Abstract：
:The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE*3-Leiden.CETP transgenic mice were fed a Western-type diet for 4 weeks and infused intracerebroventricularly with the melanocortin 3/4 receptor (MC3/4R) antagonist SHU9119 or vehicle for 2 weeks. SHU9119 increased food intake (+30%) and body fat (+50%) and decreased EE by reduction in fat oxidation (-42%). In addition, SHU9119 impaired the uptake of VLDL-TG by BAT. In line with this, SHU9119 decreased uncoupling protein-1 levels in BAT (-60%) and induced large intracellular lipid droplets, indicative of severely disturbed BAT activity. Finally, SHU9119-treated mice pair-fed to the vehicle-treated group still exhibited these effects, indicating that MC4R inhibition impairs BAT activity independent of food intake. These effects were not specific to the APOE*3-Leiden.CETP background as SHU9119 also inhibited BAT activity in wild-type mice. We conclude that inhibition of central MC3/4R signaling impairs BAT function, which is accompanied by reduced EE, thereby promoting adiposity. We anticipate that activation of MC4R is a promising strategy to combat obesity by increasing BAT activity.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Kooijman S,Boon MR,Parlevliet ET,Geerling JJ,van de Pol V,Romijn JA,Havekes LM,Meurs I,Rensen PCdoi
10.1194/jlr.M045989subject
Has Abstractpub_date
2014-10-01 00:00:00pages
2022-32issue
10eissn
0022-2275issn
1539-7262pii
jlr.M045989journal_volume
55pub_type
杂志文章abstract：:The activities of hepatic fatty acid oxidation enzymes in rats fed perilla oil rich in alpha-linolenic acid (alpha-18:3) were compared with those fed saturated fats or safflower oil (the mixture of safflower oil and olive oil, 94:8, w/w) containing the same amount of polyunsaturated fatty acids with perilla oil exclus...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:We report the characterization of eight mutations of sterol 27-hydroxylase gene (CYP27) in five Italian patients with cerebrotendinous xanthomatosis, who were found to be compound heterozygotes. Four mutations (C --> T at nt 45 of exon 4, G(+1) --> A in intron 6, G(+5) --> T in intron 7, and G(-1) --> A in intron 7) a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：:In mammals, because they share a single synthetic pathway, n-6/n-3 ratios of dietary PUFAs impact tissue arachidonic acid (ARA) and DHA content. Likewise, SNPs in the human fatty acid desaturase (FADS) gene cluster impact tissue ARA and DHA. Here we tested the feasibility of using heterozygous Fads2-null-mice (HET) as...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M064956
更新日期：2016-11-01 00:00:00
abstract：:The storage of lipids in the form of triglycerides (TGs) and the de novo synthesis (lipogenesis) of fatty acids from nonlipid precursors [de novo lipogenesis (DNL)] are important functions of adipose tissue (AT) that influence whole-body metabolism. Yet, few studies have reported in vivo estimates of adipose lipid kin...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P082628
更新日期：2018-09-01 00:00:00
abstract：:Incubation of 125I-labeled very low density lipoprotein (VLDL) with lipoprotein lipase-rich (postheparin) plasma obtained from intact or supradiaphragmatic rats resulted in the transfer of more than 80% of apoprotein C from VLDL to high density lipoprotein (HDL), whereas apoprotein B was associated with lipoprotein of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-09-01 00:00:00
abstract：:Blood levels of lipoprotein cholesterol and triglycerides (TGs) are highly heritable and are major risk factors for cardiovascular disease (CVD). Approximately 100 lipid-associated loci have been identified in populations of European ancestry. We performed a genome-wide association study of lipid traits in 1,782 Filip...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P042077
更新日期：2013-11-01 00:00:00
abstract：:The chromatographic behavior of 1,2-, 1,3-, 1,4-, and 1,12-long-chain alkane diols and 1-O-alkylglycerols and their derivatives has been compared. Thin-layer chromatography on Silica Gel G gives poor separations of the 1,2-, 1,3-, and 1,4-alkane diols, O-alkylglycerols, and some of their isopropylidene derivatives. Ho...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1971-09-01 00:00:00
abstract：:The increased generation of reactive oxygen species that occurs in the condition of obesity may be responsible for oxidative injury to erythrocyte membranes, which could lead to a decrease in tissue oxygenation. Therefore, we have looked into the effects of obesity on both indexes of oxidative damage and physical-chem...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300509-JLR200
更新日期：2004-10-01 00:00:00
abstract：:Apoliprotein (apo) B-100-containing very low density lipoprotein (VLDL) particles secreted from the liver accumulate in plasma during alimentary lipemia. To determine whether changes of VLDL composition occur in the postprandial state that may render these lipoproteins more atherogenic, apoE, C-I, C-II, and C-III, and...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
abstract：:Four distinct subspecies of the insect hemolymph lipoprotein, lipophorin, that range in diacylglycerol (DAG) content from approximately 100 to 1000 molecules per particle, were treated with phospholipase C. Lipid analysis demonstrated that both phosphatidylcholine and phosphatidylethanolamine were hydrolyzed to DAG. P...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:The characteristics of 7 alpha-dehydroxylase, a bile acid-biotransforming enzyme, were determined using dialyzed cell extracts of Eubacterium sp. V.P.I. 12708. 7 alpha-Dehydroxylase was induced by cholic acid in this organism. Induction by cholic acid resulted in the differential synthesis of at least five new polypep...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:Oxidative stress promotes acute kidney injury (AKI). Higher concentrations of HDL cholesterol are associated with less AKI. To test the hypothesis that HDL antioxidant activity is associated with AKI after cardiac surgery, we quantified HDL particle size and number, paraoxonase-1 activity, and isofuran concentrations ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1016/j.jlr.2021.100024
更新日期：2021-01-13 00:00:00
