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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zinc-alpha(2)-glycoprotein (ZAG), a lipid-mobilizing factor, is a novel adipokine which may act locally to influence adipose tissue metabolism. This study examined the ontogeny of ZAG expression in adipose tissue during postnatal development. White (subcutaneous, gonadal, and perirenal) and brown (interscapular) fat was collected from rats aged 1-32 days. ZAG mRNA was detected from day 1 in subcutaneous fat, which appears the key site of synthesis postnatally. ZAG was detected in perirenal (day 5) and in gonadal (day 7) fat when the tissue was sufficient for analysis. ZAG mRNA and protein levels fell significantly at weaning (day 21) and thereafter. ZAG was also detected in brown fat at day 1 but it fell significantly afterwards. The downregulated ZAG expression in white fat depots at weaning, when fat mass is expanded substantially, suggests that ZAG might be involved in the postnatal development of adipose tissue mass.
Mol Cell Endocrinol 2007 Dec 15
PMID:Postnatal expression of zinc-alpha2-glycoprotein in rat white and brown adipose tissue. 1793 67

Leptin is an adipokine that regulates food intake and energy expenditure by activating its hypothalamic leptin receptor (LR). Members of the insulin receptor substrate (IRS) family serve as adaptor proteins in the signaling pathways of several cytokines and hormones and a role for IRS2 in central leptin physiology is well established. Using mammalian protein-protein interaction trap (MAPPIT), a cytokine receptor-based two-hybrid method, in the N38 hypothalamic cell line, we here demonstrate that also IRS4 interacts with the LR. This recruitment is leptin dependent and requires phosphorylation of the Y1077 motif of the LR. Domain mapping of IRS4 revealed the critical role of the pleckstrin homology domain for full interaction. In line with its function as an adaptor protein, IRS4 interacted with the regulatory p85 subunit of the phosphatidylinositol 3-kinase, phospholipase Cgamma, and the suppressor of cytokine signaling (SOCS) family members SOCS2, SOCS6, and SOCS7 and thus can modulate LR signaling.
Mol Endocrinol 2008 Apr
PMID:Insulin receptor substrate 4 couples the leptin receptor to multiple signaling pathways. 1816 36

Adipokines are secreted by adipose tissue and control various physiological systems. Low leptin levels during fasting stimulate feeding, reduce energy expenditure, and modulate neuroendocrine and immune function to conserve energy stores. On the other hand, rising leptin levels in the overfed state prevent weight gain by inhibiting food intake and increasing energy expenditure. These actions are mediated by neuronal circuits in the hypothalamus and brainstem. Leptin also controls glucose and lipid metabolism by targeting enzymes such as AMP-activated protein kinase and stearoyl-coenzyme A desaturase-1 in liver and muscle. Likewise, adiponectin and resistin control energy balance and insulin sensitivity via central and peripheral targets. As highlighted in this review, there are distinct as well as common signaling pathways for adipokines. Understanding adipokine signaling in the brain and other organs will provide insights into the pathogenesis and treatment of obesity, diabetes and various metabolic disorders.
Mol Endocrinol 2008 May
PMID:Adipokines and the peripheral and neural control of energy balance. 1820 44

