Abstract:
:Lipoprotein lipase (LPL) is a key regulator of triglyceride clearance. Its coordinated regulation during feeding and fasting is critical for maintaining lipid homeostasis and energy supply. Angiopoietin-like (Angptl)3 and Angptl4 are secreted proteins that have been demonstrated to regulate triglyceride metabolism by inhibiting LPL. We have taken a targeted genetic approach to generate Angptl4- and Angptl3-deficient mice as well as transgenic mice overexpressing human Angptl4 in the liver. The Angptl4 transgenic mice displayed elevated plasma triglycerides and reduced postheparin plasma (PHP) LPL activity. A purified recombinant Angptl4 protein inhibited mouse LPL and recombinant human LPL activity in vitro. In contrast to the transgenic mice, Angptl4-deficient mice displayed hypotriglyceridemia and increased PHP LPL activity, with greater effects in the fasted compared with the fed state. Angptl3-deficient mice also displayed hypotriglyceridemia with elevated PHP LPL activity, but these mice showed a greater effect in the fed state. Mice deficient in both Angptl proteins showed an additive effect on plasma triglycerides and did not survive past 2 months of age. Our results show that Angptl3 and Angptl4 function to regulate circulating triglyceride levels during different nutritional states and therefore play a role in lipid metabolism during feeding/fasting through differential inhibition of LPL.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Köster A,Chao YB,Mosior M,Ford A,Gonzalez-DeWhitt PA,Hale JE,Li D,Qiu Y,Fraser CC,Yang DD,Heuer JG,Jaskunas SR,Eacho Pdoi
10.1210/en.2005-0476subject
Has Abstractpub_date
2005-11-01 00:00:00pages
4943-50issue
11eissn
0013-7227issn
1945-7170pii
en.2005-0476journal_volume
146pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::We previously reported that TNF-alpha-induced apoptosis of lactotropes is estrogen dependent and predominant at proestrus. Here we observed that TNF-alpha (50 ng/ml) failed to induce apoptosis of anterior pituitary cells from ovariectomized rats cultured in the presence of progesterone (10(-6) m). However, progesteron...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-1276
更新日期:2005-02-01 00:00:00
abstract::High-density lipoprotein mediates a normal physiological process called reverse cholesterol transport. This process enables the transfer of cholesterol from peripheral tissues to the liver for further metabolism and eventual secretion in the form of bile. The scavenger receptor of the B class (SR-BI), human homolog of...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-0330
更新日期:2004-12-01 00:00:00
abstract::In order to elucidate potential sites of direct GH action on the kidney, we used in situ hybridization to localize GH receptor (GHR) gene expression during the course of development and in the adult rat. In order to illuminate potential interactions between GH and insulin-like growth factor-I (IGF-I) in regulating ren...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.6.1446640
更新日期:1992-12-01 00:00:00
abstract::The effects of nerve activation and of the catecholamines epinephrine and norepinephrine on adrenal corticosteroid release were investigated in intact isolated perfused pig adrenals with preserved nerve supply. To study the contact zones of medullary and cortical tissues, porcine adrenals were examined on the histolog...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-127-2-900
更新日期:1990-08-01 00:00:00
abstract::The effects of FFA on circulating LH and GH concentrations in ovariectomized ewe lambs were investigated. Lambs (n = 14) were weaned at 2.5 months, ovariectomized at 6.5 months, and used at 8.5 months of age. From weaning until day 0 of the experiment, lambs were fed to maintain body weights (23 kg). On day 0, serum F...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-4-1934
更新日期:1990-04-01 00:00:00
abstract::The epidermis has a great potential as a bioreactor to produce proteins with systemic action. However, the consequences of ectopic epidermal protein overexpression need to be carefully addressed to avoid both local and systemic adverse effects. Thus, the long-term effects of leptin on skin physiology have not been stu...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0156
更新日期:2005-10-01 00:00:00
abstract::Hypothalamic enzymatic activities capable of degrading LHRH may play a physiological role in the neuroendocrine control of LHRH. There is increasing evidence, however, that these enzymes are not peptide specific. The present study in the ewe analyzed the possibility that the specificity of LHRH-degrading activity (LHR...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-6-2410
更新日期:1985-06-01 00:00:00
