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https://www.readbyqxmd.com/read/29352962/improved-systemic-metabolism-and-adipocyte-biology-in-mir-150-knockout-mice
#1
Minsung Kang, Xiaobing Liu, Yuchang Fu, W Timothy Garvey
INTRODUCTION: Short non-coding micro-RNAs (miRNAs) are post-transcriptional factors that directly regulate protein expression by degrading or inhibiting target mRNAs; however, the role of miRNAs in obesity and cardiometabolic disease remains unclarified. Based on our earlier study demonstrating that miR-150 influences lipid metabolism, we have studied effects of miR-150 on systemic metabolism and adipocyte biology. MATERIALS AND METHODS: Metabolic phenotypes including body weight, food intake, body composition, glucose tolerance and insulin sensitivity were assessed in WT and global miR-150 KO male mice fed a high-fat diet...
January 15, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29351482/suppression-of-gut-dysbiosis-reverses-western-diet-induced-vascular-dysfunction
#2
Micah L Battson, Dustin M Lee, Dillon K Jarrell, Shuofei Hou, Kayl E Ecton, Tiffany L Weir, Christopher L Gentile
OBJECTIVE: Vascular dysfunction represents a critical pre-clinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Approach and Results. Male C57BL/6J mice were fed either a standard diet (SD) (n=12) or western diet (WD) (n=24) for 5m, after which time, WD mice were randomized to receive either un-supplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD+Abx) (n=12/group) for 2m...
December 26, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29349446/ameliorative-role-of-camel-whey-protein-and-rosuvastatin-on-induced-dyslipidemia-in-mice
#3
Nashwa Ahmed El-Shinnawy, Sahar Sobhy Abd Elhalem, Nawal Zakaria Haggag, Gamal Badr
The incidence of obesity is rapidly increasing throughout the world. Dyslipidemia is a major risk factor for a number of chronic diseases, including diabetes and cardiovascular diseases. This work presents a novel approach to study the activity of camel whey protein (WP) with antioxidant and anti-inflammatory properties as a cheap dietary protein substance extracted from camel milk to produce satiety and help in building muscles. Mice model suffering from dyslipidemia as a result of feeding on high fat-cholesterol diet for 8 weeks were administrated with either camel WP and/or rosuvastatin for 4 weeks...
January 19, 2018: Food & Function
https://www.readbyqxmd.com/read/29348476/animal-models-of-obesity-and-diabetes-mellitus
#4
REVIEW
Maximilian Kleinert, Christoffer Clemmensen, Susanna M Hofmann, Mary C Moore, Simone Renner, Stephen C Woods, Peter Huypens, Johannes Beckers, Martin Hrabe de Angelis, Annette Schürmann, Mostafa Bakhti, Martin Klingenspor, Mark Heiman, Alan D Cherrington, Michael Ristow, Heiko Lickert, Eckhard Wolf, Peter J Havel, Timo D Müller, Matthias H Tschöp
More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions...
January 19, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29348454/harnessing-insulin-and-leptin-induced-oxidation-of-ptp1b-for-therapeutic-development
#5
Navasona Krishnan, Christopher A Bonham, Ioana A Rus, Om Kumar Shrestha, Carla M Gauss, Aftabul Haque, Ante Tocilj, Leemor Joshua-Tor, Nicholas K Tonks
The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29334590/highly-dispersible-and-bioavailable-curcumin-but-not-native-curcumin-induces-brown-like-adipocyte-formation-in-mice
#6
Sho Nishikawa, Misa Kamiya, Hiroki Aoyama, Mami Nomura, Takuma Hyodo, Aoi Ozeki, Hyunjin Lee, Tsukasa Takahashi, Atsushi Imaizumi, Takanori Tsuda
SCOPE: The induction of brown-like adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity and metabolic disorders via the ability of these cells to release excess energy as heat in association with uncoupling protein 1. Some experimental trials suggest that curcumin (a yellow pigment from turmeric) has a suppressive effect on the accumulation of body fat. However, there is little evidence to show that curcumin induces the formation of brown-like adipocytes and the molecular mechanisms involved remain elusive...
January 15, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29333574/unique-metabolic-activation-of-adipose-tissue-macrophages-in-obesity-promotes-inflammatory-responses
#7
Lily Boutens, Guido J Hooiveld, Sourabh Dhingra, Robert A Cramer, Mihai G Netea, Rinke Stienstra
AIMS/HYPOTHESIS: Recent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development of systemic insulin resistance, yet changes in their intracellular energy metabolism are currently unknown. We therefore set out to study metabolic signatures of adipose tissue macrophages (ATMs) in lean and obese conditions...
