57
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Lipid droplets and liver disease: from basic biology to clinical implications

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Lipid droplets are dynamic organelles that store neutral lipids during times of energy excess and serve as an energy reservoir during deprivation. Many prevalent metabolic diseases, such as the metabolic syndrome or obesity, often result in abnormal lipid accumulation in lipid droplets in the liver, also called hepatic steatosis. Obesity-related steatosis, or NAFLD in particular, is a major public health concern worldwide and is frequently associated with insulin resistance and type 2 diabetes mellitus. Here, we review the latest insights into the biology of lipid droplets and their role in maintaining lipid homeostasis in the liver. We also offer a perspective of liver diseases that feature lipid accumulation in these lipid storage organelles, which include NAFLD and viral hepatitis. Although clinical applications of this knowledge are just beginning, we highlight new opportunities for identifying molecular targets for treating hepatic steatosis and steatohepatitis.

          Related collections

          Most cited references190

          • Record: found
          • Abstract: found
          • Article: not found

          Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

          In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

            Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9×10−10) and with hepatic inflammation (P=3.7×10−4). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found

              The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD).

              Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis.
                Bookmark

                Author and article information

                Journal
                101500079
                35771
                Nat Rev Gastroenterol Hepatol
                Nat Rev Gastroenterol Hepatol
                Nature reviews. Gastroenterology & hepatology
                1759-5045
                1759-5053
                24 October 2018
                21 April 2017
                June 2017
                04 January 2019
                : 14
                : 6
                : 343-355
                Affiliations
                [1 ]Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, USA.
                [2 ]Boston Children’s Hospital Department of Gastroenterology, Hepatology and Nutrition, 300 Longwood Avenue Boston, Massachusetts 02115, USA.
                [3 ]Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue Boston, Massachusetts 02115, USA.
                [4 ]Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur Boston, Massachusetts 02115, USA.
                [5 ]Howard Hughes Medical Institute, Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, USA.
                Author notes
                Correspondence to T.C.W. and R.V.F., Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, USA., robert@ 123456hsph.harvard.edu ;, twalther@ 123456hsph.harvard.edu

                Author contributions

                All authors contributed to the research, discussion, writing and reviewing/editing of the manuscript before submission.

                Article
                PMC6319657 PMC6319657 6319657 nihpa994067
                10.1038/nrgastro.2017.32
                6319657
                28428634
                958fac90-b1e6-47e5-8f55-d417b3f4d0f4
                History
                Categories
                Article

                Comments

                Comment on this article