Cardiovascular and Metabolic Disease Center
Mitochondrial Research Affinity Collaboration-Laboratories & Engineering

Home > 0

Cholesterol implicated in progression of fatty liver disease

  • 작성자한진
  • 작성일2006-09-10 09:51:23
  • 조회수6099
  • 첨부파일첨부파일
Public release date: 5-Sep-2006 [ Print Article | E-mail Article | Close Window ] Contact: Heidi Hardman hhardman@cell.com 617-397-2879 Cell Press Cholesterol implicated in progression of fatty liver disease Cholesterol may play an important role in the progression of fatty liver to an advanced stage of disease that can lead to permanent liver damage, according to a report in the September, 2006 issue of the journal Cell Metabolism, published by Cell Press. The findings suggest that low-cholesterol diets or cholesterol-lowering drugs might offer a useful therapy for the rising epidemic of fatty liver disease. The researchers found in mice that accumulation of cholesterol in the liver depletes a powerful antioxidant. The depleted cells are left sensitive to inflammatory factors that cause damage to the liver, they found. The buildup of other forms of fat in the liver, including free fatty acids and triglycerides, were insufficient to spark the events leading to worsening disease. The findings suggest a key role for the type, as opposed to the amount, of fat in susceptibility to the liver condition known as nonalcoholic steatohepatitis (NASH), said Jos?Fernandez-Checa and Carmen Garc?-Ruiz of Consejo Superior de Investigaciones Cient?icas (CSIC) in Barcelona. "To avoid the progression of liver disease, it may be important to eat less and be more conscious of the lipid content of the diet, particularly cholesterol," Fernandez-Checa said. Supplements that boost levels of glutathione--the antioxidant that becomes depleted in animals whose livers accumulate cholesterol--might also be beneficial, he added. "These data also support a potential therapeutic role of statins in NASH development," he added. Statins are a class of drugs used to lower cholesterol in those at risk of cardiovascular disease. Characterized by fat accumulation, inflammation, and liver damage, NASH affects 2%?% percent of Americans. An additional 10%?0% percent of Americans have fat in their liver, but no inflammation or liver damage. Both conditions are becoming more prevalent, possibly due to the rise of obesity. The accumulation of lipids in the liver cells, mostly in the form of fatty acids and triglycerides, had been considered the first step in the development of fatty liver disease, the researchers said. However, disease progression usually does not occur in the absence of a second hit that promotes oxidative stress, inflammation, cell death, and fibrosis. In the current study, the researchers examined the connection between fat type and liver disease progression in mice with high levels of particular lipids in the liver as a result of their diet or genetic modifications that left them obese or unable to handle cholesterol properly. In every case, mice with high levels of cholesterol in their livers became increasingly susceptible to two inflammatory factors known as cytokines, they found. The cholesterol accumulated specifically in the cellular powerhouses known as mitochondria, where it caused a drop in glutathione. Treatments that selectively depleted liver cells of glutathione produced symptoms that mirrored the effects of high liver cholesterol, they reported. In obese mice, treatment with the cholesterol-lowering drug Atorvastatin prevented the cholesterol increase in mitochondria and restored antioxidant levels, offering protection from liver damage. The new findings represent some of the first evidence for a role of cholesterol in delivering the "second hit" that leads to full-blown NASH, Fernandez-Checa said. Earlier studies that found a poor correlation between blood cholesterol levels and fatty liver disease had led to some doubt about cholesterol's role, he added. Cholesterol metabolism is a complicated process, however, such that blood levels might not always reflect the amount of cholesterol in the liver, he said. ### The researchers include Montserrat Mar? Francisco Caballero, Anna Colell, Albert Morales, Juan Caballeria, Anna Fernandez, Carlos Enrich, Jos?C. Fernandez-Checa, and Carmen Garc?-Ruiz of the Universitat de Barcelona, Instituto Investigaciones Biom?icas August Pi i Sunyer (IDIBAPS), Consejo Superior de Investigaciones Cient?icas in Barcelona, Spain. The work presented was supported in part by the Research Center for Liver and Pancreatic Diseases, P50 AA 11999; and grant 1R21 AA014135-01, funded by the US National Institute on Alcohol Abuse and Alcoholism; Plan Nacional de I+D grants SAF (2002-3564, 2003-04974, 2005-03923, 2005-03943); and Red Tem?ica de Investigaci? Cooperativa G03/015, Red de Centros C03/02 and FIS (04/1039, 03/0426, 02/3057 and 02/0339) grants supported by Instituto de Salud Carlos III, Spain. Mar?et al.: "Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis." Publishing in Cell Metabolism 4, 185?98, September 2006 DOI 10.1016/j.cmet.2006.07.006 www.cellmetabolism.org Related Preview by Ginsberg et al.: "Is the slippery slope from steatosis to steatohepatitis paved with triglyceride or cholesterol?"
Total405 [ page3/27 ]
No. 제목 작성자 작성일 조회수
375 Error bars in experimental biology 첨부파일 2011.05.02 허혜진 2011.05.02 3,128
374 파킨슨 질병은 미토콘드리아 complex 1 손상 보다 microtuble 에 의해서 생길수도... 라는 논문 2011.03.08 김형규 2011.03.08 5,383
373 운동을 안해도,운동한 것처럼 건강한 심장을 만들어 주는 유전자 2011.01.06 서대윤 2011.01.06 3,899
372 2010 ㅡmitophysiology conference, Young Investigator Award 수상 2010.11.16 김형규 2010.11.16 3,353
371 3차원 세포의 세계 2010.10.27 김민희 2010.10.27 2,641
370 인제대 '심혈관.대사질환센터' 중점연구소 선정 -연합뉴스 2010.08.10 김형규 2010.08.10 4,078
369 7월 연구노트 작성 우수상 시상 2010.08.03 김민희 2010.08.03 2,992
368 NYAS 리뷰 논문 게재 - 김형규,하승희 2010.08.02 김형규 2010.08.02 3,723
367 박원선 교수님과 최일환 교수님의 논문이 publish 되었습니다. 2010.07.09 최성우 2010.07.09 4,350
366 김형규-부티투 4회 미토콘드리아 연구의학회 best research award 수상 첨부파일 2010.07.06 김형규 2010.07.06 2,189
365 6월 연구노트 작성 우수상 시상 2010.06.28 최성우 2010.06.28 2,544
364 4th Conference of Korean Society for Mitochondrial Reaserch and Medicine 첨부파일 2010.06.17 최성우 2010.06.17 3,672
363 5월 연구노트 작성 우수상 시상 2010.05.31 최성우 2010.05.31 3,002
362 안준석 - 제18회 기초의학 학술대회,학생논문발표대회 최우수상 수상 첨부파일 2010.05.28 최성우 2010.05.28 3,377
361 제 6회 논문연구계획서 발표대회: 최성우 학생 우수상 수상 첨부파일 2010.04.28 최성우 2010.04.28 2,859
처음이전 1 2 3 4 5 6 7 8 9 10 다음 마지막