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 in a mixed B6/129Sv genetic background to C57BL/6J mice to generate Cyp7a1(-/-) mice in a near-pure C57BL/6J background. These mice survive well and have normal growth and a bile acid pool size ∼60% of WT mice. The expression of the genes in the alternative bile acid synthesis pathway are upregulated, resulting in a more hydrophilic bile acid composition with reduced cholic acid (CA). Surprisingly, Cyp7a1(-/-) mice have improved glucose sensitivity with reduced liver triglycerides and fecal bile acid excretion, but increased fecal fatty acid excretion and respiratory exchange ratio (RER) when fed a high-fat/high-cholesterol diet. Supplementing chow and Western diets with CA restored bile acid composition, reversed the glucose tolerant phenotype, and reduced the RER. Our current study points to a critical role of bile acid composition, rather than bile acid pool size, in regulation of glucose, lipid, and energy metabolism to improve glucose and insulin tolerance, maintain metabolic homeostasis, and prevent high-fat diet-induced metabolic disorders.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Ferrell JM,Boehme S,Li F,Chiang JYdoi
10.1194/jlr.M064709subject
Has Abstractpub_date
2016-07-01 00:00:00pages
1144-54issue
7eissn
0022-2275issn
1539-7262pii
jlr.M064709journal_volume
57pub_type
杂志文章abstract：:In an effort tao simulate the effects of insulin on fat cells prepared from fresh adipose tissue, pieces of epididymal adipose tissue were cultured in a medium containing charcoal-treated bovine serum albumin (BSA) with a gas phase of 100% O2. Using this system, the insulin effect on [1-14C]glucose oxidation was retai...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-02-01 00:00:00
abstract：:The conversion of alpha-linolenate (18:3n-3) to docosahexaenoate (22:6n-3) in the presence of low and high dietary levels of linoleate (18:2n-6) is reported in young rats using [U-13C]-alpha-linolenic acid (18:2n-3*) and high precision gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS). After con...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
abstract：:Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage disorder characterized by neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration. The present study provides the lipid profiles, mutations, and corresponding associations with the biochemical phenotype obtained from NPC1 ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P000331
更新日期：2010-02-01 00:00:00
abstract：:A three-step procedure has been developed for the separation of complex mixtures of sterol intermediates in cholesterol biosynthesis. The method has been applied to the separation of sterol intermediates formed from [14C]mevalonate by normal rat hepatocyte culture cells. In Step 1, a short gravity-flow silicic acid co...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：:Apolipoprotein (apo)A-IV is synthesized in the small intestine during fat absorption and is incorporated onto the surface of nascent chylomicrons. In circulation, apoA-IV is displaced from the chylomicron surface by high density lipoprotein-associated C and E apolipoproteins; this exchange is critical for activation o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
abstract：:Using [13C]-tracers and direct fetal doses, we show for the first time that the fetal primate converts alpha-linolenic acid (18:3) to docosahexaenoic acid (22:6) in vivo, and we estimate the relative bioefficacy of the two substrates for brain 22:6 accretion. Pregnant female baboons consumed a diet free of long chain ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:SW-13 adrenal tumor cells that lack detectable intermediate filaments (IF-free) exhibit an impaired capacity to esterify lipoprotein-derived cholesterol compared with cells that contain vimentin filaments. IF-free cells were found to synthesize and secrete significant amounts of apoE, while apoE secretion was nearly u...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-08-01 00:00:00
abstract：:Each abdominal fat depot, such as mesenteric or epididymal, differently contributes to the development of insulin resistance. The aim of this study was to identify the genetic regions that contribute to fat accumulation in epididymal/mesenteric fat and to examine whether or not the genetic regions that affect glucose ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M009563
更新日期：2010-12-01 00:00:00
abstract：:Liver and kidney microsomes have been found to catalyze a rapid decarboxylation of retinoic acid in vitro. The reaction requires NADPH and Fe(2+), and is further stimulated by the presence of pyrophosphate. Thiamine pyrophosphate contained sufficient iron as an impurity to provide strong enhancement of the reaction in...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1968-07-01 00:00:00
abstract：:HDL subspecies Lp(A-I) and Lp(A-I,A-II) have different anti-atherogenic potentials. To determine the role of lipoprotein lipase (LPL) and hepatic lipase (HL) in regulating these particles, we measured these enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and studied their relationship wi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300091-JLR200
更新日期：2003-08-01 00:00:00
abstract：:There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for this "HDL hypothesi...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R001610
更新日期：2010-08-01 00:00:00
abstract：:Lipid and cholesterol metabolism in the postprandial phase is associated with both quantitative and qualitative remodeling of HDL particle subspecies that may influence their anti-atherogenic functions in the reverse cholesterol transport pathway. We evaluated the capacity of whole plasma or isolated HDL particles to ...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.P009746
更新日期：2010-11-01 00:00:00