abstract::It is still controversial whether the bone-derived hormone fibroblast growth factor-23 (FGF23) has additional physiological functions apart from its well-known suppressive actions on renal phosphate reabsorption and vitamin D hormone synthesis. Here we analyzed premature aging, mineral homeostasis, carbohydrate metabo...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1878
更新日期:2012-04-01 00:00:00
abstract::Pancreastatin, a novel 49-amino acid peptide isolated from porcine pancreas, shows over 70% sequence homology to the central part of bovine and human chromogranin-A. Using an N-terminal and C-terminal synthetic peptide, we developed two sensitive and specific RIAs for the detection of pancreastatin-like immunoreactivi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-123-3-1395
更新日期:1988-09-01 00:00:00
abstract::The participation of growth factors in wound healing and tissue repair has been well established. Previous studies demonstrated that the expression of keratinocyte growth factor (KGF) was greatly elevated shortly after injury and that topical application of KGF accelerated healing. Steroidal antiinflammatory agents, s...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.6.8641170
更新日期:1996-06-01 00:00:00
abstract::This study investigates the signaling pathways that lead to acute augmentation of secretagogue-induced LH secretion, the physiologically relevant manifestation of which is LHRH self-potentiation. The consequence of LHRH self-potentiation is an augmented LH secretory response to subsequent exposure to the peptide. Alth...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.6.1317780
更新日期:1992-06-01 00:00:00
abstract::In the murine Ob 17 preadipocyte cell line, the thyroid hormone T3 is an adipogenic factor necessary at an early stage for differentiation into adipocyte. We demonstrate here that this T3 dependence may involve a transient expression (at both the messenger RNA and the protein levels) of c-ErbA beta-type receptors (T3R...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.7.6860
更新日期:1999-07-01 00:00:00
abstract::A novel class of targeted chemotherapeutic agents based on cytotoxic compounds linked to LHRH analogs was tested in a long term superfusion system in order to determine their effects on different types of rat pituitary cells. The compounds investigated included two cytotoxic LHRH agonists, T-98 ([D-Lys6]LHRH coupled t...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.132.5.8477650
更新日期:1993-05-01 00:00:00
abstract::The human estrogen receptor alpha (ERalpha) and the recently identified ERbeta share a high degree of amino acid homology; however, there are significant differences in regions of these receptors that would be expected to influence transcriptional activity. Consequently, we compared the mechanism(s) by which these rec...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.12.7179
更新日期:1999-12-01 00:00:00
abstract::Testicular LH receptor occupancy and steroidogenic responses were measured in adult male rats after intracardiac injections of [125I]iodo-hCG (0.5--5 x 10(6) cpm) mixed with known amounts of nonradioactive hCG to yield doses ranging from 10 ng to 300 micrograms. Uptake of the hormone by the testis was measured in the ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-111-3-982
更新日期:1982-09-01 00:00:00
abstract::To assess the possible source of progesterone in the fetal fluids of pregnant sheep, we measured the changes in progesterone concentrations in amniotic fluid (AF) and allantoic fluid (ALF) during pregnancy and compared these values with those in the maternal and fetal circulations. In acute experiments, the concentrat...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-110-2-481
更新日期:1982-02-01 00:00:00
abstract::The thyroid hormone (TH) analog eprotirome (KB2115) was developed to lower cholesterol through selective activation of the TH receptor (TR) β1 in the liver. Interestingly, eprotirome shows low uptake in nonhepatic tissues, explaining its lipid-lowering action without adverse extrahepatic thyromimetic effects. Clinical...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2017-00433
更新日期:2017-10-01 00:00:00
abstract::Because there are sex differences in feeding behavior in rats, we looked for a possible sex difference in the response to glucose of melanin-concentrating hormone (MCH) neurons in the lateral hypothalamic area using phosphorylated cAMP response element-binding protein (pCREB) as a marker of neural activity. Intact mal...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0078
更新日期:2005-08-01 00:00:00
abstract::As part of an ongoing investigation of the role of metabolic activation of estrogens in the genesis of cancers such as estrogen-induced renal tumors in hamsters, we have 1) determined steroid-17 beta-oxidoreductase activity of microsomes and cytosol prepared from hamster kidney and liver; 2) compared the rates of 2-, ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.5.7956900
