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《Journal of lipid research》2017,58(12):2348-2364
Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase (PAP) that in mice is necessary for normal glycerolipid biosynthesis, controlling adipocyte metabolism, and adipogenic differentiation. Mice carrying inactivating mutations in the Lpin1 gene display the characteristic features of human familial lipodystrophy. Very little is known about the roles of lipin-1 in human adipocyte physiology. Apparently, fat distribution and weight is normal in humans carrying LPIN1 inactivating mutations, but a detailed analysis of adipose tissue appearance and functions in these patients has not been available so far. In this study, we performed a systematic histopathological, biochemical, and gene expression analysis of adipose tissue biopsies from human patients harboring LPIN1 biallelic inactivating mutations and affected by recurrent episodes of severe rhabdomyolysis. We also explored the adipogenic differentiation potential of human mesenchymal cell populations derived from lipin-1 defective patients. White adipose tissue from human LPIN1 mutant patients displayed a dramatic decrease in lipin-1 protein levels and PAP activity, with a concomitant moderate reduction of adipocyte size. Nevertheless, the adipose tissue develops without obvious histological signs of lipodystrophy and with normal qualitative composition of storage lipids. The increased expression of key adipogenic determinants such as SREBP1, PPARG, and PGC1A shows that specific compensatory phenomena can be activated in vivo in human adipocytes with deficiency of functional lipin-1. 相似文献
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Zhi H. Huang Catherine A. Reardon Godfrey S. Getz Nobuyo Maeda Theodore Mazzone 《Journal of lipid research》2015,56(2):215-226
apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state. 相似文献
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Misato Hirano Junko Shibato Randeep Rakwal Nobuo Kouyama Yoko Katayama Motohiro Hayashi Yoshinori Masuo 《Molecules and cells》2009,27(2):263-268
Gamma knife surgery (GKS) is used for the treatment of various human brain disorders. However, the biological effects of gamma
ray irradiation on both the target area, and the surrounding tissues are not well studied. The effects of gamma ray exposure
to both targeted and untargeted regions were therefore evaluated by monitoring gene expression changes in the unilateral irradiated
(60 Gy) and contralateral un-irradiated striata in the rat. Striata of irradiated and control brains were dissected 16 hours
post-irradiation for analysis using a whole genome 44K DNA oligo microarray approach. The results revealed 230 induced and
144 repressed genes in the irradiated striatum and 432 induced and 239 repressed genes in the un-irradiated striatum. Out
of these altered genes 39 of the induced and 16 of the reduced genes were common to both irradiated and un-irradiated tissue.
Results of semiquantitative, confirmatory RT-PCR and western blot analyses suggested that γ-irradiation caused cellular damage,
including oxidative stress, in the striata of both hemispheres of the brains of treated animals. 相似文献
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V. M. Philip S. Duvvuru B. Gomero T. A. Ansah C. D. Blaha M. N. Cook K. M. Hamre W. R. Lariviere D. B. Matthews G. Mittleman D. Goldowitz E. J. Chesler 《Genes, Brain & Behavior》2010,9(2):129-159
Genetic reference populations, particularly the BXD recombinant inbred (BXD RI) strains derived from C57BL/6J and DBA/2J mice, are a valuable resource for the discovery of the bio‐molecular substrates and genetic drivers responsible for trait variation and covariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict the occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic coregulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium (TMGC) have obtained phenotype data from over 250 measures related to multiple behavioral assays across several batteries: response to, and withdrawal from cocaine, 3,4‐methylenedioxymethamphetamine; “ecstasy” (MDMA), morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity and sleep/wake cycles. All traits have been measured in both sexes in approximately 70 strains of the recently expanded panel of BXD RI strains. Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent (N = 37) BXD RI lines was performed. Primary data are publicly available for heritability, sex difference and genetic analyses using the MouseTrack database, and are also available in GeneNetwork.org for quantitative trait locus (QTL) detection and genetic analysis of gene expression. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits. 相似文献
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Duran-Montgé P Theil PK Lauridsen C Esteve-Garcia E 《Animal : an international journal of animal bioscience》2009,3(11):1580-1590