Adiponectin is an adipokine that has been implicated in insulin resistance, a condition associated with polycystic ovarian syndrome in humans, but whether adiponectin can directly affect ovarian theca or granulosa cell function is unknown. Therefore, to determine the effects of adiponectin on proliferation, steroidogenesis and gene expression of large-follicle theca and granulosa cells, experiments were conducted using bovine ovarian cell cultures. RT-PCR was used to elucidate the effects of adiponectin on gene expression of CYP11A1 and LH receptor (LHR) in large-follicle theca and granulosa cells, as well as expression of CYP17A1 in theca cells and CYP19A1 in granulosa cells. Adiponectin decreased (P<0.05) insulin-induced progesterone and androstenedione production as well as attenuated IGF-I-induced LHR, CYP11A1, and CYP17A1 gene expression in theca cells. In contrast, adiponectin decreased (P<0.05) LHR mRNA abundance in granulosa cells but did not affect steroidogenic enzyme gene expression in granulosa cells. Adiponectin had no effect (P>0.10) on proliferation of large-follicle theca cells. RT-PCR also revealed that abundance of mRNA for the adiponectin receptor (ADIPOR2) was greater (P<0.05) in large-follicle than in small-follicle theca cells and did not significantly differ between small- and large-follicle granulosa cells. In cultured theca cells, LH increased (P<0.05) and IGF-I decreased (P<0.05) ADIPOR2 mRNA abundance. These results indicate that the inhibitory effects of adiponectin on steroidogenesis are primarily localized to theca cells and that the response of theca cells to adiponectin (i.e., ADIPOR2) may be regulated by LH and IGF-I.
Mol Cell Endocrinol 2008 Mar 12
PMID:Role of adiponectin in regulating ovarian theca and granulosa cell function. 1828 73

Adipose tissue-derived cytokines (adipokines) are associated with the development of inflammation and insulin resistance. However, which adipokine(s) mediate this linkage and the mechanisms involved during obesity is poorly understood. Through proteomics and microarray screening, we recently identified lipocalin 2 (LCN 2) as an adipokine that potentially connects obesity and its related adipose inflammation. Herein we show that the levels of LCN2 mRNA are dramatically increased in adipose tissue and liver of ob/ob mice and primary adipose cells isolated from Zucker obese rats, and thiazolidinedione administration reduces LCN2 expression. Interestingly, addition of LCN2 induces mRNA levels of peroxisome proliferator-activated receptor-gamma (PPARgamma) and adiponectin. Reducing LCN2 gene expression causes decreased expression of PPARgamma and adiponectin, slightly reducing insulin-stimulated Akt2 phosphorylation at Serine 473 in 3T3-L1 adipocytes. LCN2 administration to 3T3-L1 cells attenuated TNFalpha-effect on glucose uptake, expression of PPARgamma, insulin receptor substrate-1, and glucose transporter 4, and secretion of adiponectin and leptin. When added to macrophages, LCN2 suppressed lipopolysaccharide-induced cytokine production. Our data suggest that LCN2, as a novel autocrine and paracrine adipokine, acts as an antagonist to the effect of inflammatory molecules on inflammation and secretion of adipokines.
Mol Endocrinol 2008 Jun
PMID:The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. 1829 40

Chronic ethanol consumption dysregulates glucose and lipid homeostasis, is associated with insulin resistance, and alters serum levels of adipokines including adiponectin and tumor necrosis factor-alpha. However, the mechanisms involved in these chronic ethanol-induced pathologies are not fully understood. Adipose tissue has been implicated as an important contributor to chronic ethanol-induced disease states and, therefore, the effects of chronic ethanol feeding in rats on adipocytes has been investigated. Three major functions of the adipocyte include glucose transport, adipokine secretion, and triglyceride breakdown via lipolysis. Included in this chapter are protocols for studying the effect of chronic ethanol feeding on these adipocyte functions.
Methods Mol Biol 2008
PMID:Methods to investigate the effects of chronic ethanol on adipocytes. 1836 29