January 14, 2018: Diabetologia
https://www.readbyqxmd.com/read/29331414/inhibition-of-fasn-and-er%C3%AE-signalling-during-hyperglycaemia-induced-matrix-specific-emt-promotes-breast-cancer-cell-invasion-via-a-caveolin-1-dependent-mechanism
#8
H A Zielinska, J M P Holly, A Bahl, C M Perks
Since disturbed metabolic conditions such as obesity and diabetes can be critical determinants of breast cancer progression and therapeutic failure, we aimed to determine the mechanism responsible for their pro-oncogenic effects. Using non-invasive, epithelial-like ERα-positive MCF-7 and T47D human breast cancer cells we found that hyperglycaemia induced epithelial to mesenchymal transition (EMT), a key programme responsible for the development of metastatic disease. This was demonstrated by loss of the epithelial marker E-cadherin together with increases in mesenchymal markers such as vimentin, fibronectin and the transcription factor SLUG, together with an enhancement of cell growth and invasion...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29329999/understanding-melanocortin-4-receptor-control-of-neuronal-circuits-toward-novel-therapeutics-for-obesity-syndrome
#9
REVIEW
Sang Hyeon Ju, Gyu-Bon Cho, Jong-Woo Sohn
It is well known that melanocortin-4 receptors (MC4Rs) and central melanocortin pathways regulate food intake, energy expenditure, and glucose homeostasis. Importantly, MC4R deficiency is the most common monogenic cause of human obesity. Interestingly, MC4Rs expressed by distinct central nuclei are responsible for the different physiological function of MC4R stimulation. In addition, MC4Rs activate multiple intracellular and/or synaptic signaling molecules for the regulation of neuronal circuits. Therefore, MC4Rs and the downstream signal molecules are plausible targets for development of novel therapeutics against obesity and obesity-related metabolic disorders...
January 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#10
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29314831/a-fluorescent-probe-to-unravel-functional-features-of-cannabinoid-receptor-cb1-in-human-blood-and-tonsil-immune-system-cells
#11
Mar Martín-Fontecha, Alba Angelina, Beate Rückert, Ainoa Rueda-Zubiaurre, Leticia Martin-Cruz, Willem van de Veen, Mübeccel Akdis, Silvia Ortega-Gutierrez, María L López-Rodrí Guez, Cezmi Akdis, Oscar Palomares
The human endogenous cannabinoid system (ECS) regulates key physiological processes and alterations in its signalling pathways and endocannabinoid levels are associated to diseases such as neurological and neuropsychiatric conditions, cancer, pain and inflammation, obesity, metabolic and different immune related disorders. Immune system cells express the G-protein coupled cannabinoid receptor 1 (CB1) but its functional role has not been fully understood, likely due to the lack of appropriate tools. The availability of novel tools to investigate the role of CB1 in immune regulation might contribute to identify CB1 as a potential novel therapeutic target or biomarker for many diseases...
January 9, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29313726/development-and-characterization-of-a-novel-congenic-rat-strain-for-obesity-and-cancer-research
#12
Ann Marie O'Neill, Erin A Gillaspie, Christine M Burrington, Darin T Lynch, Robert T Dauchy, David E Blask, Paul C Tirrell, Brian A Reis, Melissa J Horsman, Michael W Greene
The association between a Western Diet and colon cancer suggests that dietary factors and/or obesity may contribute to cancer progression. Our objective was to develop a new animal model of obesity and the associated pathophysiology to investigate human cancer independent of dietary components that induce obesity. A novel congenic rat strain was established by introducing the fa allele from the Zucker rat into the Rowett Nude rat to generate a "fatty nude rat". The obese phenotype was first characterized in the new model...
January 9, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29298809/sucrose-non-fermenting-related-kinase-regulates-both-adipose-inflammation-and-energy-homeostasis-in-mice-and-humans
#13
Jie Li, Bin Feng, Yaohui Nie, Ping Jiao, Xiaochen Lin, Mengna Huang, Ran An, Qin He, Huilin Emily Zhou, Arthur Salomon, Kirsten S Sigrist, Zhidan Wu, Simin Liu, Haiyan Xu
Sucrose non-fermenting related kinase (SNRK) is a member of AMPK-related kinase family and its physiological role in adipose energy homeostasis and inflammation remains unknown. We previously reported that SNRK is ubiquitously and abundantly expressed in both white (WAT) and brown adipose tissue (BAT) but adipose SNRK expression level diminishes in obesity. In the current study, we report novel experimental findings from both animal models and human genetics. SNRK is essential for survival since SNRK global deficient pups die within 24 hours after birth...
