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

被引:478
作者
Gluchowski, Nina L. [1 ,2 ]
Becuwe, Michel [1 ]
Walther, Tobias C. [1 ,3 ,4 ,5 ]
Farese, Robert V., Jr. [1 ,3 ,4 ]
机构
[1] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, 655 Huntington Ave, Boston, MA 02115 USA
[2] Boston Childrens Hosp, Dept Gastroenterol Hepatol & Nutr, 300 Longwood Ave, Boston, MA 02115 USA
[3] Harvard Med Sch, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA
[4] Harvard Med Sch, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA
[5] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Howard Hughes Med Inst, 655 Huntington Ave, Boston, MA 02115 USA
关键词
HEPATITIS-C VIRUS; ADIPOSE TRIGLYCERIDE LIPASE; DIACYLGLYCEROL ACYLTRANSFERASE 1; HORMONE-SENSITIVE LIPASE; COA-CHOLESTEROL ACYLTRANSFERASE; ENDOPLASMIC-RETICULUM STRESS; INDUCED INSULIN-RESISTANCE; LOW-DENSITY LIPOPROTEINS; GENOME-WIDE ASSOCIATION; FATTY-ACID TRAFFICKING;
D O I
10.1038/nrgastro.2017.32
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:343 / 355
页数:13
相关论文
共 202 条
  • [1] Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity
    Adinolfi, LE
    Gambardella, M
    Andreana, A
    Tripodi, MF
    Utili, R
    Ruggiero, G
    [J]. HEPATOLOGY, 2001, 33 (06) : 1358 - 1364
  • [2] SUBCELLULAR-LOCALIZATION OF B APOPROTEIN OF PLASMA LIPOPROTEINS IN RAT-LIVER
    ALEXANDER, CA
    HAMILTON, RL
    HAVEL, RJ
    [J]. JOURNAL OF CELL BIOLOGY, 1976, 69 (02) : 241 - 263
  • [3] ALTMAN R., 1890, ELEMENTARORGANISMEN
  • [4] Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates
    Anderson, RA
    Joyce, C
    Davis, M
    Reagan, JW
    Clark, M
    Shelness, GS
    Rudel, LL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) : 26747 - 26754
  • [5] Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease
    Angulo, Paul
    Kleiner, David E.
    Dam-Larsen, Sanne
    Adams, Leon A.
    Bjornsson, Einar S.
    Charatcharoenwitthaya, Phunchai
    Mills, Peter R.
    Keach, Jill C.
    Lafferty, Heather D.
    Stahler, Alisha
    Haflidadottir, Svanhildur
    Bendtsen, Flemming
    [J]. GASTROENTEROLOGY, 2015, 149 (02) : 389 - +
  • [6] POSSIBLE ROLE OF THE GOLGI-APPARATUS IN THE ASSEMBLY OF VERY LOW-DENSITY-LIPOPROTEIN
    BAMBERGER, MJ
    LANE, MD
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (07) : 2390 - 2394
  • [7] Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic
    Bartz, Rene
    Li, Wen-Hong
    Venables, Barney
    Zehmer, John K.
    Roth, Mary R.
    Welti, Ruth
    Anderson, Richard G. W.
    Liu, Pingsheng
    Chapman, Kent D.
    [J]. JOURNAL OF LIPID RESEARCH, 2007, 48 (04) : 837 - 847
  • [8] Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome
    Basantani, Mahesh K.
    Sitnick, Mitch T.
    Cai, Lingzhi
    Brenner, Daniel S.
    Gardner, Noah P.
    Li, John Zhong
    Schoiswohl, Gabriele
    Yang, Kui
    Kumari, Manju
    Gross, Richard W.
    Zechner, Rudolf
    Kershaw, Erin E.
    [J]. JOURNAL OF LIPID RESEARCH, 2011, 52 (02) : 318 - 329
  • [9] COPI Complex Is a Regulator of Lipid Homeostasis
    Beller, Mathias
    Sztalryd, Carole
    Southall, Noel
    Bell, Ming
    Jaeckle, Herbert
    Auld, Douglas S.
    Oliver, Brian
    [J]. PLOS BIOLOGY, 2008, 6 (11) : 2530 - 2549
  • [10] BLANCHETTEMACKIE EJ, 1983, J LIPID RES, V24, P229