefore, an interventional trial considering the ratio of n-6/n-3 PUFAs may be desirable for modulating metabolic complications, such as inflammatory responses and ER stress in the circulation, liver, and/or WAT.

Partial Replacement of High-Fat Diet with Beef Tallow Attenuates Dyslipidemia and Endoplasmic Reticulum Stress in db/db Mice.

High-fat diet (HFD) consumption is closely associated with an increased risk of metabolic syndromes (MetS), such as obesity, type 2 diabetes, and cardiovascular diseases (CVDs). Therefore, the consumption of alternative and functional fatty acids to replace saturated fatty acids and/or trans-fatty acids with polyunsaturated fatty acids has become an important dietary strategy for the prevention of MetS. Consumption of omega-3 fatty acids (n-3) reduces various physiological complications, including CVDs, nonalcoholic fatty liver disease, and insulin resistance, related to inflammatory responses. In this study, we investigated the partial replacement effects of HFD with beef tallow (BT) on dyslipidemia and endoplasmic reticulum (ER) stress in male db/db mice. The animals were grouped to one of four dietary intervention groups (n = 16 per group): (1) normal diet, (2) HFD, (3) HFD partially replaced with regular beef tallow (HFD+BT1), or (4) HFD partially replaced with beef tallow containing a relatively reduced omega-6 fatty acid (n-6)/n-3 ratio (HFD+BT2) than HFD+BT1. After 6 weeks of dietary intervention, 1 mg/kg of phosphate-buffered saline or tunicamycin (TM) was injected intraperitoneally. HFD+BT2 significantly suppressed the serum total cholesterol and non-high-density lipoprotein cholesterol levels more than HFD and HFD+BT1, and triglyceride levels in the epididymal adipose tissue (EAT) were remarkably decreased. Mice that received HFD+BT2 had elevated protein expressions of phospho-AMP-activated protein kinase (p-AMPK). Moreover, HFD+BT2 effectively inhibited ER stress in the liver and EAT. Consistent with our hypothesis, HFD+BT2 remarkably alleviated dyslipidemia and TM-inducible ER stress, while activating p-AMPK.

Fish Oil Enriched n-3 Polyunsaturated Fatty Acids Improve Ketogenic Low-Carbohydrate/High-Fat Diet-Caused Dyslipidemia, Excessive Fat Accumulation, and Weight Control in Rats.

Low-carbohydrate and high-fat diets have been used for body weight (BW) control, but their adverse effects on lipid profiles have raised concern. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, has profound effects on lipid metabolism. We hypothesized that FO supplementation might improve the lipid metabolic disturbance elicited by low-carbohydrate and high-fat diets. Male SD rats were randomized into normal control diet (NC), high-fat diet (HF), and low-carbohydrate/high-fat diet (LC) groups in experiment 1, and NC, LC, LC + 5% FO (5CF), and LC + 10% FO diet (10CF) groups in experiment 2. The experimental duration was 11 weeks. In the LC group, a ketotic state was induced, and food intake was decreased; however, it did not result in BW loss compared to either the HF or NC groups. In the 5CF group, rats lost significant BW. Dyslipidemia, perirenal and epididymal fat accumulation, hepatic steatosis, and increases in triglyceride and plasma leptin levels were observed in the LC group but were attenuated by FO supplementation. These findings suggest that a ketogenic low-carbohydrate/high-fat diet with no favorable effect on body weight causes visceral and liver lipid accumulation. FO supplementation not only aids in body weight control but also improves lipid metabolism in low-carbohydrate/high-fat diet-fed rats.

Bone Health in Patients with Dyslipidemias: An Underestimated Aspect.

Beyond being aging-related diseases, atherosclerosis and osteoporosis share common pathogenetic pathways implicated in bone and vascular mineralization. However, the contributory role of dyslipidemia in this interplay is less documented. The purpose of this narrative review is to provide epidemiological evidence regarding the prevalence of bone disease (osteoporosis, fracture risk) in patients with dyslipidemias and to discuss potential common pathophysiological mechanisms linking osteoporosis and atherosclerosis. The effect of hypolipidemic therapy on bone metabolism is also discussed. Despite the high data heterogeneity and the variable quality of studies, dyslipidemia, mainly elevated total and low-density lipoprotein cholesterol concentrations, is associated with low bone mass and increased fracture risk. This effect may be mediated directly by the increased oxidative stress and systemic inflammation associated with dyslipidemia, leading to increased osteoclastic activity and reduced bone formation. Moreover, factors such as estrogen, vitamin D and K deficiency, and increased concentrations of parathyroid hormone, homocysteine and lipid oxidation products, can also contribute. Regarding the effect of hypolipidemic medications on bone metabolism, statins may slightly increase BMD and reduce fracture risk, although the evidence is not robust, as it is for omega-3 fatty acids. No evidence exists for the effects of ezetimibe, fibrates, and niacin. In any case, more prospective studies are needed further to elucidate the association between lipids and bone strength.

