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1.
Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review.
Cano, R, Pérez, JL, Dávila, LA, Ortega, Á, Gómez, Y, Valero-Cedeño, NJ, Parra, H, Manzano, A, Véliz Castro, TI, Albornoz, MPD, et al
International journal of molecular sciences. 2021;(9)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.
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2.
Efficacy of Pomegranate Seed Powder on Glucose and Lipid Metabolism in Patients with Type 2 Diabetes: A Prospective Randomized Double-Blind Placebo-Controlled Clinical Trial.
Seyed Hashemi, M, Namiranian, N, Tavahen, H, Dehghanpour, A, Rad, MH, Jam-Ashkezari, S, Emtiazy, M, Hashempur, MH
Complementary medicine research. 2021;(3):226-233
Abstract
INTRODUCTION Pomegranate is known as a functional food which has multiple health-promoting activities. It has been assessed for patients with metabolic syndrome. Specifically, an antidiabetic activity of its juice and plausible mechanisms for its action have been shown in multitudinous studies. The aim of this study was assessing the effects of complementary treatment with pomegranate seed powder (PSP) oral supplementation on patients with type 2 diabetes mellitus (T2DM). METHODS Sixty patients were treated for 8 weeks by 5 g PSP or placebo, twice daily. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol, and triglyceride (TG) were recorded as the outcome measures at the beginning and after the intervention. The findings were analyzed using the independent t test and Mann-Whitney U test. RESULTS After 8 weeks, the mean differences of FBG, HbA1c, cholesterol, and TG were significantly decreased in the PSP group when compared with the placebo group (p value <0.05). In addition, post-intervention values of FBG and HbA1c were significantly lower in patients treated with PSP compared to the placebo group (p values = 0.02 and 0.01, respectively). However, the latter comparison regarding cholesterol and TG showed no significant differences (p values = 0.51 and 0.26, respectively). CONCLUSION It seems that complementary treatment with PSP may have beneficial effects on FBG and HbA1c of patients with T2DM. However, its effect on TG and cholesterol was equivocal.
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3.
Health effects of coconut oil: Summary of evidence from systematic reviews and meta-analysis of interventional studies.
Jayawardena, R, Swarnamali, H, Ranasinghe, P, Misra, A
Diabetes & metabolic syndrome. 2021;(2):549-555
Abstract
BACKGROUND AND AIMS Systemic review (SR) and meta-analysis (MA) of interventional studies are considered as the highest level of evidence for clinical decision making. Therefore, we systematically summarized all high-quality evidence on the usage of coconut oil for health-related benefits from SRs and MA. METHODS PubMed®, Web of science®, SciVerse Scopus®, and EMBASE® databases were systematically searched to select SRs and SRs with MA of interventional studies reporting health-related clinical outcomes of coconut oil. Similar studies were grouped based on their respective clinical areas. A methodological quality appraisal was conducted for all included SRs and SRs with MA using the Critical Appraisal Checklist for Systematic Reviews. RESULTS A total of seven papers were selected for inclusion in this review, consisting of three MA and one SR on cardio-metabolic health, one SR on oral health, and one SR and one MA each on skin health. Coconut oil significantly increases serum total cholesterol, low-density- and high-density- lipoprotein cholesterol levels compared to poly- and mono-unsaturated oils. Limited studies showed that topical use of coconut oil helps in the prevention and treatment of atopic dermatitis and oil pulling for the prevention of dental caries. All four studies on cardiometabolic health and the SR on oral health had a high score in the quality assessment, SR with MA on skin health fulfilled high-quality scoring whereas the SR on the same topic had a low-quality scoring. CONCLUSIONS In summary, consistent and strong evidence shows that coconut oil has an adverse effect on the lipids parameters associated with cardio-metabolic health, with limited studies to conclude the effects of atopic dermatitis and oil pulling.
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4.
Bile acids mediated potential functional interaction between FXR and FATP5 in the regulation of Lipid Metabolism.