It has been shown previously that lipid metabolism is regulated by fatty acids (FA) and that thyroid hormones are important regulators of energy metabolism. The effects of weight, dietary fat level and dietary FA profile on thyroid hormone levels and expression of lipogenic genes and tissue FA composition were studied. Sixty-one crossbred gilts weighing 62 ± 5.2 kg BW average were either slaughtered at the beginning of the trial (n = 5) or fed one of seven diets (n = 8 pigs per diet): a semi-synthetic diet formulated to contain a very low level of fat (NF) and six diets based on barley-soybean meal supplemented with approximately 10% fat of different origin and slaughtered at 100 kg BW. The supplemental fats were tallow, high-oleic sunflower oil, sunflower oil (SFO), linseed oil, fat blend (55% tallow, 35% sunflower oil, 10% linseed oil) and fish oil blend (40% fish oil, 60% linseed oil). In general, the dietary FA profiles altered the FA composition of liver, semimembranosus muscle and adipose tissues. Pigs fed the NF diet had the highest free and total triiodothyronine (T3) values followed by pigs fed SFO. Total T3 levels were higher in pigs at 60 kg than in pigs at 100 kg. Correlations between thyroid hormones and genes encoding enzymes of fat synthesis in adipose tissue (acetyl CoA carboxylase (ACACA), fatty acid synthase and stearoyl CoA desaturase (SCD)) and the large differences in expression of lipogenic genes at different weights (60 and 100 kg BW), suggest a role for thyroid hormones and for T3, in particular, in regulating whole animal fat metabolism, with effects brought about by altered expression of lipogenic genes. Liver sterol receptor element binding protein-1 (SREBP1) mRNA content was affected by dietary treatment (P < 0.001) and was correlated with ACACA and SCD, whereas adipose tissue SREBP1 was not correlated with the mRNA abundance of any lipogenic enzyme. Weight and tissue factors showed greater influence on mRNA abundance of genes related with lipid metabolism than diet and tissue FA composition. In the pig, FA synthesis appear to be of greater magnitude in adipose tissue than in the liver as suggested by the higher expression of lipogenic genes in adipose tissue. 相似文献
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Wang HB Wang QG Zhang XY Gu XF Wang N Wu SB Li H 《Animal : an international journal of animal bioscience》2010,4(4):513-522
Excessive accumulation of lipids in the adipose tissue is one of the main problems faced by the broiler industry nowadays. In chicken, lipogenesis occurs essentially in the liver, in which much of the triglycerides that accumulate in avian adipose tissue are synthesized. In order to better understand the gene expression and its regulation in chicken liver, the gene expression profiles of liver at developmental stages of chicken (1 week, 4 weeks and 7 weeks of age) were investigated and differentially expressed genes between lean and fat chicken lines divergently selected for abdominal fat content for eight generations were screened. Our data indicated that 4 weeks of age was a very important stage on chicken liver lipogenesis compared to 1 week and 7 weeks of age, and the glycometabolism in chicken liver could be related to lipid metabolism and the difference of glycometabolism could be another potential reason for the fat and lean phenotype occurrence besides the difference of lipogenesis in chicken liver. Our result have established groundwork for further study of the basic genetic control of chicken obesity and will benefit chicken research communities as well as researches that use chicken as a model organism for developmental biology and human therapeutics. 相似文献
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Maureen Friedrichs Isa Kolbe Julia Seemann Anthony H. Tsang Lisa Cherradi Johannes Klein 《Chronobiology international》2013,30(11):1543-1552
ABSTRACTCircadian clock-controlled 24-h oscillations in adipose tissues play an important role in the regulation of energy homeostasis, thus representing a potential drug target for prevention and therapy of metabolic diseases. For pharmacological screens, scalable adipose model systems are needed that largely recapitulate clock properties observed in vivo. In this study, we compared molecular circadian clock regulation in different ex vivo and in vitro models derived from murine adipose tissues. Explant cultures from three different adipose depots of PER2::LUC circadian reporter mice revealed stable and comparable rhythms of luminescence ex vivo. Likewise, primary pre- and mature adipocytes from these mice displayed stable luminescence rhythms, but with strong damping in mature adipocytes. Stable circadian periods were also observed using Bmal1-luc and Per2-luc reporters after lentiviral transduction of wild-type pre-adipocytes. SV40 immortalized adipocytes of murine brown, subcutaneous and epididymal adipose tissue origin showed rhythmic mRNA expression of the core clock genes Bmal1, Per2, Dbp and REV-erbα in pre- and mature adipocytes, with a maturation-associated increase in overall mRNA levels and amplitudes. A comparison of clock gene mRNA rhythm phases revealed specific changes between in vivo and ex vivo conditions. In summary, our data indicate that adipose culture systems to a large extent mimic in vivo tissue clock regulation. Thus, both explant and cell systems may be useful tools for large-scale screens for adipose clock regulating factors. 相似文献