January 3, 2018: Diabetes
https://www.readbyqxmd.com/read/29291167/epidemic-of-non-alcoholic-fatty-liver-disease-and-hepatocellular-carcinoma
#14
REVIEW
Adnan Said, Aiman Ghufran
Non-alcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors (diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis...
December 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29288362/identification-of-genes-highly-downregulated-in-pancreatic-cancer-through-a-meta-analysis-of-microarray-datasets-implications-for-discovery-of-novel-tumor-suppressor-genes-and-therapeutic-targets
#15
Nalin C W Goonesekere, Wyatt Andersen, Alex Smith, Xiaosheng Wang
PURPOSE: The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease. METHODS: In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets...
December 29, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29286392/overlapping-peptide-library-to-map-qa-1-epitopes-in-a-protein
#16
Yi Xu, Samiksha Wasnik, David J Baylink, Edmundo Carreon Berumen, Xiaolei Tang
Qa-1 (HLA-E in human) belongs to a group of non-classical major histocompatibility complex 1b (MHC-Ib) molecules. Recent data suggest that Qa-1 molecules play important roles in surveying cells for structural and functional integrity, inducing immune regulation, and limiting immune responses to viral infections. Additionally, functional augmentation of Qa-1-restricted CD8+ T cells through epitope immunization has shown therapeutic effects in several autoimmune disease animal models, e.g. experimental allergic encephalomyelitis, collagen-induced arthritis, and non-obese diabetes...
December 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29283909/an-update-on-the-pathogenesis-of-cholesterol-gallstone-disease
#17
Agostino Di Ciaula, David Q-H Wang, Piero Portincasa
PURPOSE OF REVIEW: Gallstone disease is a major epidemiologic and economic burden worldwide, and the most frequent form is cholesterol gallstone disease. RECENT FINDINGS: Major pathogenetic factors for cholesterol gallstones include a genetic background, hepatic hypersecretion of cholesterol, and supersaturated bile which give life to precipitating cholesterol crystals that accumulate and grow in a sluggish gallbladder. Additional factors include mucin and inflammatory changes in the gallbladder, slow intestinal motility, increased intestinal absorption of cholesterol, and altered gut microbiota...
December 27, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/29278671/roles-of-obesity-in-the-development-and-progression-of-breast-cancer
#18
Francesca Reggiani, Francesco Bertolini
Recent preclinical and clinical data accumulate evidence indicating that obesity may worsen the incidence, severity, and mortality of many types of cancer, including breast cancer. In the present review, we discuss the candidate players in this dangerous relationship, namely adipose tissue-related chronic inflammation, immune cell dysregulation, angiogenesis, extracellular matrix stiffness, and genomic instability. Finally, we review some novel therapeutic approaches currently under investigation to prevent and blunt the effects of obesity in breast cancer development and progression, namely caloric restriction, immune checkpoint inhibition, browning of white adipose tissue, and modulation of the microbiota and the immune cell metabolism...
November 2017: Discovery Medicine
https://www.readbyqxmd.com/read/29277329/human-embryonic-stem-cell-derived-cardiomyocytes-as-an-in-vitro-model-to-study-cardiac-insulin-resistance
#19
Ilvy M E Geraets, Dipanjan Chanda, Florence H J van Tienen, Arthur van den Wijngaard, Rick Kamps, Dietbert Neumann, Yilin Liu, Jan F C Glatz, Joost J F P Luiken, Miranda Nabben
Patients with type 2 diabetes (T2D) and/or insulin resistance (IR) have an increased risk for the development of heart failure (HF). Evidence indicates that this increased risk is linked to an altered cardiac substrate preference of the insulin resistant heart, which shifts from a balanced utilization of glucose and long-chain fatty acids (FAs) towards an almost complete reliance on FAs as main fuel source. This shift leads to a loss of endosomal proton pump activity and increased cardiac fat accumulation, which eventually triggers cardiac dysfunction...
December 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29276754/uncovering-a-predictive-molecular-signature-for-the-onset-of-nash-related-fibrosis-in-a-translational-nash-mouse-model
#20
Arianne van Koppen, Lars Verschuren, Anita M van den Hoek, Joanne Verheij, Martine C Morrison, Kelvin Li, Hiroshi Nagabukuro, Adalberto Costessi, Martien P M Caspers, Tim J van den Broek, John Sagartz, Cornelis Kluft, Carine Beysen, Claire Emson, Alain J van Gool, Roel Goldschmeding, Reinout Stoop, Ivana Bobeldijk-Pastorova, Scott M Turner, Guido Hanauer, Roeland Hanemaaijer
Background & Aims: The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. Methods: A time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis...
2018: Cellular and Molecular Gastroenterology and Hepatology
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