Kumari, A, Pal Pathak, D, Asthana, S
International journal of biological sciences. 2020;(13):2308-2322
Abstract
Perturbation in lipid homeostasis is one of the major bottlenecks in metabolic diseases, especially Non-alcoholic Fatty Liver Disease (NAFLD), which has emerged as a leading global cause of chronic liver disease. The bile acids (BAs) and their derivatives exert a variety of metabolic effects through complex and intertwined pathways, thus becoming the attractive target for metabolic syndrome treatment. To modulate the lipid homeostasis, the role of BAs, turn out to be paramount as it is essential for the absorption, transport of dietary lipids, regulation of metabolic enzymes and transporters that are essential for lipid modulation, flux, and excretion. The synthesis and transport of BAs (conjugated and unconjugated) is chiefly controlled by nuclear receptors and the uptake of long-chain fatty acids (LCFA) and BA conjugation via transporters. Among them, from in-vivo studies, farnesoid X receptor (FXR) and liver-specific fatty acid transport protein 5 (FATP5) have shown convincing evidence for their key roles in lipid homeostasis and reversal of fatty liver disease substantially. BAs have a wider range of biological effects as they are identified as modulators for FXR and FATP5 both and therefore hold a significant promise for altering the lipid content in the treatment of a metabolic disorder. BAs also have received noteworthy interest in drug delivery research due to its peculiar physicochemical properties and biocompatibility. Here, we are highlighting the connecting possibility of BAs as an agonist for FXR and antagonist for FATP5, paving an avenue to target them for designing synthetic small molecules for lipid homeostasis.
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5.
Beneficial Effects of Pomegranate on Lipid Metabolism in Metabolic Disorders.
Hou, C, Zhang, W, Li, J, Du, L, Lv, O, Zhao, S, Li, J
Molecular nutrition & food research. 2019;(16):e1800773
Abstract
Pomegranate (Punica granatum Linn) is used in the prevention and treatment of metabolic syndrome in recent decades. Imbalances in lipid metabolism are profound features of metabolic disorders. In vivo and in vitro studies have shown that extracts of different pomegranate fractions (peels, flowers, juice, and seeds) regulate lipid metabolism in metabolic-disorder-associated diseases such as atherosclerosis, nonalcoholic fatty liver disease, and type 2 diabetes, helping to alleviate the development of diseases. Amelioration of oxidative stress and the inflammatory response is considered an important reason underlying the regulation of lipid metabolism by pomegranate extracts. Mitochondria, the major cellular site for lipid oxidation, are strongly associated with cellular oxidative and inflammatory status and are likely to be a target for pomegranate extract action. This review summarizes the main findings about the effects of different pomegranate fraction extracts on lipid metabolism in metabolic-disorder-associated diseases and analyses how pomegranate extracts achieve their effects. Furthermore, it also provides an important basis for the research and development of pomegranate-related nutrients or drugs.
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6.
Ketogenic Diet: A New Light Shining on Old but Gold Biochemistry.
Longo, R, Peri, C, Cricrì, D, Coppi, L, Caruso, D, Mitro, N, De Fabiani, E, Crestani, M
Nutrients. 2019;(10)
Abstract
Diets low in carbohydrates and proteins and enriched in fat stimulate the hepatic synthesis of ketone bodies (KB). These molecules are used as alternative fuel for energy production in target tissues. The synthesis and utilization of KB are tightly regulated both at transcriptional and hormonal levels. The nuclear receptor peroxisome proliferator activated receptor α (PPARα), currently recognized as one of the master regulators of ketogenesis, integrates nutritional signals to the activation of transcriptional networks regulating fatty acid β-oxidation and ketogenesis. New factors, such as circadian rhythms and paracrine signals, are emerging as important aspects of this metabolic regulation. However, KB are currently considered not only as energy substrates but also as signaling molecules. β-hydroxybutyrate has been identified as class I histone deacetylase inhibitor, thus establishing a connection between products of hepatic lipid metabolism and epigenetics. Ketogenic diets (KD) are currently used to treat different forms of infantile epilepsy, also caused by genetic defects such as Glut1 and Pyruvate Dehydrogenase Deficiency Syndromes. However, several researchers are now focusing on the possibility to use KD in other diseases, such as cancer, neurological and metabolic disorders. Nonetheless, clear-cut evidence of the efficacy of KD in other disorders remains to be provided in order to suggest the adoption of such diets to metabolic-related pathologies.
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7.