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We have examined the incorporation and metabolism of [14C] stearic acid within the total lipids of HTC rat-hepatoma cells in suspension culture in presence and in absence of steroidal hormone stimulation. Both, glucocorticoids (dexamethasone, cortisol and corticosterone) and mineralocorticoids (deoxycorticosterone and aldosterone) as well as the estrogen -estradiol and the androgen testosterone enhanced the extent of 9 desaturation to oleic acid of the saturated precursors, whereas only the two mineralocorticoids affected the incorporation rate of the exogenous acid into total cellular lipids, thus promoting a little stimulation. Furthermore, all the hormones tested increased the radiolabelling of the total cellular phospholipids except deoxycorticosterone and testosterone, the former having no effect and the latter exerting a moderate inhibition. On the other hand, the incorporation of14C into neutral lipids was stimulated by testosterone, in contrast to the inhibition of this parameter observed exclusively with either the mineralocorticoids or the estrogen. Within the phospholipid subclasses, the radiolabelling of phosphatidylcholine was augmented by means of all the steroids tested save deoxycorticosterone and testosterone, whereas phosphatidylethanolamine exhibited a decrease only in the presence of testosterone. In a similar fashion, within the neutral lipids, the predominating triglyceride fraction was preferentially labelled—at the expense of other subclasses of lesser abundance—upon treatment with the steroids except aldosterone, which exerted no effect. The results obtained were correlated with those changes observed in the mass distribution of the different lipid subclasses either with or without prior hormonal stimulation.Abbreviations ALD
aldosterone
- ANOVAR
analyses of variance
- CE
cholesterol esters
- Cl
cortisol
- CLN
cardiolipin
- Cst
corticosterone
- CH
cholesterol
- DG
diacylglycerides
- DOC
11-deoxycorticosterone
- Dx
dexamethasone phosphate salt
- ßE
17--estradiol
- FAME
fatty acid methyl esters
- GLC
gas-lipid chromatography
- HEPES
N-2-hydroxyethyl-piperazine-N-2-ethanosulfonic acid
- HTC
hepatoma tissue culture
- IMEM-Zo
improved minimal essential medium-Zinc option
- LPC
lysophosphatidyl-choline
- LPL
lysophospholipids
- MG
monoacylglycerides
- NEFA
free fatty acids
- PC
phosphatidyl-choline
- PE
phosphatidyl-ethanolamine
- PG
phosphatidyl-glycerol
- PI
phosphadyl-inositol
- PS
phosphadidyl-serine
- SM
sphingomyelin
- TG
triacylglycerides
- TLC
thin-layer chromatography
- Tst
testosterone
Members of the Carrera del Investigador Cientifico, CONICET, Argentina. 相似文献
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Lahoucine Izem Diane J. Greene Katarzyna Bialkowska Richard E. Morton 《Journal of lipid research》2015,56(3):515-525
Cells produce two cholesteryl ester transfer protein (CETP) isoforms, full-length and a shorter variant produced by alternative splicing. Blocking synthesis of both isoforms disrupts lipid metabolism and storage. To further define the role of CETP in cellular lipid metabolism, we stably overexpressed full-length CETP in SW872 cells. These CETP+ cells had several-fold higher intracellular CETP and accumulated 50% less TG due to a 26% decrease in TG synthesis and 2.5-fold higher TG turnover rate. Reduced TG synthesis was due to decreased fatty acid uptake and impaired conversion of diglyceride to TG even though diacylglycerol acyltransferase activity was normal. Sterol-regulatory element binding protein 1 mRNA levels were normal, and although PPARγ expression was reduced, the expression of several of its target genes including adipocyte triglyceride lipase, FASN, and APOE was normal. CETP+ cells contained smaller lipid droplets, consistent with their higher levels of perilipin protein family (PLIN) 3 compared with PLIN1 and PLIN2. Intracellular CETP was mostly associated with the endoplasmic reticulum, although CETP near lipid droplets poorly colocalized with this membrane. A small pool of CETP resided in the cytoplasm, and a subfraction coisolated with lipid droplets. These data show that overexpression of full-length CETP disrupts lipid homeostasis resulting in the formation of smaller, more metabolically active lipid droplets. 相似文献
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H. Ling K. Zuo J. Zhao J. Qin C. Qiu X. Sun K. Tang 《Russian Journal of Plant Physiology》2006,53(3):366-372
Lipase is an important lipolytic enzyme involved in plant lipid metabolism. To analyze its function and roles during seed
germination and growth, a full-length cDNA encoding a homologous to lipase gene named BnLIP1 was cloned from Brassica napus, cv. Huyou 15, by rapid amplification of cDNA ends. The BnLIP1 gene had a total length of 1318 bp, with an open reading frame of 1170 bp encoding 389 amino acid residues. Sequence analysis
revealed that BnLIP1 protein belonged to the GDSL family of serine esterases/lipases. In B. napus genome, BnLIP1 is represented by several copies with the length of 1601 bp, the gene comprises five exons and four introns. RT-PCR analysis
indicated that BnLIP1 showed no tissue-specific expression during reproductive growth and is strongly expressed during seed germination. No expression
could be detected until three days after germination, and its peak was registered at the fifth day after germination. In conclusion,
BnLIP1-encoded protein is predicted to be a lipolytic enzyme widely expressed at various stages of oilseed rape germination and
development.
Published in Russian in Fiziologiya Rastenii, 2006, Vol. 53, No. 3, pp. 410–417.
The text was submitted by the authors in English. 相似文献