Abstract：
:Lysosomal acid lipase (LAL) is essential for the hydrolysis of triglycerides (TG) and cholesteryl esters (CE) in lysosomes. A mouse model created by gene targeting produces no LAL mRNA, protein, or enzyme activity. The lal-/- mice appear normal at birth, survive into adulthood, and are fertile. Massive storage of TG and CE is observed in adult liver, adrenal glands, and small intestine. The age-dependent tissue and gross progression in this mouse model are detailed here. Although lal-/- mice can be bred to give homozygous litters, they die at ages of 7 to 8 months. The lal-/- mice develop enlargement of a single mesenteric lymph node that is full of stored lipids. At 6;-8 months of age, the lal-/- mice have completely absent inguinal, interscapular, and retroperitoneal white adipose tissue. In addition, brown adipose tissue is progressively lost. The plasma free fatty acid levels are significantly higher in lal-/- mice than age-matched lal+/+ mice, and plasma insulin levels were more elevated upon glucose challenge. Energy intake was also higher in lal-/- male mice, although age-matched body weights were not significantly altered from age-matched lal+/+ mice. Early in the disease course, hepatocytes are the main storage cell in the liver; by 3;-8 months, the lipid-stored Kupffer cells progressively fill the liver. The involvement of macrophages throughout the body of lal-/- mice provide evidence for a critical nonappreciated role of LAL in cellular cholesterol and fatty acid metabolism, adipocyte differentiation, and fat mobilization.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Du H,Heur M,Duanmu M,Grabowski GA,Hui DY,Witte DP,Mishra Jkeywords:
subject
Has Abstractpub_date
2001-04-01 00:00:00pages
489-500issue
4eissn
0022-2275issn
1539-7262journal_volume
42pub_type
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M013235
更新日期：2011-08-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
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更新日期：2010-06-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-09-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D087429
更新日期：2018-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400130-JLR200
更新日期：2004-08-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-04-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400425-JLR200
更新日期：2005-06-01 00:00:00
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doi：10.1194/jlr.M400444-JLR200
更新日期：2005-04-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-09-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1970-09-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:Cholesterol 7α-hydroxylase (CYP7A1) is the first and rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In addition to absorption and digestion of nutrients, bile acids play a critical role in the regulation of lipid, glucose, and energy homeostasis. We have backcrossed Cyp7a1(-/-) mice ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M064709
更新日期：2016-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100433-jlr200
更新日期：2002-10-01 00:00:00
abstract：:The initial studies of the metabolism of arachidonic acid (AA) by the cytochrome P450 (P450) hemeproteins sought to: a) elucidate the roles for these enzymes in the metabolism of endogenous pools of the FA, b) identify the P450 isoforms involved in AA epoxidation and ω/ω-1 hydroxylation, and c) explore the biological ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.R087882
更新日期：2018-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA119000256
更新日期：2020-01-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:To determine the acute effects of insulin on lipoprotein metabolism, we have followed the plasma lipoprotein lipid and apolipoprotein levels during insulin therapy for the first 24 hr in 13 patients with diabetic ketoacidosis. Corrections were made for plasma volume changes during treatment. Before insulin treatment, ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-01-01 00:00:00
abstract：:Imidazole catalyzed acylations of lysolipids by acyl-CoAs in water at room temperature and at a pH close to neutrality. In the presence of oleoyl-CoA and either lysophosphatidylcholine, 1-palmitoyl-sn-glycero-3-phosphocholine (LPC); lysophosphatidylglycerol, monoacyl-sn-glycero-3-phosphoglycerol; lysophosphatidyl acid...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200075-jlr200
更新日期：2002-07-01 00:00:00
abstract：:Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to aff...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100254-jlr200
更新日期：2002-07-01 00:00:00
abstract：:The recent insight that inflammation contributes to the development of atherosclerosis and type 2 diabetes mellitus constitutes a major breakthrough in understanding the mechanisms underlying these conditions. In addition, it opens the way for new therapeutic approaches that might eventually decrease the prevalence of...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R600021-JLR200
更新日期：2007-04-01 00:00:00
abstract：:The bile acid (BA) composition in mice is substantially different from that in humans. Chenodeoxycholic acid (CDCA) is an end product in the human liver; however, mouse Cyp2c70 metabolizes CDCA to hydrophilic muricholic acids (MCAs). Moreover, in humans, the gut microbiota converts the primary BAs, cholic acid and CDC...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.RA119000395
更新日期：2020-01-01 00:00:00
abstract：:Bovine aortic endothelial cells take up 12-hydroxyeicosatetraenoic acid (12-HETE), a lipoxygenase product formed from arachidonic acid. The uptake of [3H]12-HETE reached a maximum in 2 to 4 h. At this time, from 75 to 80% of the incorporated radioactivity was contained in phospholipids, about 85% of the esterified rad...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:The alpha-naphthylisothiocyanate (ANIT)-treated rat was evaluated as a model for lipoprotein metabolism in cholestatic liver disease. Alterations in lipoprotein composition over a period of 120 h after ANIT treatment (100 mg/kg) were studied. Eighteen hours after treatment, plasma bilirubin and bile acid levels began ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:Elevated serum levels of triglyceride-rich remnant lipoproteins (TRL) are a major risk factor predisposing a subject to atherosclerosis. Apolipoprotein C-III (apoC-III) is a major constituent of TRL that impedes triglyceride hydrolysis and remnant clearance and, as such, may exert pro-atherogenic activities. In the pr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200386-jlr200
更新日期：2002-12-01 00:00:00
abstract：:Acetyl-L-carnitine is known as a reservoir of activated acetyl units and as a modulator of metabolic function. The objective of this study was to quantify the fate of the acetyl moiety of acetyl-L-carnitine in lipogenic pathways. Lipogenesis was studied in an adipocyte model, differentiated 3T3-L1 cells, and a hepatom...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-07-01 00:00:00
abstract：:HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1194/jlr.M400052-JLR200
更新日期：2005-03-01 00:00:00
abstract：:In addition to their classical roles as detergents to aid in the process of digestion, bile acids have been identified as important signaling molecules that function through various nuclear and G protein-coupled receptors to regulate a myriad of cellular and molecular functions across both metabolic and nonmetabolic p...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R054114
更新日期：2015-06-01 00:00:00
abstract：:Elongation of very long chain fatty acid-like family member 6 (ELOVL6) is a fatty acyl elongase that performs the initial and rate-limiting condensing reaction required for microsomal elongation of long-chain fatty acids. Our previous in vitro studies suggested that ELOVL6 elongated long-chain saturated fatty acids an...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054353
更新日期：2014-12-01 00:00:00
abstract：:A variety of methods are currently used to analyze HL and LPL activities in mice. In search of a simple methodology, we analyzed mouse preheparin and postheparin plasma LPL and HL activities using specific polyclonal antibodies raised in rabbit against rat HL (anti-HL) and in goat against rat LPL (anti-LPL). As an alt...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D700021-JLR200
更新日期：2007-12-01 00:00:00