A pre-meal of whey proteins induces differential effects on glucose and lipid metabolism in subjects with the metabolic syndrome: a randomised cross-over trial.
Bjørnshave, A, Holst, JJ, Hermansen, K
European journal of nutrition. 2019;(2):755-764
Abstract
PURPOSE Postprandial lipaemia (PPL), an independent risk factor for cardiovascular disease, is affected by composition and timing of meals. We evaluated if whey proteins (WP) consumed as a pre-meal before a fat-rich meal reduce postprandial triglyceride (TG) and apolipoprotein B-48 (ApoB-48) responses in subjects with the metabolic syndrome (MeS). METHODS An acute, randomised, cross-over trial was conducted. 20 subjects with MeS consumed a pre-meal of 0, 10 or 20 g WP 15 min prior to a fat-rich meal. The responses of TG and ApoB-48 were assessed. We also analysed postprandial responses of free fatty acids (FFA), glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and paracetamol (reflecting gastric emptying rates). RESULTS WP pre-meal did not alter the TG or ApoB-48 responses. In contrast, the insulin response was more pronounced after a pre-meal of 20 g WP than with 10 g WP (P = 0.0005) and placebo (P < 0.0001). Likewise, the postprandial glucagon response was greater with a pre-meal of 20 g WP than with 10 g WP (P < 0.0001) and 0 g WP (P < 0.0001). A pre-meal with 20 g of WP generated lower glucose (P = 0.0148) and S-paracetamol responses (P = 0.0003) and a higher GLP-1 response (P = 0.0086) than placebo. However, the pre-meal did not influence responses of GIP, FFA or appetite assessed by a Visual Analog Scale. CONCLUSIONS Consumption of a WP pre-meal prior to a fat-rich meal did not affect TG and chylomicron responses. In contrast, the WP pre-meal stimulates insulin and glucagon secretion and reduces blood glucose as expected, and delays gastric emptying. Consequently, our study points to a differential impact of a WP pre-meal on lipid and glucose metabolism to a fat-rich meal in subjects with MeS.
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8.
Efficacy of a nutraceutical combination on lipid metabolism in patients with metabolic syndrome: a multicenter, double blind, randomized, placebo controlled trial.
Galletti, F, Fazio, V, Gentile, M, Schillaci, G, Pucci, G, Battista, F, Mercurio, V, Bosso, G, Bonaduce, D, Brambilla, N, et al
Lipids in health and disease. 2019;(1):66
Abstract
BACKGROUND Nutraceuticals represent a new therapeutic frontier in the treatment of metabolic syndrom (MetS) and related cardiovascular risk factors. The aim of this study was to evaluate the potential beneficial effects of Armolipid Plus (AP) (berberine 500 mg, red yest rice, monacolin K 3 mg and policosanol 10 mg) on insulin resistance, lipid profile, particularly on small and dense LDL cholesterol (sdLDL-C), representing the most atherogenic components, as well as its effects on high sensitivity C-reactive protein, a notable marker of cardiovascular risk, blood pressure and cardiac remodeling in subjects affected by MetS, with left ventricular hypertrophy. METHODS The study was a prospective, multi-center, randomized, double blind, placebo-controlled trial. One hundred and fifty eight patients, aged between 28 and 76 years old, were enrolled and randomized to receive either one tablet of AP or placebo (PL) once daily for 24 weeks. Anthropometric and vital parameters, total cholesterol (tot-C), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceridemia (TG), non-HDL cholesterol (NHDL-C) and sdLDL-C were evaluated. RESULTS After 24 weeks of treatment, the analysis performed on 141 subjects (71 in AP arm and 70 in PL arm), showed a significant improvement of lipid profile in the AP group, with reduction in tot-C (- 13.2 mg/dl), LDL-C (- 13.9 mg/dl) and NHDL-C (- 15.3 mg/dl) and increase in HDL-C (+ 2.0 mg/dl). These changes were equally significant compared with placebo (tot-C: AP - 13.2 mg/dL vs PL + 2.7 mg/dL, p < 0.01; LDL-C: AP -13.9 mg/dl vs PL + 1.5 mg/dl, p < 0.01; NHDL-C: AP -15.3 mg/dl vs PL + 2.8 mg/dl, p < 0.01), Although no significant difference was observed between the two arms in the reduction of HDL-C nevertheless it increased significantly in the AP group (AP + 2 mg/dL p < 0.05, PL 0.13 mg/dL). CONCLUSION The results of this study, applicable to a specific local population show that, in a population of subjects affected by MetS, treatment with AP improves the lipid profile and the most atherogenic factors, thus suggesting a reduction in the risk of development and progression of atherosclerosis, particularly in subjects with high atherogenic risk, due to the presence of sdLDL-C.
