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Yinuo Liu, Elke Albrecht, Lisa Schering, Christa Kuehn, Runjun Yang, Zhihui Zhao, Steffen Maak
Transcriptome analyses of bovine muscle tissue differing in intramuscular fat (IMF) content identified agouti signaling protein (ASIP) as a promising candidate gene for fat deposition. The protein is secreted from adipocytes and may serve as a signaling molecule in cross-talk between adipocytes and muscle fibers or other cells. Known receptors for ASIP are the melanocortin receptors (e.g., MC4R) and attractin (ATRN). The present study was conducted to determine relationships between the expression of ASIP and its receptors in different bovine tissues with fat deposition...
2018: Frontiers in Physiology
Ghazaul Dezfuli, Richard A Gillis, Jaclyn E Tatge, Kimbell R Duncan, Kenneth L Dretchen, Patrick G Jackson, Joseph G Verbalis, Niaz Sahibzada
Background/Objectives: We tested the hypothesis that abolishing vagal nerve activity will reverse the obesity phenotype of melanocortin 4 receptor knockout mice ( Mc4r -/- ). Subjects/Methods: In two separate studies, we examined the efficacy of bilateral subdiaphragmatic vagotomy (SDV) with pyloroplasty in the prevention and treatment of obesity in Mc4r -/- mice. Results: In the first study, SDV prevented >20% increase in body weight (BW) associated with this genotype. This was correlated with a transient reduction in overall food intake (FI) in the preventative arm of the study...
2018: Frontiers in Neuroscience
Robert M Dores, Michelle Scuba-Gray, Bridgette McNally, Perry Davis, Akiyoshi Takahashi
Previous studies on bony vertebrate MC2R orthologs (i.e., ray finned fishes, amphibians, reptiles, birds, and mammals) have shown that these MC2R orthologs have an obligatory requirement for interaction with bony vertebrate MRAP1 orthologs to a) allow for the trafficking of the MC2R ortholog to the plasma membrane; and b) to allow activation by ACTH, but not by any MSH-sized ligand. In addition, previous studies have found that co-expression of teleost and mammalian MC4R orthologs with corresponding MRAP2 has positive effects on sensitivity to stimulation by αMSH or ACTH...
March 7, 2018: General and Comparative Endocrinology
Anita H Clayton, Sheryl A Kingsberg, Irwin Goldstein
INTRODUCTION: Hypoactive sexual desire disorder (HSDD) often has a negative impact on the health and quality of life of women; however, many women do not mention-let alone discuss-this issue with their physicians. Providers of gynecologic services have the opportunity to address this subject with their patients. AIM: To review the diagnosis and evidence-based treatment of low sexual desire in women with a focus on strategies that can be used efficiently and effectively in the clinic...
March 6, 2018: Sexual Medicine
Ting Gong, Daniel J Torres, Marla J Berry, Matthew W Pitts
The hypothalamus is the central neural site governing food intake and energy expenditure. During the past 25 years, understanding of the hypothalamic cell types, hormones, and circuitry involved in the regulation of energy metabolism has dramatically increased. It is now well established that the adipocyte-derived hormone, leptin, acts upon two distinct groups of hypothalamic neurons that comprise opposing arms of the central melanocortin system. These two cell populations are anorexigenic neurons expressing proopiomelanocortin (POMC) and orexigenic neurons that express agouti-related peptide (AGRP)...
March 5, 2018: Free Radical Biology & Medicine
Luis Varela, Tamas L Horvath
Melanocortin receptors play crucial roles in multiple physiological processes. Melanocortin receptor 4 (MC4R) is expressed in key brain regions, and MC4R gene mutations can cause severe obesity. However, the cellular biology of MC4R is less well understood owing to the lack of reliable methods to visualize its location. Recently, Siljee and colleagues localized MC4R to the cilia of the neurons within the hypothalamus and showed that cilial expression of MC4R is crucial for the control of metabolic phenotype...
February 28, 2018: Trends in Molecular Medicine
Juliana Pereira Lopes Gonçalves, Daniel Palmer, Morten Meldal
The melanocortin-4 receptor (MC4R) regulates adipose tissue formation and energy homeostasis, and is believed to be a monogenic target for novel antiobesity therapeutics. Several research efforts targeting this receptor have identified potent and selective agonists. While viable agonists have been characterized in vitro, undesirable side effects frequently appeared during clinical trials. The most promising candidates have diverse structures, including linear peptides, cyclic peptides, and small molecules. Herein, we present a compilation of potent MC4R agonists and discuss the pivotal structural differences within those molecules that resulted in good selectivity for MC4R over other melanocortins...
