scholarly journals The role of the central melanocortin system in the regulation of food intake and energy homeostasis: lessons from mouse models

2006 ◽  
Vol 361 (1471) ◽  
pp. 1265-1274 ◽  
Author(s):  
Kate L.J Ellacott ◽  
Roger D Cone

A little more than a decade ago, the molecular basis of the lipostat was largely unknown. At that time, many laboratories were at work attempting to clone the genes encoding the obesity , diabetes , fatty , tubby and agouti loci, with the hope that identification of these obesity genes would help shed light on the process of energy homeostasis, appetite and energy expenditure. Characterization of obesity and diabetes elucidated the nature of the adipostatic hormone leptin and its receptor, respectively, while cloning of the agouti gene eventually led to the identification and characterization of one of the key neural systems upon which leptin acts to regulate intake and expenditure. In this review, we describe the neural circuitry known as the central melanocortin system and discuss the current understanding of its role in feeding and other processes involved in energy homeostasis.

2009 ◽  
Vol 284 (24) ◽  
pp. 16513-16521 ◽  
Author(s):  
Kenta Tsunekawa ◽  
Toshiaki Shijuku ◽  
Mitsuo Hayashimoto ◽  
Yoichi Kojima ◽  
Kiyoshi Onai ◽  
...  

Na+/H+ antiporters influence proton or sodium motive force across the membrane. Synechocystis sp. PCC 6803 has six genes encoding Na+/H+ antiporters, nhaS1–5 and sll0556. In this study, the function of NhaS3 was examined. NhaS3 was essential for growth of Synechocystis, and loss of nhaS3 was not complemented by expression of the Escherichia coli Na+/H+ antiporter NhaA. Membrane fractionation followed by immunoblotting as well as immunogold labeling revealed that NhaS3 was localized in the thylakoid membrane of Synechocystis. NhaS3 was shown to be functional over a pH range from pH 6.5 to 9.0 when expressed in E. coli. A reduction in the copy number of nhaS3 in the Synechocystis genome rendered the cells more sensitive to high Na+ concentrations. NhaS3 had no K+/H+ exchange activity itself but enhanced K+ uptake from the medium when expressed in an E. coli potassium uptake mutant. Expression of nhaS3 increased after shifting from low CO2 to high CO2 conditions. Expression of nhaS3 was also found to be controlled by the circadian rhythm. Gene expression peaked at the beginning of subjective night. This coincided with the time of the lowest rate of CO2 consumption caused by the ceasing of O2-evolving photosynthesis. This is the first report of a Na+/H+ antiporter localized in thylakoid membrane. Our results suggested a role of NhaS3 in the maintenance of ion homeostasis of H+, Na+, and K+ in supporting the conversion of photosynthetic products and in the supply of energy in the dark.


2003 ◽  
Vol 284 (3) ◽  
pp. E468-E474 ◽  
Author(s):  
Ira Gantz ◽  
Tung M. Fong

The melanocortin system consists of melanocortin peptides derived from the proopiomelanocortin gene, five melanocortin receptors, two endogenous antagonists, and two ancillary proteins. This review provides an abbreviated account of the basic biochemistry, pharmacology, and physiology of the melanocortin system and highlights progress made in four areas. In particular, recent pharmacological and genetic studies have affirmed the role of melanocortins in pigmentation, inflammation, energy homeostasis, and sexual function. Development of selective agonists and antagonists is expected to further facilitate the investigation of these complex physiological functions and provide an experimental basis for new pharmacotherapies.


2015 ◽  
Vol 59 (9) ◽  
pp. 5357-5365 ◽  
Author(s):  
Hilde Smith ◽  
Alex Bossers ◽  
Frank Harders ◽  
Guanghui Wu ◽  
Neil Woodford ◽  
...  

ABSTRACTThe aim of the study was to identify the plasmid-encoded factors contributing to the emergence and spread of epidemic IncI1-Iγ plasmids obtained fromEscherichia coliandSalmonella entericaisolates from animal and human reservoirs. For this, 251 IncI1-Iγ plasmids carrying various extended-spectrum β-lactamase (ESBL) or AmpC β-lactamase genes were compared using plasmid multilocus sequence typing (pMLST). Thirty-two of these plasmids belonging to different pMLST types were sequenced using Roche 454 and Illumina platforms. Epidemic IncI1-Iγ plasmids could be assigned to various dominant clades, whereas rarely detected plasmids clustered together as a distinct clade. Similar phylogenetic trees were obtained using only the plasmid backbone sequences, showing that the differences observed between the plasmids belonging to distinct clades resulted mainly from differences between their backbone sequences. Plasmids belonging to the various clades differed particularly in the presence/absence of genes encoding partitioning and addiction systems, which contribute to stable inheritance during cell division and plasmid maintenance. Despite this, plasmids belonging to the various phylogenetic clades also showed marked resistance gene associations, indicating the circulation of successful plasmid-gene combinations. The variation intraYandexcAgenes found in IncI1-Iγ plasmids is conserved within pMLST sequence types and plays a role in incompatibility, although functional study is needed to elucidate the role of these genes in plasmid epidemiology.


Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 483
Author(s):  
Tomohiro Morohoshi ◽  
Yaoki Kamimura ◽  
Nobutaka Someya

N-Acylhomoserine lactones (AHLs) are used as quorum-sensing signals in Gram-negative bacteria. Many genes encoding AHL-degrading enzymes have been cloned and characterized in various microorganisms. Coagulase-negative staphylococci (CNS) are present on the skin of animals and are considered low-virulent species. The AHL-lactonase gene homologue, ahlS, was present in the genomes of the CNS strains Staphylococcus carnosus, Staphylococcus haemolyticus, Staphylococcus saprophyticus, and Staphylococcus sciuri. We cloned the candidate ahlS homologue from six CNS strains into the pBBR1MCS5 vector. AhlS from the CNS strains showed a higher degrading activity against AHLs with short acyl chains compared to those with long acyl chains. AhlS from S. sciuri was expressed and purified as a maltose-binding protein (MBP) fusion. Pseudomonas aeruginosa is an opportunistic pathogen that regulates several virulence factors such as elastase and pyocyanin by quorum-sensing systems. When MBP-AhlS was added to the culture of P. aeruginosa PAO1, pyocyanin production and elastase activity were substantially reduced compared to those in untreated PAO1. These results demonstrate that the AHL-degrading activity of AhlS from the CNS strains can inhibit quorum sensing in P. aeruginosa PAO1.


2010 ◽  
Vol 97 (1) ◽  
pp. S70-S71
Author(s):  
Busser Benoît ◽  
Lucie Sancey ◽  
Véronique Josserand ◽  
Saadi Khochbin ◽  
Jean-Luc Coll ◽  
...  

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3707-3718 ◽  
Author(s):  
J.B. Singer ◽  
R. Harbecke ◽  
T. Kusch ◽  
R. Reuter ◽  
J.A. Lengyel

Chromosomal region 68D/E is required for various aspects of Drosophila gut development; within this region maps the Brachyury homolog T-related gene (Trg), DNA of which rescues the hindgut defects of deficiency 68D/E. From a screen of 13,000 mutagenized chromosomes we identified six non-complementing alleles that are lethal over deficiencies of 68D/E and show a hindgut phenotype. These mutations constitute an allelic series and are all rescued to viability by a Trg transgene. We have named the mutant alleles and the genetic locus they define brachyenteron (byn); phenotypic characterization of the strongest alleles allows determination of the role of byn in embryogenesis. byn expression is activated by tailless, but byn does not regulate itself. byn expression in the hindgut and anal pad primordia is required for the regulation of genes encoding transcription factors (even-skipped, engrailed, caudal, AbdominalB and orthopedia) and cell signaling molecules (wingless and decapentaplegic). In byn mutant embryos, the defective program of gene activity in these primordia is followed by apoptosis (initiated by reaper expression and completed by macrophage engulfment), resulting in severely reduced hindgut and anal pads. Although byn is not expressed in the midgut or the Malpighian tubules, it is required for the formation of midgut constrictions and for the elongation of the Malpighian tubules.


2019 ◽  
Vol 20 (10) ◽  
pp. 2394 ◽  
Author(s):  
Minerva Mata-Rocha ◽  
Angelica Rangel-López ◽  
Elva Jiménez-Hernández ◽  
Blanca Angélica Morales-Castillo ◽  
Carolina González-Torres ◽  
...  

Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B, DNAH14-IKZF1, ETV6-SNUPN, ETV6-NUFIP1. Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1, CREBBP, and ETV6. In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.


2006 ◽  
Vol 50 (6) ◽  
pp. 1973-1981 ◽  
Author(s):  
Magdalena Stoczko ◽  
Jean-Marie Frère ◽  
Gian Maria Rossolini ◽  
Jean-Denis Docquier

ABSTRACT The diffusion of metallo-β-lactamases (MBLs) among clinically important human pathogens represents a therapeutic issue of increasing importance. However, the origin of these resistance determinants is largely unknown, although an important number of proteins belonging to the MBL superfamily have been identified in microbial genomes. In this work, we analyzed the distribution and function of genes encoding MBL-like proteins in the class Rhizobiales. Among 12 released complete genomes of members of the class Rhizobiales, a total of 57 open reading frames (ORFs) were found to have the MBL conserved motif and identity scores with MBLs ranging from 8 to 40%. On the basis of the best identity scores with known MBLs, four ORFs were cloned into Escherichia coli for heterologous expression. Among their products, one (blr6230) encoded by the Bradyrhizobium japonicum USDA110 genome, named BJP-1, hydrolyzed β-lactams when expressed in E. coli. BJP-1 enzyme is most closely related to the CAU-1 enzyme from Caulobacter vibrioides (40% amino acid sequence identity), a member of subclass B3 MBLs. A kinetic analysis revealed that BJP-1 efficiently hydrolyzed most β-lactam substrates, except aztreonam, ticarcillin, and temocillin, with the highest catalytic efficiency measured with meropenem. Compared to other MBLs, BJP-1 was less sensitive to inactivation by chelating agents.


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