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      Sake lees extract improves hepatic lipid accumulation in high fat diet-fed mice

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          Abstract

          Background

          Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide as one of the leading causes of chronic liver disease. Sake lees (SL) are secondary products of sake manufacturing and are considered to have beneficial effects on human health. To investigate these effects, we used high fat diet (HFD)-fed mice treated with or without the SL extract.

          Method

          Mice were the HFD ad libitum for 8 weeks and were administered 500 μL of distilled water with or without the SL extract (350 mg/mL) by a feeding needle daily for the last 4 weeks. Food intake, body weight, and liver weight were measured. Triacylglycerol content and the mRNA and protein expression levels of various lipid and glucose metabolism-related genes were determined in liver tissues. The levels of triglyceride, free fatty acids, glucose, insulin, and liver cell damage markers were determined in serum. Fatty acid-induced lipid accumulation in HepG2 cells was assessed in the presence or absence of the SL extract.

          Results

          Mice fed a HFD and treated with the SL extract demonstrated a significant reduction in hepatic lipid accumulation and mRNA and protein levels of peroxidome proliferator-activated receptor γ (PPARγ), PPARα, CD36, and phosphoenolpyruvate carboxykinase 1 in the liver, while the SL extract did not affect body weight and food intake. Moreover, insulin resistance and hepatic inflammation in HFD-fed mice improved after administration of the SL extract. In HepG2 cells, the SL extract suppressed fatty acid-induced intracellular lipid accumulation.

          Conclusions

          These findings suggest that treatment with the SL extract could potentially reduce the risk of NAFLD development, and that the SL extract may be clinically useful for the treatment of NAFLD.

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          Most cited references19

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          Nonalcoholic fatty liver disease: pathology and pathogenesis.

          Nonalcoholic fatty liver disease (NAFLD) is recognized as the leading cause of chronic liver disease in adults and children. NAFLD encompasses a spectrum of liver injuries ranging from steatosis to steatohepatitis with or without fibrosis. Fibrosis may progress to cirrhosis and complications including hepatocellular carcinoma. Histologic findings represent the complexity of pathophysiology. NAFLD is closely associated with obesity and is most closely linked with insulin resistance; the current Western diet, high in saturated fats and fructose, plays a significant role. There are several mechanisms by which excess triglycerides are acquired and accumulate in hepatocytes. Formation of steatotic droplets may be disordered in NAFLD. Visceral adipose tissue dysfunction in obesity and insulin resistance results in aberrant cytokine expression; many cytokines have a role in liver injury in NAFLD. Cellular stress and immune reactions, as well as the endocannabinoid system, have been implicated in animal models and in some human studies.
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            Pathology of nonalcoholic fatty liver disease.

            Nonalcoholic fatty liver disease (NAFLD) is a significant complication of obesity and is recognized as the hepatic manifestation of the metabolic syndrome. The process occurs in adults and children and is characterized by the presence of increased amounts of fat in the liver (steatosis). With inflammation, cell death and scarring (fibrosis), the process may result in end-stage liver disease, or be a precursor for hepatocellular carcinoma. Excess hepatic fat is now recognized as an independent marker for increased cardiovascular risk. Even though imaging studies and laboratory-based tests are accurate at detecting significant steatosis and/or advanced fibrosis, respectively, the diagnosis and characterization of NAFLD ultimately depend on histopathologic evaluation, as the parenchymal alterations that comprise the spectrum of injury in NAFLD include patterns as well as specific lesions. Histologic findings in children may differ from those in adults. In this Review, the histologic features that are diagnostic and discriminatory between steatosis and steatohepatitis, the significance of the distinction between steatosis and steatohepatitis, the types and locations of fibrosis, and the histologic variances between adult and pediatric NAFLD are discussed. Clinical advantages as well as potential drawbacks of liver biopsy are presented. Current pathophysiologic concepts relevant to histologic findings are discussed.
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              A systematic review and meta-analysis on the effects of exercise training versus hypocaloric diet: distinct effects on body weight and visceral adipose tissue.

              Exercise training ('exercise') and hypocaloric diet ('diet') are frequently prescribed for weight loss in obesity. Whilst body weight changes are commonly used to evaluate lifestyle interventions, visceral adiposity (VAT) is a more relevant and stronger predictor for morbidity and mortality. A meta-analysis was performed to assess the effects of exercise or diet on VAT (quantified by radiographic imaging). Relevant databases were searched through May 2014. One hundred seventeen studies (n = 4,815) were included. We found that both exercise and diet cause VAT loss (P < 0.0001). When comparing diet versus training, diet caused a larger weight loss (P = 0.04). In contrast, a trend was observed towards a larger VAT decrease in exercise (P = 0.08). Changes in weight and VAT showed a strong correlation after diet (R(2)  = 0.737, P < 0.001), and a modest correlation after exercise (R(2)  = 0.451, P < 0.001). In the absence of weight loss, exercise is related to 6.1% decrease in VAT, whilst diet showed virtually no change (1.1%). In conclusion, both exercise and diet reduce VAT. Despite a larger effect of diet on total body weight loss, exercise tends to have superior effects in reducing VAT. Finally, total body weight loss does not necessarily reflect changes in VAT and may represent a poor marker when evaluating benefits of lifestyle-interventions.
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                Author and article information

                Contributors
                kubo.hisako.82r@st.kyoto-u.ac.jp
                mhoshi@fujita-hu.ac.jp
                matsumoto.takuya@st.kyoto-u.ac.jp
                irie@gekkeikan.co.jp
                oura@gekkeikan.co.jp
                h_tsutsumi@gekkeikan.co.jp
                y_hata@gekkeikan.co.jp
                yama-y@fujita-hu.ac.jp
                +81-562-93-2611 , saitok@fujita-hu.ac.jp
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                3 June 2017
                3 June 2017
                2017
                : 16
                : 106
                Affiliations
                [1 ]ISNI 0000 0004 0372 2033, GRID grid.258799.8, Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, , Kyoto University, ; 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507 Japan
                [2 ]ISNI 0000 0004 1761 798X, GRID grid.256115.4, Department of Biochemical and Analytical Sciences, , Fujita Health University Graduate School of Health Sciences, ; 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan
                [3 ]ISNI 0000 0004 0377 2137, GRID grid.416629.e, , Research Institute, Gekkeikan Sake Co. Ltd., ; 247 Minamihamcho, Fushimi, Kyoto, 612-8385 Japan
                [4 ]ISNI 0000 0004 1761 798X, GRID grid.256115.4, Department of Disease Control and Prevention, , Fujita Health University Graduate School of Health Sciences, ; 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192 Japan
                Article
                501
                10.1186/s12944-017-0501-y
                5457550
                159ada4a-eb00-4057-9595-4811ba801ffe
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 December 2016
                : 25 May 2017
                Funding
                Funded by: Gekkeikan Sake Co., Ltd
                Award ID: 2016
                Award Recipient :
                Funded by: Fujita Health University grant
                Award ID: 2016
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Biochemistry
                sake lees extract,nafld,lipid accumulation,insulin resistance
                Biochemistry
                sake lees extract, nafld, lipid accumulation, insulin resistance

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