February 22, 2018: Trends in Pharmacological Sciences
Iain R Tough, Sarah Forbes, Herbert Herzog, Robert M Jones, Thue W Schwartz, Helen M Cox
The lipid sensor GPR119 is highly expressed by enteroendocrine L-cells and pancreatic β-cells that release the hormones, PYY and GLP-1, and insulin, respectively. Endogenous oleoylethanolamide (OEA) and the dietary metabolite, 2-monoacylglycerol (2-OG) can each activate GPR119. Here we compared mucosal responses to selective, synthetic GPR119 agonists (AR440006, AR231453) and the lipids, OEA, 2-OG and N-oleoyldopamine (OLDA) monitoring epithelial ion transport as a read-out for L-cell activity in native mouse and human gastrointestinal (GI) mucosae...
February 19, 2018: Endocrinology
Cyril Cyrus, Mona H Ismail, Shahanas Chathoth, Chittibabu Vatte, Majd Hasen, Amein Al Ali
BACKGROUND: Obesity has reached epidemic proportions worldwide resulting in a serious public health problem. In Saudi Arabia, 28.7% of the population is obese due largely to the adoption of western dietary patterns over the last decade. The Fat-mass and obesity associated (FTO) and melanocortin-4 receptor (MC4R) genes are ubiquitously expressed in the brain and pancreatic islets, and are the main link between the central nervous system and energy homeostasis based on food intake and energy expenditure...
February 21, 2018: Genetic Testing and Molecular Biomarkers
Giuseppe Bruschetta, Sungho Jin, Jung Dae Kim, Sabrina Diano
OBJECTIVE: Prolyl carboxypeptidase (PRCP) plays a role in the regulation of energy metabolism by inactivating hypothalamic α-melanocyte stimulating hormone (α-MSH) levels. Although detected in the arcuate nucleus, limited PRCP expression has been observed in the arcuate POMC neurons, and its site of action in regulating metabolism is still ill-defined. METHODS: We performed immunostaining to assess the localization of PRCP in arcuate Neuropeptide Y/Agouti-related Peptide (NPY/AgRP) neurons...
February 8, 2018: Molecular Metabolism
Andrea Mastinu, Marika Premoli, Giuseppina Maccarinelli, Mariagrazia Grilli, Maurizio Memo, Sara Anna Bonini
Several studies on humans and mice support oxytocin's role in improving social behaviour, but its use in pharmacotherapy presents some important limiting factors. To date, it is emerging a pharmacological potential for melanocortin 4 receptor (MC4R) agonism in social deficits treatment. Recently, we demonstrated that the deletion of the NFKB1 gene, which encodes the p50 NF-κB subunit, causes impairment in social behaviours, with reductions in social interactions in mice. In this work, we tested the acute effects of THIQ, a selective melanocortin 4 receptor (MC4R) agonist...
February 15, 2018: Neuropharmacology
Norimichi Chiyonobu, Shu Shimada, Yoshimitsu Akiyama, Kaoru Mogushi, Michiko Itoh, Keiichi Akahoshi, Satoshi Matsumura, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Daisuke Ban, Atsushi Kudo, Shigeki Arii, Takayoshi Suganami, Shoji Yamaoka, Yoshihiro Ogawa, Minoru Tanabe, Shinji Tanaka
Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma (HCC); however, tumor-specific biomarkers still remain unclear. We performed cross-species analysis to compare gene signatures of HCC from human patients and melanocortin 4 receptor-knockout (MC4R-KO) mice, which develop HCC with obesity, insulin resistance, and dyslipidemia. Unsupervised hierarchical clustering and principle component analysis of 746 differentially expressed orthologous genes classified HCC of 152 human patients and MC4R-KO mice into two distinct subgroups, one of which included mouse HCC and was etiologically associated with metabolic risk factors...
February 15, 2018: American Journal of Pathology
Aygul Subkhangulova, Anna R Malik, Guido Hermey, Oliver Popp, Gunnar Dittmar, Thomas Rathjen, Matthew N Poy, Alexander Stumpf, Prateep Sanker Beed, Dietmar Schmitz, Tilman Breiderhoff, Thomas E Willnow
SORCS1 and SORCS3 are two related sorting receptors expressed in neurons of the arcuate nucleus of the hypothalamus. Using mouse models with individual or dual receptor deficiencies, we document a previously unknown function of these receptors in central control of metabolism. Specifically, SORCS1 and SORCS3 act as intracellular trafficking receptors for tropomyosin-related kinase B to attenuate signaling by brain-derived neurotrophic factor, a potent regulator of energy homeostasis. Loss of the joint action of SORCS1 and SORCS3 in mutant mice results in excessive production of the orexigenic neuropeptide agouti-related peptide and in a state of chronic energy excess characterized by enhanced food intake, decreased locomotor activity, diminished usage of lipids as metabolic fuel, and increased adiposity, albeit at overall reduced body weight...
