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Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments.
Kitade, H, Chen, G, Ni, Y, Ota, T
Nutrients. 2017;(4)
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood. Both innate and recruited immune cells mediate the development of insulin resistance and NASH. Therefore, modifying the polarization of resident and recruited macrophage/Kupffer cells is expected to lead to new therapeutic strategies in NAFLD. Oxidative stress is also pivotal for the progression of NASH, which has generated interest in carotenoids as potent micronutrient antioxidants in the treatment of NAFLD. In addition to their antioxidative function, carotenoids regulate macrophage/Kupffer cell polarization and thereby prevent NASH progression. In this review, we summarize the molecular mechanisms involved in the pathogenesis of NAFLD, including macrophage/Kupffer cell polarization, and disturbed hepatic function in NAFLD. We also discuss dietary antioxidants, such as β-cryptoxanthin and astaxanthin, that may be effective in the prevention or treatment of NAFLD.
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Effects of simvastatin on carotenoid status in plasma.
Rydén, M, Leanderson, P, Kastbom, KO, Jonasson, L
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2012;(1):66-71
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Abstract
BACKGROUND AND AIMS Carotenoids are potent antioxidants mainly transported in the low density lipoprotein (LDL) fraction. They may also influence the immune response and inverse associations with inflammatory markers have been reported. We investigated whether simvastatin, by exerting both lipid-lowering and anti-inflammatory effects, altered the carotenoid status in plasma. METHODS AND RESULTS A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. Lipids, oxidized LDL (ox-LDL), C-reactive protein (CRP), interleukin (IL)-6, oxygenated carotenoids (lutein, zeaxanthin, β-cryptoxanthin) and hydrocarbon carotenoids (α-carotene, β-carotene, lycopene) were measured in plasma. Simvastatin use was associated with significant reductions in total cholesterol, LDL, ox-LDL and CRP. Simvastatin therapy also resulted in reduced plasma levels of both oxygenated and hydrocarbon carotenoids. However, when adjusted for lipids, all carotenoids except β-cryptoxanthin showed significant increases after simvastatin therapy. Both crude and lipid-adjusted carotenoids were inversely correlated with CRP and IL-6 in plasma but the change in carotenoid status during simvastatin therapy was not specifically related to any changes in inflammatory markers. CONCLUSIONS To summarize, the change in carotenoid status during simvastatin therapy was mainly attributed to the lowering of cholesterol and not to the suppression of inflammatory activity. After adjustment for lipids, the levels of lutein, lycopene, α-carotene and β-carotene were significantly increased by simvastatin suggesting an increased ratio of carotenoids per particle.
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In vitro screening of relative bioaccessibility of carotenoids from foods.
Failla, ML, Huo, T, Thakkar, SK
Asia Pacific journal of clinical nutrition. 2008;:200-3
Abstract
Carotenoids are lipophilic pigments in plant foods that are of particular interest as precursors of vitamin A, a nutrient required for vision, cell differentiation, and the immune system. In order to mediate such activities, carotenoids and their metabolites must be absorbed for delivery to tissues. Unlike many other dietary lipids, the efficiency of carotenoid absorption is typically inefficient, being affected by food matrix, style of processing, other dietary components, and nutritional and physiological status. Thus, reliable prediction of carotenoid bioavailability is problematic. We have developed a relatively simple and cost effective procedure to study the potential bioavailability, i.e., the bioaccessibility, of carotenoids. The method involves simulated oral, gastric and small intestinal digestion of test samples to access the efficiency of incorporation into micelles, an obligatory step for absorption of lipophilic compounds. The model can be further expanded by adding micelles generated during small intestinal phase of digestion to monolayers of Caco-2 human intestinal epithelial cells to investigate apical uptake, cellular metabolism and transepithelial transport of carotenoids. Recent work by Borel and associates has demonstrated that the relative bioaccessibility of carotenoids observed in vitro is highly correlated with in vivo observations and results from bioavailability trials with human subjects. Results from recent studies using the in vitro model to screen relative bioaccessibility of beta-carotene in various cultivars of cassava, impact of amount and types of fatty acyl groups in triglycerides on micellarization of carotenoids, and the mechanism of digestion and intestinal cell uptake of xanthophyll esters are presented.
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Plasma carotenoid concentrations in relation to acute respiratory infections in elderly people.
van der Horst-Graat, JM, Kok, FJ, Schouten, EG
The British journal of nutrition. 2004;(1):113-8
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Abstract
A high plasma carotenoid concentration could improve the immune response and result in decreased risk of infectious diseases. However, data on the relationship of plasma carotenoid concentration with acute respiratory infections, which occur frequently in elderly people, are scarce. We investigated, therefore, the relationship of plasma concentrations of six major carotenoids (beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin) with the incidence and severity of acute respiratory infections. Baseline data from an intervention trial were used. Participants were 652 non-institutionalized elderly people (> or =60 years old) enrolled via two community-based sampling strategies in the Wageningen area of The Netherlands in 1998-99. Plasma carotenoid concentrations were divided into quartiles, the lowest being the reference. Frequency and severity of episodes during the previous 1 year, i.e. staying in bed, medical consultation and episode-related medication, were self-reported by means of a questionnaire. On average 1.6 episodes per person were recorded. The incidence rate ratio of acute respiratory infections at high beta-carotene status was 0.71 (95 % CI 0.54-0.92) as compared with the low beta-carotene concentration group. No association was observed between beta-carotene and illness severity. alpha-Carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin were not related to incidence or severity of the infections. We conclude that elderly people with a high plasma beta-carotene concentration may have a lower occurrence of acute respiratory infections.