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9.
Comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial.
Shokrpour, M, Foroozanfard, F, Afshar Ebrahimi, F, Vahedpoor, Z, Aghadavod, E, Ghaderi, A, Asemi, Z
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2019;(5):406-411
Abstract
This investigation was conducted to evaluate comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome (PCOS). This randomized controlled trial was conducted on 53 women with PCOS, aged 18-40 years old. Subjects were randomly allocated into two groups to take either myo-inositol (n = 26) or metformin (n = 27) for 12 weeks. Myo-inositol supplementation, compared with metformin, significantly reduced fasting plasma glucose (FPG) (β -5.12 mg/dL; 95% CI, -8.09, -2.16; p=.001), serum insulin levels (β -1.49 µIU/mL; 95% CI, -2.28, -0.70; p<.001), homeostasis model of assessment-insulin resistance (β -0.36; 95% CI, -0.55, -0.17; p<.001), serum triglycerides (β 12.42 mg/dL; 95% CI, -20.47, -4.37; p=.003) and VLDL-cholesterol levels (β -2.48 mg/dL; 95% CI, -4.09, -0.87; p=.003), and significantly increased the quantitative insulin sensitivity check index (β 0.006; 95% CI, 0.002, 0.01; p=.006) compared with metformin. Moreover, myo-inositol supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (p=.002) compared with metformin. Overall, taking myo-inositol, compared with metformin, for 12 weeks by women with PCOS had beneficial effects on glycemic control, triglycerides and VLDL-cholesterol levels, and gene expression of PPAR-γ.
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10.
Triacylglycerol-Lowering Effect of Docosahexaenoic Acid Is Not Influenced by Single-Nucleotide Polymorphisms Involved in Lipid Metabolism in Humans.
AbuMweis, SS, Panchal, SK, Jones, PJH
Lipids. 2018;(9):897-908
Abstract
The triacylglycerol (TAG)-lowering effects of long-chain n-3 fatty acids, and in particular docosahexaenoic acid (DHA), are well documented, although these effects manifest large interindividual variability. The objective of this secondary analysis is to investigate whether common single-nucleotide polymorphisms (SNP) in genes involved in DHA synthesis and TAG metabolism are associated with the responsiveness of blood lipids, lipoprotein, and apolipoprotein concentration to dietary treatment by DHA supplied in high-oleic canola oil (HOCO). In a randomized, crossover-controlled feeding trial, 129 subjects with metabolic syndrome received high-oleic canola oil (HOCO) and high-oleic canola oil supplemented with DHA (HOCO-DHA), each for 4 weeks. During the HOCO-DHA phase, the intake of DHA ranged from 1 to 2.5 g/day. The subjects were genotyped for apolipoprotein E (APOE) isoforms, and SNP including FADS1-rs174561, FADS2-rs174583, ELOVL2-rs953413, ELOVL5-rs2397142, CETP-rs5882, SCD1-rs2234970, PPARA-rs6008259, and LIPF-rs814628 were selected as important genes controlling fatty acid metabolism. Overall, consumption of HOCO-DHA oil reduced blood concentrations of TAG by 24% compared to HOCO oil. The reduction in TAG was independent of genetic variations in the studied genes. Similarly, no treatment-by-gene interactions were evident in the response to other lipids, lipoproteins, or apolipoproteins to DHA supplementation. Nevertheless, a lower interindividual variation in the TAG response to DHA supplementation compared to other studies was observed in this analysis. The TAG-lowering effect of a supplemental body-weight-based dose of DHA was not influenced by genetic variations in APOE, FADS1, FADS2, ELOVL2, ELOVL5, CETP, SCD1, PPARA, and LIPF.