Neuropeptide AF and FF Modulation of Adipocyte Metabolism

Lefrère, Isabelle; Coppet, Pierre de; Camelin, Jean-Claude; Lay, Soazig Le; Mercier, Nathalie; Elshourbagy, Nabil A.; Bril, Antoine; Berrebi-Bertrand, Isabelle; Fève, Bruno; Krief, Stéphane

doi:10.1074/jbc.m205084200

Cited by 34 publications

(10 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clarke [29], Cu–Zn SOD (SOD1) was from the American Type Tissue Collection, and a 1,257 bp fragment of the murine COX-1 (PTGS1) was synthesized using 5′-TTCCTGATTCAAAAGAAGTTCTGG-3′ as the forward primer and 5′-ATGGTGGCTGTTTTGGTAGGCTGT-3′ as the reverse primer on reverse transcribed RNA isolated from murine liver using published methodology [30]. Hepatic FADS2 (Δ-6 desaturase) and SCD 1 mRNA levels were assessed by quantitative real time PCR using published primers [31, 32], respectively) and mouse specific primers for COX-2 (PTGS2, NM_011198.3) were designed using the NCBI Primer-blast tool: forward 5′-G GCTGTTGGAATTTACGCAT-3′ and reverse 5′-CAGG GCCTTCAAAATGTCTA-3′. The internal endogenous control was GAPDH and used published primers [33].…”

Section: Methodsmentioning

confidence: 99%

Growth Hormone Enhances Arachidonic Acid Metabolites in a Growth Hormone Transgenic Mouse

Oberbauer

German

Murray

2011

Lipids

View full text Add to dashboard Cite

In a transgenic growth hormone (GH) mouse model, highly elevated GH increases overall growth and decreases adipose depots while low or moderate circulating GH enhances adipose deposition with differential effects on body growth. Using this model, the effects of low, moderate, and high chronic GH on fatty acid composition were determined for adipose and hepatic tissue and the metabolites of 20:4n-6 (arachidonic acid) were characterized to identify metabolic targets of action of elevated GH. The products of Δ-9 desaturase in hepatic, but not adipose, tissue were reduced in response to elevated GH. Proportional to the level of circulating GH, the products of Δ-5 and Δ-6 were increased in both adipose and hepatic tissue for the omega-6 lipids (e.g., 20:4n-6), while only the hepatic tissues showed an increase for omega-3 lipids (e.g., 22:6n-3). The eicosanoids, PGE2 and 12-HETE, were elevated with high GH but circulating thromboxane was not. Hepatic PTGS1 and 2 (COX1 and COX 2), SOD1, and FADS2 (Δ-6 desaturase) mRNAs were increased with elevated GH while FAS mRNA was reduced; SCD1 (ste-aroyl-coenzyme A desaturase) and SCD2 mRNA did not significantly differ. The present study showed that GH influences the net flux through various aspects of lipid metabolism and especially the desaturase metabolic processes. The combination of altered metabolism and tissue specificity suggest that the regulation of membrane composition and its effects on signaling pathways, including the production and actions of eicosanoids, can be mediated by the GH regulatory axis.

show abstract

Section: Methodsmentioning

confidence: 99%

Growth Hormone Enhances Arachidonic Acid Metabolites in a Growth Hormone Transgenic Mouse

Oberbauer

German

Murray

2011

Lipids

View full text Add to dashboard Cite

show abstract

“…3T3-L1 adipocytes express three subtypes of ␤-adrenergic receptors (29), and the ␤ 3 -adrenergic receptor has been found to be dramatically increased (30) after differentiation. Several mechanisms have been proposed by which ␤-adrenergic receptor stimulation may affect insulin-stimulated glucose uptake in 3T3-L1 and rat adipocytes (12,(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

New Insights into Cytosolic Glucose Levels during Differentiation of 3T3-L1 Fibroblasts into Adipocytes