February 12, 2018: EMBO Reports
Miguel López
No abstract text is available yet for this article.
February 2018: Molecular Metabolism
Markella Katidou, Xavier Grosmaitre, Jiangwei Lin, Peter Mombaerts
In the mouse, most mature olfactory sensory neurons (OSNs) express one allele of one gene from the repertoire of ~1100 odorant receptor (OR) genes, which encode G-protein coupled receptors (GPCRs). Axons of OSNs that express a given OR coalesce into homogeneous glomeruli, which reside at conserved positions in the olfactory bulb. ORs are intimately involved in ensuring the expression of one OR per OSN and the coalescence of OSN axons into glomeruli. But the mechanisms whereby ORs accomplish these diverse functions remain poorly understood...
January 30, 2018: Molecular and Cellular Neurosciences
Kumiko Shiba, Kyoichiro Tsuchiya, Chikara Komiya, Yasutaka Miyachi, Kentaro Mori, Noriko Shimazu, Shinobu Yamaguchi, Naomi Ogasawara, Makoto Katoh, Michiko Itoh, Takayoshi Suganami, Yoshihiro Ogawa
Sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. It is unclear whether SGLT2 inhibition could attenuate nonalcoholic steatohepatitis (NASH) and NASH-associated hepatocellular carcinoma. We examined the preventive effects of an SGLT2 inhibitor canagliflozin (CANA) in Western diet (WD)-fed melanocortin 4 receptor-deficient (MC4R-KO) mice, a mouse model of human NASH. An eight-week CANA treatment attenuated hepatic steatosis in WD-fed MC4R-KO mice, with increased epididymal fat mass without inflammatory changes...
February 5, 2018: Scientific Reports
Siwei Cai, Qianhui Yang, Mengzhu Hou, Qian Han, Hanyu Zhang, Jiantao Wang, Chen Qi, Qiyu Bo, Yusha Ru, Wei Yang, Zhongxiu Gu, Ruihua Wei, Yunshan Cao, Xiaorong Li, Yan Zhang
BACKGROUND/AIMS: Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A)...
January 25, 2018: Cellular Physiology and Biochemistry
Jae Ok Seo, Silvia Yumnam, Kwang Won Jeong, Sun Yeou Kim
Finasteride is a well-known 5α-reductase inhibitor used for treatment of alopecia and prostate cancer. But the effect of finasteride in regulating melanogenesis is still unclear. In the present study the role of finasteride on melanogenesis was investigated. Finasteride decrease melanin level in melanocyte melan-a cells and B16F10 melanoma cells without inducing cytotoxicity. MC1R (melanocortin 1 receptor) protein expression was also inhibited by finasteride thereby decreasing the expression of adenylate cyclase, MITF (Melanogenesis associated transcription factor), tyrosinases, TRP (tyrosinase-related protein) -1 and -2...
February 3, 2018: Archives of Pharmacal Research
Irina V Romanova, Kira V Derkach, Anastasiya L Mikhrina, Ivan B Sukhov, Elena V Mikhailova, Alexander O Shpakov
The pro-opiomelanocortin (POMC)-expressing neurons of the hypothalamic arcuate nucleus (ARC) are involved in the control of food intake and metabolic processes. It is assumed that, in addition to leptin, the activity of these neurons is regulated by serotonin and dopamine, but only subtype 2C serotonin receptors (5-HT2CR) was identified earlier on the POMC-neurons. The aim of this work was a comparative study of the localization and number of leptin receptors (LepR), types 1 and 2 dopamine receptors (D1R, D2R), 5-HT1BR and 5-HT2CR on the POMC-neurons and the expression of the genes encoding them in the ARC of the normal and diet-induced obese (DIO) rodents and the agouti mice (A y /a) with the melanocortin obesity...
February 3, 2018: Neurochemical Research
Gwyndolin Vail, Troy A Roepke
The last few decades have revealed increasing complexity and depth to our knowledge of receptor-mediated estrogen signaling. Nuclear estrogen receptors (ERs) ERα and ERβ remain the fundamental dogma, but developing research targeting membrane-bound ERs urges for a more expanded view on ER signaling. ERα and ERβ are also involved in membrane-delineated signaling alongside membrane-specific G protein-coupled estrogen receptor 1 (GPER1), ER-X, and the Gq-coupled membrane ER (Gq-mER). Membrane ERs are responsible for eliciting rapid responses to estrogen signaling, and their importance has been increasingly indicated in central nervous system (CNS) regulation of such functions as reproduction, energy homeostasis, and stress...
January 26, 2018: Steroids
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