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      Dietary fiber prevents obesity-related liver lipotoxicity by modulating sterol-regulatory element binding protein pathway in C57BL/6J mice fed a high-fat/cholesterol diet

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          Abstract

          Adequate intake of dietary fibers has proven metabolic and cardiovascular benefits, molecular mechanisms remain still limited. This study was aimed to investigate the effects of cereal dietary fiber on obesity-related liver lipotoxicity in C57BL/6J mice fed a high-fat/cholesterol (HFC) diet and underlying mechanism. Forty-eight adult male C57BL/6J mice were randomly given a reference chow diet, or a high fat/choleserol (HFC) diet supplemented with or without oat fiber or wheat bran fiber for 24 weeks. Our results showed mice fed oat or wheat bran fiber exhibtied lower weight gain, lipid profiles and insulin resistance, compared with HFC diet. The two cereal dietary fibers potently decreased protein expressions of sterol regulatory element binding protein-1 and key factors involved in lipogenesis, including fatty acid synthase and acetyl-CoA carboxylase in target tissues. At molecular level, the two cereal dietary fibers augmented protein expressions of peroxisome proliferator-activated receptor alpha and gamma, liver X receptor alpha, and ATP-binding cassette transporter A1 in target tissues. Our findings indicated that cereal dietary fiber supplementation abrogated obesity-related liver lipotoxicity and dyslipidemia in C57BL/6J mice fed a HFC diet. In addition, the efficacy of oat fiber is greater than wheat bran fiber in normalizing these metabolic disorders and pathological profiles.

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          Most cited references29

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          Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta.

          The liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that are bound and activated by oxysterols. These receptors serve as sterol sensors to regulate the transcription of gene products that control intracellular cholesterol homeostasis through catabolism and transport. In this report, we describe a novel LXR target, the sterol regulatory element-binding protein-1c gene (SREBP-1c), which encodes a membrane-bound transcription factor of the basic helix-loop-helix-leucine zipper family. SREBP-1c expression was markedly increased in mouse tissues in an LXR-dependent manner by dietary cholesterol and synthetic agonists for both LXR and its heterodimer partner, the retinoid X receptor (RXR). Expression of the related gene products, SREBP-1a and SREBP-2, were not increased. Analysis of the mouse SREBP-1c gene promoter revealed an RXR/LXR DNA-binding site that is essential for this regulation. The transcriptional increase in SREBP-1c mRNA by RXR/LXR was accompanied by a similar increase in the level of the nuclear, active form of the SREBP-1c protein and an increase in fatty acid synthesis. Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis, our results reveal a unique regulatory interplay between cholesterol and fatty acid metabolism.
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            Dietary fiber and body weight.

            This review provides an update of recent studies of dietary fiber and weight and includes a discussion of potential mechanisms of how dietary fiber can aid weight loss and weight maintenance. Human studies published on dietary fiber and body weight were reviewed and summarized. Dietary fiber content of popular low-carbohydrate diets were calculated and are presented. Epidemiologic support that dietary fiber intake prevents obesity is strong. Fiber intake is inversely associated with body weight and body fat. In addition, fiber intake is inversely associated with body mass index at all levels of fat intake after adjusting for confounding factors. Results from intervention studies are more mixed, although the addition of dietary fiber generally decreases food intake and, hence, body weight. Many mechanisms have been suggested for how dietary fiber aids in weight management, including promoting satiation, decreasing absorption of macronutrients, and altering secretion of gut hormones. The average fiber intake of adults in the United States is less than half recommended levels and is lower still among those who follow currently popular low-carbohydrate diets, such as Atkins and South Beach. Increasing consumption of dietary fiber with fruits, vegetables, whole grains, and legumes across the life cycle is a critical step in stemming the epidemic of obesity found in developed countries. The addition of functional fiber to weight-loss diets should also be considered as a tool to improve success.
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              Integrated physiology and systems biology of PPARα

              The Peroxisome Proliferator Activated Receptor alpha (PPARα) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARα, with a focus on liver. A distinction is made between the impact of PPARα on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARα as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARα at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARα governs the expression of several secreted proteins that exert local and endocrine functions.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                29 October 2015
                2015
                : 5
                : 15256
                Affiliations
                [1 ]Department of Nutrition and Food Hygiene, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University , 199 Renai Road, Suzhou City 215123, China
                [2 ]Key Laboratory of Radiation Biology, School of Radiation Medicine and Protection, Soochow University , 199 Renai Road, Suzhou City 215123, China
                [3 ]DSM Nutritional Products Human Nutrition and Health , Unite 5-7, Floor 8, Tower C, Parkview Green, 9 Dongdaqiao Road, Beijing 100020, China
                [4 ]DSM Nutritional Products Human Nutrition and Health , 476 Libing Road, Shanghai 201203, China
                Author notes
                Article
                srep15256
                10.1038/srep15256
                4625144
                26510459
                0b5e6a23-9f13-4c00-aa76-97ef63a3262d
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 11 January 2015
                : 16 September 2015
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