Kovačič

Chowdhury

Velebit

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cytosolic glucose concentration reflects the balance between glucose entry across the plasma membrane and cytosolic glucose utilization. In adipocytes, glucose utilization is considered very rapid, meaning that every glucose molecule entering the cytoplasm is quickly phosphorylated. Thus, the cytosolic free glucose concentration is considered to be negligible; however, it was never measured directly. In the present study, we monitored cytosolic glucose dynamics in 3T3-L1 fibroblasts and adipocytes by expressing a fluorescence resonance energy transfer (FRET)-based glucose nanosensor: fluorescent indicator protein FLIPglu-600. Specifically, we monitored cytosolic glucose responses by varying transmembrane glucose concentration gradient. The changes in cytosolic glucose concentration were detected in only 56% of 3T3-L1 fibroblasts and in 14% of 3T3-L1 adipocytes. In adipocytes, the resting cytosolic glucose concentration was reduced in comparison with the one recorded in fibroblasts. Membrane permeabilization increased cytosolic glucose concentration in adipocytes, and glycolytic inhibitor iodoacetate failed to increase cytosolic glucose concentration, indicating low adipocyte permeability for glucose at rest. We also examined the effects of insulin and adrenaline. Insulin significantly increased cytosolic glucose concentration in adipocytes by a factor of 3.6; however, we recorded no effect on delta ratio (⌬R) in fibroblasts. Adrenaline increased cytosolic glucose concentration in fibroblasts but not in adipocytes. However, in adipocytes in insulin-stimulated conditions, glucose clearance was significantly faster following adrenaline addition in comparison with controls (p < 0.001). Together, these results demonstrate that during differentiation, adipocytes develop more efficient mechanisms for maintaining low cytosolic glucose concentration, predominantly with reduced membrane permeability for glucose.Adipocytes utilize glucose to supply energy needs for cellular activities and to promote synthesis and storage of lipids in the cell. Glucose utilization is regulated by the supply of intracellular glucose-6-phosphate. This, in turn, depends on the transport of glucose across the cell membrane and its phosphorylation in the presence of hexokinase and ATP. Adipocytes contain two isoforms of a family of proteins that facilitate transport of glucose across the plasma membrane: GLUT1, the constitutive glucose transporter located mainly at the plasma membrane, and GLUT4, the insulin-sensitive glucose transporter (1, 2). The effect of insulin to increase glucose uptake is exerted by stimulating the translocation of GLUT4 from an intracellular pool to the plasma membrane and thus increasing the permeability of the plasma membrane to glucose (3, 4). However, the accompanying changes in dynamics of intracellular glucose concentration in a single adipocyte are not known as, until recently, it was not possible to measure this parameter directly. To image and quantify changes in cytosolic glucose, Fehr et al. (6) constructed a...

show abstract

“…NPFF and NPAF have long been recognized for their pain modulatory effects, in particular for their fundamental role in opioid analgesia and tolerance development (for review see [35,36]). In addition, a panel of other physiological processes, such as modulation of food intake in rats [37,38], insulin release [38] as well as adipocyte metabolism [39] and somatostatin secretion from the pancreas [40], has also been reported. Furthermore, effects on arterial blood pressure [41,42] and heart rate were described [42,43].…”

Section: Two Homologous Rf-amide Precursors: Pro-npffa and Pro-npffbmentioning

confidence: 98%

Discovery of Novel Regulatory Peptides by Reverse Pharmacology: Spotlight on Chemerin and the RF-amide Peptides Metastin and QRFP

Kutzleb¹,

Busmann²,

Wendland³

et al. 2005

CPPS

View full text Add to dashboard Cite

Reverse pharmacology is a screening technology that matches G protein-coupled receptors (GPCRs) with unknown cognate ligands in cell-based screening assays by detection of agonist-induced signaling pathways. One decade spent pursuing orphan GPCR screening by this technique assigned over 30 ligand/receptor pairs and revealed previously known or novel undescribed ligands, mostly of a peptidic nature. In this review, we describe the discovery, characterization of the structural composition, biological function, physiological role and therapeutic potential of three recently identified peptidic ligands. These are metastin, QRFP in a context of five RF-amide genes described in humans and the chemoattractant, chemerin. Metastin was initially characterized as a metastasis inhibitor. Investigations using ligand/receptor pairing revealed that metastin was involved in a variety of physiological processes, including endocrine function during pregnancy and gonad development. The novel RF-amide QRFP is implicated in food intake and aldosterone release from the adrenal cortex in the rat. Chemerin, first described as TIG2, is upregulated in tazarotene-treated psoriatic skin. By GPCR screening, bioactive chemerin was isolated from ovarial carcinoma fluid as well as hemofiltrate. Characterization as a chemoattractant for immature dendritic cells and analysis of the expression profile of metastin and its receptor suggested a physiological role of chemerin as a mediator of the immune response, inflammatory processes and bone development.

show abstract

Neuropeptide AF and FF Modulation of Adipocyte Metabolism

Cited by 34 publications

References 50 publications

Growth Hormone Enhances Arachidonic Acid Metabolites in a Growth Hormone Transgenic Mouse

Growth Hormone Enhances Arachidonic Acid Metabolites in a Growth Hormone Transgenic Mouse

New Insights into Cytosolic Glucose Levels during Differentiation of 3T3-L1 Fibroblasts into Adipocytes

Discovery of Novel Regulatory Peptides by Reverse Pharmacology: Spotlight on Chemerin and the RF-amide Peptides Metastin and QRFP

Contact Info

Product

Resources

About