Adipose tissue is a metabolically responsive endocrine organ that secretes a myriad of adipokines. Antidiabetic drugs such as peroxisome proliferator-activated receptor (PPAR) gamma agonists target adipose tissue gene expression and correct hyperglycemia via whole-body insulin sensitization. The mechanism by which altered gene expression in adipose tissue affects liver and muscle insulin sensitivity (and thus glucose homeostasis) is not fully understood. One possible mechanism involves the alteration in adipokine secretion, in particular the up-regulation of secreted factors that increase whole-body insulin sensitivity. Here, we report the use of transcriptional profiling to identify genes encoding for secreted proteins the expression of which is regulated by PPARgamma agonists. Of the 379 genes robustly regulated by two structurally distinct PPARgamma agonists in the epididymal white adipose tissue (EWAT) of db/db mice, 33 encoded for known secreted proteins, one of which was FGF21. Although FGF21 was recently reported to be up-regulated in cultured adipocytes by PPARgamma agonists and in liver by PPARalpha agonists and induction of ketotic states, we demonstrate that the protein is transcriptionally up-regulated in adipose tissue in vivo by PPARgamma agonist treatment and under a variety of physiological conditions, including fasting and high fat diet feeding. In addition, we found that circulating levels of FGF21 protein were increased upon treatment with PPARgamma agonists and under ketogenic states. These results suggest a role for FGF21 in mediating the antidiabetic activities of PPARgamma agonists.
Mol Pharmacol 2008 Aug
PMID:Adipose fibroblast growth factor 21 is up-regulated by peroxisome proliferator-activated receptor gamma and altered metabolic states. 1846 42

Brown and white adipose tissues in mammals have a number of similar properties, such as lipid storage and adipokine production, but also distinctive properties. The energy-storing white adipose tissue has few mitochondria and low oxidative capacity. The heat-producing brown adipose tissue has a high density of mitochondria and high oxidative capacity. Mitochondrial function can be investigated in cells and organelles isolated from both brown and white adipose tissues. This chapter describes methods for successful isolation of suitable preparations of adipose tissues and their subsequent use. Questions concerning thermogenic capacity of the tissues, their potential influence on whole body metabolism, and specific properties of the mitochondria and their mode of function may be addressed using these methods.
Methods Mol Biol 2008
PMID:Studies of thermogenesis and mitochondrial function in adipose tissues. 1851 56

Adipose tissue is increasingly recognized as a metabolically active endocrine organ with multiple functions beyond its lipid storage capability. Various constituents of the tissue, such as mature adipocytes and stromal vascular cells, have distinct functions. For example, they express and secrete different kinds of bioactive molecules collectively called adipokines. Altered adipokine secretion patterns characterize obesity and insulin resistance, which are major risk factors for type 2 diabetes mellitus. The contribution of dysregulated adipokine expression to these diseases may be assembled from transcriptomic profiles of the tissue and/or its cellular constituents. The gene expression profiles may also complement genetic approaches to identify disease susceptibility genes. Here, we describe an application of gene expression profiling using DNA microarrays to study human adipose tissue, adipocytes, and stromal vascular cells.
Methods Mol Biol 2008
PMID:Application of DNA microarray to the study of human adipose tissue/cells. 1851 59

Interleukin-1beta (IL-1beta) is a potent negative inotrope implicated in the functional abnormalities of heart failure. Because the adipokine, leptin, protects against some of the cardiovascular effects of endotoxin, we hypothesized that leptin may modulate the cardiosuppressive effects of IL-1beta in isolated cardiomyocytes. Ventricular cardiac myocytes isolated from adult male Sprague Dawley rats were analyzed simultaneously for electrically stimulated contractility and calcium transients following 30 min exposure to IL-1beta (10 ng/ml) with or without 60 min pretreatment with leptin (25 ng/ml). IL-1beta decreased cell shortening, depressed maximal velocities of shortening and relengthening, and prolonged the time to 90% relaxation. The change in fura2-AM fluorescence ratio amplitude (Delta[Ca(2+)]) was significantly depressed and the time to return to baseline [Ca(2+)] was prolonged. The negative inotropic effects of IL-1beta were blocked by the neutral sphingomyelinase inhibitor Manumycin A (5 microM) or the ceramidase inhibitor N-oleoyl ethanolamine (1 microM). Prior exposure of myocytes to leptin blocked IL-1beta-induced cardiosuppression in conjunction with a blunting of IL-1beta stimulated ceramide accumulation. These data suggest that leptin may modulate IL-1beta signaling through the sphingolipid signaling pathway in cardiomyocytes.
Mol Cell Biochem 2008 Aug
PMID:Leptin modulates the negative inotropic effect of interleukin-1beta in cardiac myocytes. 1853 86


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