更新日期:1994-11-01 00:00:00
abstract::The dynamics of dopamine (DA) action on PRL release was studied in superfused rat anterior pituitary cell aggregates, cultured for for 5 days either in conventional or in serum-free defined medium. In aggregates cultured in conventional medium 0.1-1 nM DA applied for 20 min provoked a rapid and concentration-dependent...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-114-4-1371
更新日期:1984-04-01 00:00:00
abstract::Ghrelin is more effective than GHRH in stimulating GH release in normal adult humans and monkeys in vivo. This robust effect of ghrelin has been largely attributed to regulation of hypothalamic input, whereas the direct effect of ghrelin on pituitary GH release has been minimized by the observation that ghrelin has on...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-0441
更新日期:2007-09-01 00:00:00
abstract::The proliferation and differentiation of testicular progenitor stem cells into highly specialized germ cells (spermatozoa) are largely controlled by the hormonally (FSH and testosterone) regulated adjacent supporting Sertoli cells. However, the factors involved in this control remain largely unknown. In the present st...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.8.7625
更新日期:2000-08-01 00:00:00
abstract::During luteinization of bovine granulosa cells in vitro in the presence of insulin, or insulin plus forskolin, there is a massive upregulation not only of progesterone production, but also of the gene for the peptide hormone oxytocin, with secretion of the peptide into the medium. By using the progesterone receptor an...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.11.5650
更新日期:1997-11-01 00:00:00
abstract::Gene expression of fibroblast growth factor-9 (FGF9) is decreased in granulosa cells (GC) of cystic follicles compared with normal dominant follicles in cattle. The objectives of this study were to investigate the effects of FGF9 on GC steroidogenesis, gene expression, and cell proliferation and to determine the hormo...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-1003
更新日期:2012-09-01 00:00:00
abstract::The nuclear orphan receptor human estrogen receptor-related receptor (ERR)-alpha is implicated in bone metabolism. We studied the effect of ERRalpha silencing in human mesenchymal stem cells (hMSCs) during osteoblastogenesis. We found that ERRalpha silencing led to an increase of bone sialoprotein and a decrease of os...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0121
更新日期:2009-10-01 00:00:00
abstract::Somatostatin has been demonstrated to negatively regulate pancreatic growth in vivo. In this study we used the AR4-2J rat pancreatic acinar tumor cell line to investigate the effect of a stable somatostatin analog, SMS 201-995 (SMS) on cell proliferation. SMS induced an antiproliferative effect on both serum or epider...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-2-1017
更新日期:1989-02-01 00:00:00
abstract::Specific binding sites for PRL were identified on isolated intestinal epithelial cells from both male and female rabbits. These receptors exhibited a very high affinity for PRL (Kd = 5 x 10(-11) M) and were immunologically very similar to the well characterized mammary PRL receptor. About 3500 PRL receptors/cell were ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.5.1572300
更新日期:1992-05-01 00:00:00
abstract::The study of epigenetics allows for the understanding of gene × environmental interactions and provides a mechanism by which brief internal or external environmental changes can shape lasting differences in gene function and behavior. Epigenetic processes appear to impact a wide variety of physiological processes with...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2010-0793
更新日期:2011-02-01 00:00:00
abstract::In mammals, skeletal muscle mass is negatively regulated by a muscle-derived growth/differentiating factor named myostatin (MSTN) that belongs to the transforming growth factor-beta superfamily. Although putative MSTN homologs have been identified from several vertebrates, nonmammalian orthologs remained poorly define...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.4.8097
更新日期:2001-04-01 00:00:00
abstract::Recent studies using twins and inbred strains of mice reveal evidence for genetic mechanisms contributing to variation in circulating levels of IGF-I, IGF-II, and IGF binding protein (IGFBP)-3. To examine the hypothesis that serum IGFBP-5 levels have a strong heritable component, we intercrossed two inbred strains of ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-0042
更新日期:2003-08-01 00:00:00