Leptin and Insulin Act on POMC Neurons to Promote the Browning of White Fat

SummaryThe primary task of white adipose tissue (WAT) is the storage of lipids. However, “beige” adipocytes also exist in WAT. Beige adipocytes burn fat and dissipate the energy as heat, but their abundance is diminished in obesity. Stimulating beige adipocyte development, or WAT browning, increases energy expenditure and holds potential for combating metabolic disease and obesity. Here, we report that insulin and leptin act together on hypothalamic neurons to promote WAT browning and weight loss. Deletion of the phosphatases PTP1B and TCPTP enhanced insulin and leptin signaling in proopiomelanocortin neurons and prevented diet-induced obesity by increasing WAT browning and energy expenditure. The coinfusion of insulin plus leptin into the CNS or the activation of proopiomelanocortin neurons also increased WAT browning and decreased adiposity. Our findings identify a homeostatic mechanism for coordinating the status of energy stores, as relayed by insulin and leptin, with the central control of WAT browning

Reduced Food Intake and Body Weight in Mice Deficient for the G Protein-Coupled Receptor GPR82

G protein-coupled receptors (GPCR) are involved in the regulation of numerous physiological functions. Therefore, GPCR variants may have conferred important selective advantages during periods of human evolution. Indeed, several genomic loci with signatures of recent selection in humans contain GPCR genes among them the X-chromosomally located gene for GPR82. This gene encodes a so-called orphan GPCR with unknown function. To address the functional relevance of GPR82 gene-deficient mice were characterized. GPR82-deficient mice were viable, reproduced normally, and showed no gross anatomical abnormalities. However, GPR82-deficient mice have a reduced body weight and body fat content associated with a lower food intake. Moreover, GPR82-deficient mice showed decreased serum triacylglyceride levels, increased insulin sensitivity and glucose tolerance, most pronounced under Western diet. Because there were no differences in respiratory and metabolic rates between wild-type and GPR82-deficient mice our data suggest that GPR82 function influences food intake and, therefore, energy and body weight balance. GPR82 may represent a thrifty gene most probably representing an advantage during human expansion into new environments

Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.ClinicalTrials.gov NCT00730509

L'objet - Groupe - Famille

Caillot J. P., Decherf G., Decobert S. L'objet - Groupe - Famille. In: Bulletin de psychologie, tome 37 n°363, 1983. Théorie psychanalytique des groupes. pp. 35-42

COMPARING IMAGE-BASED METHODS FOR ASSESSING VISUAL CLUTTER IN GENERALIZED MAPS

Map generalization abstracts and simplifies geographic information to derive maps at smaller scales. The automation of map generalization requires techniques to evaluate the global quality of a generalized map. The quality and legibility of a generalized map is related to the complexity of the map, or the amount of clutter in the map, i.e. the excessive amount of information and its disorganization. Computer vision research is highly interested in measuring clutter in images, and this paper proposes to compare some of the existing techniques from computer vision, applied to generalized maps evaluation. Four techniques from the literature are described and tested on a large set of maps, generalized at different scales: edge density, subband entropy, quad tree complexity, and segmentation clutter. The results are analyzed against several criteria related to generalized maps, the identification of cluttered areas, the preservation of the global amount of information, the handling of occlusions and overlaps, foreground vs background, and blank space reduction

Identification of phosphorylated proteins in erythrocytes infected by the human malaria parasite Plasmodium falciparum

Background: Previous comparative proteomic analysis on Plasmodium falciparum isolates of different adhesion properties suggested that protein phosphorylation varies between isolates with different cytoadherence properties. But the extent and dynamic changes in phosphorylation have not been systematically studied. As a baseline for these future studies, this paper examined changes in the phosphoproteome of parasitized red blood cells (pRBC). Methods: Metabolic labelling with [S-35] methionine on pRBC and 2D gel electrophoresis (2-DE) has previously been used to show the expression of parasite proteins and changes in protein iso-electric point (PI). 2-DE of different parasite strains was combined with immunoblotting using monoclonal antibodies specifically to phosphorylated serine/threonine and tyrosine, to obtain the phosphorylation profiles throughout the erythrocytic lifecycle. Affinity chromatography was used to purify/enrich phosphorylated proteins and these proteins from mature trophozoite stages which were identified using high-accuracy mass spectrometry and MASCOT search. Results: 2D-immunoblots showed that P. falciparum infection greatly increased phosphorylation of a set of proteins in pRBC, the dominant size classes for phosphorylated tyrosine proteins were 95, 60, 50 and 30 kDa and for phosphorylated serine/threonine were 120, 95, 60, 50, 43, 40 and 30 kDa. The most abundant molecules from 2D-gel mapping of phosphorylated proteins in ItG infected RBCs were identified by MALDI-TOF. A proteomic overview of phosphorylated proteins in pRBC was achieved by using complementary phosphorylated protein enrichment techniques combined with nano-flow LC/MS/MS analysis and MASCOT MS/MS ions search with phosphorylation as variable modifications. The definite phosphoproteins of pRBC are reported and discussed. Conclusion: Protein phosphorylation is a major process in P. falciparum-parasitized erythrocytes. Preliminary screens identified 170 P. falciparum proteins and 77 human proteins as phosphorylated protein in pRBC, while only 48 human proteins were identified in the corresponding fractions from uninfected RBC. Refinement of the search to include significant ion scores indicating a specific phospho-peptide identified 21 P. falciparum proteins and 14 human proteins from pRBC, 13 host proteins were identified from normal RBC. The results achieved by complementary techniques consistently reflect a reliable proteomic overview of pRBC

Cystic fibrosis as a bowel cancer syndrome and the potential role of CK2

Chloride is critical in creating differential pH values inside various organelles (Golgi for example) by linking ATP hydrolysis to trans-bilayer proton movement. This proton-ATPase drives anions such as chloride through unrelated channels in the endosomal/organellar bilayer thus loading HCl into different lipid-encased cellular compartments. Critically, intraorganellar pH (and ion channel content/activities) differs during different phases of the cell cycle. The cystic fibrosis (CF) chloride channel protein CFTR is a member of the ABC family (ABCC7) and resides in many endosomal membranes trafficking to the epithelial surface and back again. Recently, it has become clear that human CF has an unusually high incidence of cancer in the bowel with correspondingly elevated gut epithelial proliferation rates observed in CF mice. In this review, emphasis is placed on CK2 & CF because CK2 controls not only proliferation but also four different members of the ABC superfamily including the multi-drug resistance protein P-glycoprotein and CFTR itself. In addition, CK2 also regulates a critical cancer-relevant and CFTR-regulated cation channel (ENaC) that mediates the cellular accumulation of sodium ions within epithelia such as the colon and lung. Not only are ENaC and CFTR both abnormal in CF cells, but ENaC also ‘carries’ CK2 to the cell membrane in oocytes, only provided its two target phosphosites are intact. CK2 may be a critical regulator of cell proliferation in conjunction with regulation of ion channels such as CFTR, other ABC members and the cation channel ENaC. The emerging idea is that CFTR may control membrane-CK2 as much as membrane-CK2 controls CFTR