abstract：:Two procedures were used to isolate hepatocytic Golgi fractions from rat liver. One procedure yields a light Golgi fraction (GF1 + 2) and the other "intact" stacks of cisternae. Triglyceride fatty acids in nascent very low density lipoproteins (VLDL) were labeled by injection of [3H]palmitate intravenously, and radiol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:Lipogenesis in vitro from acetate-1-(14)C was studied in human preputial skin and abdominal skin. Radioactive lipids were separated by column chromatography on Florisil and by thin-layer chromatography on silica gel. Radioactivity was incorporated chiefly into the triglyceride, sterol, and polar lipid fractions, while...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-09-01 00:00:00
abstract：:The metabolism of chenodeoxycholic acid by Pseudomonas sp. NCIB 10590 under strict anaerobic conditions was studied. A range of unsaturated acidic and neutral metabolites were isolated and identified. The major acidic product was chola-4,6-dien-3-one-24-oic acid whilst the major neutral product was androsta-4,6-dien-3...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:In a randomized, cross-over feeding trial involving 10 men with polygenic hypercholesterolemia, a control, Mediterranean-type cholesterol-lowering diet, and a diet of similar composition in which walnuts replaced approximately 35% of energy from unsaturated fat, were given for 6 weeks each. Compared with the control d...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2001-12-01 00:00:00
abstract：:In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profiles in 24 models. These included five mouse strains, six other nonprimate specie...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M019927
更新日期：2012-01-01 00:00:00
abstract：:Changes in the cellularity of various adipose tissues in growing cattle were analyzed. Fifty male cattle were slaughtered between 15 and 65% of mature weight. The whole adipose mass, separated by dissection, was divided into three parts: subcutaneous, intermuscular, and internal adipose tissues. Lipid content, cell si...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:The action of cycloheximide on some parameters of glucose and lipid metabolism was studied in vitro in epidiymal fat pads from fasted rats. Incubation of fat pads with cycloheximide (1 mug/ml) for 2 hours resulted in a two-fold increase in glucose uptake, glucose oxidation, incorporation of glucose into lipids, and re...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1977-01-01 00:00:00
abstract：:Analysis of plasma nonesterified fatty acids (NEFA) by gas-liquid chromatography requires procedures that are both lengthy and cumbersome. A 45-min direct methylation procedure was carried out at 24-29 degrees C on 150 microliter of plasma added with an internal standard in 5.0 ml of methanol-acetyl chloride 50:1 (v/v...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:This paper presents a case of typical hyperlipoproteinemia type I in a young woman. Her serum triglycerides varied between 2 and 90 mmol/l and she had substantial amounts of apolipoprotein B-48 in fasting plasma. She had no detectable lipoprotein lipase (LPL) activity in post-heparin plasma (less than 0.2 percent of n...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation. PCSK9 is transcriptionally activated by sterol response element-bin...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.P009860
更新日期：2010-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-11-01 00:00:00
abstract：:Recent findings suggest that the effects of cholestyramine and psyllium in combination could be additive for cholesterol-lowering. We therefore examined the effect of both agents, alone and in combination, on lipoprotein cholesterol and neutral and acidic steroid excretion in the hamster. Animals (n = 8/group) were fe...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:Hepatic steatosis is one of the most common liver disorders in the general population. The main cause of hepatic steatosis is nonalcoholic fatty liver disease (NAFLD), representing the hepatic component of the metabolic syndrome, which is characterized by type 2 diabetes, obesity, and dyslipidemia. Insulin resistance ...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R008896
更新日期：2011-04-01 00:00:00
abstract：:The skin surface represents our interface with the external environment, and as such, is our first line of defense against microbial colonization and infection. Lipids at the skin surface are thought to underlie at least part of an antimicrobial barrier. Some of these lipids are synthesized in the epidermis and are ca...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R700016-JLR200
更新日期：2008-01-01 00:00:00
abstract：:The binding of monoacylglycerides of long-chain fatty acids to human serum albumin has been examined using monooleoylglycerol as the ligand. Binding was investigated using changes in tryptophan fluorescence and also the displacement of a variety of well-studied fluorescent ligands from human serum albumin (HSA). Monoo...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:Although the synthesis pathways of intracellular triacylglycerol (TAG) species have been well elucidated, assessment of the contribution of an individual pathway to TAG pools in different mammalian organs, particularly under pathophysiological conditions, is difficult, although not impossible. Herein, we developed and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M033837
更新日期：2013-04-01 00:00:00
abstract：:Apolipoprotein (apo) A-I-containing lipoproteins can be separated into two subfractions, pre-beta HDL and alpha HDL (high density lipoproteins), based on differences in their electrophoretic mobility. In this report we present results indicating that these two subfractions are metabolically linked. When plasma was inc...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-12-01 00:00:00
abstract：:Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by hum...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M009175
更新日期：2011-06-01 00:00:00