abstract：:The hydrolysis of HDL phospholipids (PL) and glycerides by hepatic lipase (HL) has been investigated in native and reconstituted HDL particles (Lp2A-I). Fasting, normolipidemic HDL exhibit total lipid hydrolytic rates of between 10 and 36 nM FA/h per microM PL. Of the total fatty acids liberated with HDL3 only 1% are ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：:A series of cholesterol hydroperoxides has been prepared and tested as inactivators of calmodulin. Two previously undescribed compounds, tentatively identified as 20-(R)-25-dihydroperoxy-5-cholesten-3 beta-ol and its 20-(S) isomer inactivate calmodulin with 50% loss of activity at 5-10 microM. Cholesterol derivatives ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:It was postulated that specialized microdomains of the plasma membrane, consistent with caveolae, might play a role in cholesterol trafficking in intestinal cells. The existence, therefore, of caveolin and the role of detergent-resistant microdomains of the plasma membrane in cholesterol trafficking were investigated ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:The accumulation of phosphatidylcholine hydroperoxide (PCOOH), a primary oxidation product of phosphatidylcholine (PC), in blood plasma and tissues has been observed in various pathological conditions, including atherosclerosis. However, the biological roles of PCOOH in these conditions remain unknown. To estimate the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800582-JLR200
更新日期：2009-05-01 00:00:00
abstract：:The acute-phase response (APR) leads to alterations in lipid metabolism and type II nuclear hormone receptors, which regulate lipid metabolism, are suppressed, in liver, heart, and kidney. Here, we examine the effect of the APR in adipose tissue. In mice, lipopolysaccharide produces a rapid, marked decrease in mRNA le...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500540-JLR200
更新日期：2006-10-01 00:00:00
abstract：:A facile procedure is described for the preparation of [14C]epicholesterol from [14C]cholesterol. Cholesterol is first converted to cholesteryl mesylate, which is treated with cesium acetate and 18-crown-6 in refluxing toluene to give epicholesteryl acetate. The latter is hydrolyzed, without isolation, with potassium ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:We have previously observed that the Ya subunit-containing glutathione (GSH) S-transferases from rat liver exhibit a common high affinity binding site for lithocholic acid, bilirubin, and sulfobromophthalein (BSP) (1984. J. Lipid Res. 25: 1177-1183). Subsequently we found that cholic acid and its amidates bound to a s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:Monospecific antisera were produced to two chylomicron apoproteins (apoB, apoA-I) and utilized for indirect immunofluorescent localization of these apoproteins within rat intestinal epithelium during normal and impaired lipid absorption. Isolated intestinal epithelial cells prepared after different periods of lipid ab...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:LDL-associated phospholipids (PLs) may be transferred into platelets. In this work, we characterized the role of VLDLs as PL donors. VLDL transferred radiolabeled PLs to platelets in a temperature- and concentration-dependent manner. LPL stimulated this process through its action on VLDL lipolysis, because it was abol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500209-JLR200
更新日期：2006-02-01 00:00:00
abstract：:Lec9 Chinese hamster ovary cells were found previously to be defective in the synthesis of N-linked glycans. This appeared to be the result of a defect in the synthesis of oligosaccharide lipid and lipid phosphate (Rosenwald, Stanley, and Krag. 1989. Mol. Cell. Biol. 9: 914-924). In this study we analyzed the steady s...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Lilly PCSK9 antibody LY3015014 (LY) is a monoclonal antibody (mAb) that neutralizes proprotein convertase subtilisin-kexin type 9 (PCSK9). LY decreases LDL cholesterol in monkeys and, unlike other PCSK9 mAbs, does not cause an accumulation of intact PCSK9 in serum. Comparing the epitope of LY with other clinically tes...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M061903
更新日期：2015-11-01 00:00:00
abstract：:In skin fibroblasts grown from four children with a homozygous form of type II hyperlipoproteinemia, the feedback control of sterol synthesis and the inhibitory effect on hydroxymethylglutaryl (HMG) CoA reductase activity by serum or low density lipoprotein were present, though diminished compared with the effects in ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-03-01 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：:The direct non-endocytotic uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) plays a major role in HDL CE metabolism in rats and rabbits. In vitro evidence indicates it may also play such a role in humans. However, a study in mice (tracing the CE and apoA-I moieties of HDL) concluded that, while se...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Structurally specific very low density lipoprotein (VLDL) particles are presumed to redirect VLDL uptake during yolk deposition. Egg production is an energy intensive process, but energy excess negatively affects egg production. This study sought to determine whether overfeeding changed hen lipoprotein profiles, and i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:Chylomicron metabolism is critical for determining plasma levels of triacylglycerols (TAGs) and cholesterol, both of which are risk factors for CVD. The rates of chylomicron secretion and remnant clearance are controlled by intracellular and extracellular factors, including apoC-III. We have previously shown that huma...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M092460
更新日期：2019-09-01 00:00:00
abstract：:Activation of cultured hepatic stellate cells correlated with an enhanced expression of proteins involved in uptake and storage of fatty acids (FA translocase CD36, Acyl-CoA synthetase 2) and retinol (cellular retinol binding protein type I, CRBP-I; lecithin:retinol acyltransferases, LRAT). The increased expression of...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200376-JLR200
更新日期：2003-02-01 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