Polar fraction from Parkinsonia aculeata aerial parts extract improves imbalanced metabolic profile and reduces proinflammatory interleukin levels in white adipose tissue in obese rats induced by western diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinsonia aculeata L. (Cesalpineaceae) is a medium tree found in the Xingó region (semi-arid area) in Northeast of Brazil, recognised by local population as an antidiabetic agent. According information from local community, the commonly traditional preparation is prepared as an infusion of the aerial part of the plant and consumed over the day to manage diabetes-related complications. Previous studies have described Parkinsonia aculeate as a product with both hypoglycemic and hypotriglyceridemic effects. AIM OF THE STUDY: The objective of this study was to evaluate the effects of polar fraction obtained from the hydroethanolic extract of Parkinsonia aculeata (PfrHEPA) on the lipid profile of animals that consumed a westernized diet. MATERIALS AND METHODS: Thirty-six Wistar rats (45-55 g) were fed either with standard control(C) or westernized diet(W) for 120 days. The food intake, body weight evolution and body size were also analyzed. From 120 to 150 days, they were orally treated according to their group with vehicle (distillated water, 10 mL/kg), PfrHEPA at three doses (35, 70 and 140 mg/kg/day) or Gemfibrozil (140 mg/kg/day) for 30 days. RESULTS: The animals fed with westernized diet showed dyslipidemia when compared to animals receiving a standard diet. Treatment with PfrHEPA (140 mg/kg), even with the continued consumption of westernized diet by animals (from 120 to 150 days) promoted a significant reduction in total cholesterol, LDL and triglyceride levels, in relation to untreated W group. PfrHEPA 140 mg/kg reduced the key serum lipids and glycaemia as well as inflammatory cytokines known as important risk factors of cardiovascular diseases. CONCLUSIONS: The observed evidence may contribute to the control of metabolic parameters as dyslipidemia corroborating the ethnopharmacological information concerning the antihyperlipidemic and hypoglycemic activities of P. aculeata.

The Interdependency and Co-Regulation of the Vitamin D and Cholesterol Metabolism.

Vitamin D and cholesterol metabolism overlap significantly in the pathways that contribute to their biosynthesis. However, our understanding of their independent and co-regulation is limited. Cardiovascular disease is the leading cause of death globally and atherosclerosis, the pathology associated with elevated cholesterol, is the leading cause of cardiovascular disease. It is therefore important to understand vitamin D metabolism as a contributory factor. From the literature, we compile evidence of how these systems interact, relating the understanding of the molecular mechanisms involved to the results from observational studies. We also present the first systems biology pathway map of the joint cholesterol and vitamin D metabolisms made available using the Systems Biology Graphical Notation (SBGN) Markup Language (SBGNML). It is shown that the relationship between vitamin D supplementation, total cholesterol, and LDL-C status, and between latitude, vitamin D, and cholesterol status are consistent with our knowledge of molecular mechanisms. We also highlight the results that cannot be explained with our current knowledge of molecular mechanisms: (i) vitamin D supplementation mitigates the side-effects of statin therapy; (ii) statin therapy does not impact upon vitamin D status; and critically (iii) vitamin D supplementation does not improve cardiovascular outcomes, despite improving cardiovascular risk factors. For (iii), we present a hypothesis, based on observations in the literature, that describes how vitamin D regulates the balance between cellular and plasma cholesterol. Answering these questions will create significant opportunities for advancement in our understanding of cardiovascular health.

Increasing the Power of Polyphenols through Nanoencapsulation for Adjuvant Therapy against Cardiovascular Diseases.

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.

Matcha Green Tea Alleviates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice by Regulating Lipid Metabolism and Inflammatory Responses.

Lately, matcha green tea has gained popularity as a beverage and food additive. It has proved to be effective in preventing obesity and related metabolic syndromes. However, the underlying mechanisms of its control effects against non-alcoholic fatty liver disease (NAFLD) are complicated and remain elusive. In the present study, we performed an in vivo experiment using male C57BL/6 mice fed with a high-fat diet and simultaneously treated with matcha for six weeks. Serum biochemical parameters, histological changes, lipid accumulation, inflammatory cytokines, and relevant indicators were examined. Dietary supplementation of matcha effectively prevented excessive accumulation of visceral and hepatic lipid, elevated blood glucose, dyslipidemia, abnormal liver function, and steatosis hepatitis. RNA sequencing analyses of differentially expressed genes in liver samples indicated that matcha treatment decreased the activity of lipid droplet-associated proteins and increased the activity of cytochrome P450 enzymes, suggesting improved metabolic capacity and liver function. The current study provided evidence for new dietary strategies based on matcha supplementation to ameliorate lipotoxicity-induced obesity and NALFD.

The Role of Essential Oils and Their Main Compounds in the Management of Cardiovascular Disease Risk Factors.

Cardiovascular diseases (CVDs) are a global health burden that greatly impact patient quality of life and account for a huge number of deaths worldwide. Despite current therapies, several side effects have been reported that compromise patient adherence; thus, affecting therapeutic benefits. In this context, plant metabolites, namely volatile extracts and compounds, have emerged as promising therapeutic agents. Indeed, these compounds, in addition to having beneficial bioactivities, are generally more amenable and present less side effects, allowing better patient tolerance. The present review is an updated compilation of the studies carried out in the last 20 years on the beneficial potential of essential oils, and their compounds, against major risk factors of CVDs. Overall, these metabolites show beneficial potential through a direct effect on these risk factors, namely hypertension, dyslipidemia and diabetes, or by acting on related targets, or exerting general cellular protection. In general, monoterpenic compounds are the most studied regarding hypotensive and anti-dyslipidemic/antidiabetic properties, whereas phenylpropanoids are very effective at avoiding platelet aggregation. Despite the number of studies performed, clinical trials are sparse and several aspects related to essential oil's features, namely volatility and chemical variability, need to be considered in order to guarantee their efficacy in a clinical setting.