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https://www.readbyqxmd.com/read/27909723/inhibition-of-jnk-suppresses-autophagy-and-attenuates-insulin-resistance-in-a-rat-model-of-nonalcoholic-fatty-liver-disease
#1
Hua Yan, Yanqiong Gao, Ying Zhang
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, the pathological process of which is complex. Activation of the c‑Jun N‑terminal kinase (JNK) signaling pathway is associated with the mechanism underlying obesity-induced insulin resistance. Furthermore, the JNK signaling pathway and dysfunctional autophagy serve important roles in hepatic lipid metabolism. However, the exact role of JNK in autophagy and obesity‑induced insulin resistance is not fully understood. Therefore, the present study aimed to investigate the underlying mechanisms by which the JNK signaling pathway regulates autophagy and insulin resistance in fatty liver...
November 24, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27903155/obesity-and-cancer-mechanisms-tumor-microenvironment-and-inflammation
#2
Neil M Iyengar, Ayca Gucalp, Andrew J Dannenberg, Clifford A Hudis
Purpose There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. Methods We review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. Results Locally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27901270/adipose-tissue-inflammation-by-intermittent-hypoxia-mechanistic-link-between-obstructive-sleep-apnoea-and-metabolic-dysfunction
#3
Silke Ryan
Obstructive sleep apnoea (OSA) is a highly prevalent condition and recognized as a major public health burden conveying a significant risk of cardiometabolic diseases and mortality. Type 2 diabetes (T2D), insulin resistance (IR) and glucose tolerance are common in subjects with OSA and this association is at least in part independent of the effects of obesity. Continuous positive airway pressure (CPAP) is the treatment of choice for the majority of patients with OSA but the benefit of CPAP on glycaemic health is uncertain...
November 29, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27899023/ghrelin-function-in-human-obesity-and-type-2-diabetes-a-concise-review
#4
REVIEW
R Churm, J S Davies, J W Stephens, S L Prior
The 28 amino acid hormone, ghrelin, has been found to have various effects on metabolism. This review will focus on the pathways integrated into ghrelin's effect within the hypothalamus, pancreas and adipocytes. The identification of molecules and pathways that regulate ghrelin-mediated lipid retention could establish new mechanisms underlying cellular energy homeostasis. The impact of acyl-ghrelin on glucose metabolism and lipid homeostasis may allow for novel preventative or early intervention therapeutic strategies to treat obesity related type 2 diabetes and associated metabolic dysfunction...
November 29, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27898069/clozapine-modifies-the-differentiation-program-of-human-adipocytes-inducing-browning
#5
E Kristóf, Q-M Doan-Xuan, A K Sárvári, Á Klusóczki, P Fischer-Posovszky, M Wabitsch, Z Bacso, P Bai, Z Balajthy, L Fésüs
Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27895388/acetate-alters-expression-of-genes-involved-in-beige-adipogenesis-in-3t3-l1-cells-and-obese-kk-ay-mice
#6
Satoko Hanatani, Hiroyuki Motoshima, Yuki Takaki, Shuji Kawasaki, Motoyuki Igata, Takeshi Matsumura, Tatsuya Kondo, Takafumi Senokuchi, Norio Ishii, Junji Kawashima, Daisuke Kukidome, Seiya Shimoda, Takeshi Nishikawa, Eiichi Araki
The induction of beige adipogenesis within white adipose tissue, known as "browning", has received attention as a novel potential anti-obesity strategy. The expression of some characteristic genes including PR domain containing 16 is induced during the browning process. Although acetate has been reported to suppress weight gain in both rodents and humans, its potential effects on beige adipogenesis in white adipose tissue have not been fully characterized. We examined the effects of acetate treatment on 3T3-L1 cells and in obese diabetic KK-Ay mice...
November 2016: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/27892934/treatment-with-fgfr2-iiic-monoclonal-antibody-suppresses-weight-gain-and-adiposity-in-kka-y-mice
#7
K Nonogaki, T Kaji, T Yamazaki, Mari Murakami
Expression of β-Kotho, fibroblast growth factor receptor (FGFR)-1c and 2c, which bind FGF21, is decreased in the white adipose tissue of obese mice. The aim of the present study was to determine the role of FGFR2c in the development of obesity and diabetes in KKA(y) mice. Treatment with mouse monoclonal FGFR2-IIIc antibody (0.5 mg kg(-1)) significantly suppressed body weight gain and epididymal white adipose tissue weight in individually housed KKA(y) mice while having no effect on daily food intake. In addition, treatment with FGFR2-IIIc antibody significantly increased plasma-free fatty acid levels while having no effect on blood glucose or plasma FGF21 levels...
November 28, 2016: Nutrition & Diabetes
https://www.readbyqxmd.com/read/27889327/epigenetics-in-non-alcoholic-fatty-liver-disease
#8
REVIEW
Jooho Lee, Yuri Kim, Simonetta Friso, Sang-Woon Choi
Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an emerging health concern. NAFLD is a pathologic condition characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. Excess hepatic fat accumulation results from increased delivery of triglycerides (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a subgroup of NAFLD results in hepatocellular injury and inflammation, which is referred to as non-alcoholic steatohepatitis (NASH), and may progress to irreversible cirrhosis and hepatocellular carcinoma (HCC)...
November 23, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27885461/prevention-and-treatment-effect-of-evogliptin-on-hepatic-steatosis-in-high-fat-fed-animal-models
#9
Mi-Kyung Kim, Yu Na Chae, Gook-Jun Ahn, Chang Yell Shin, Song-Hyen Choi, Eun Kyoung Yang, Yong Sung Sohn, Moon-Ho Son
Dipeptidyl peptidase 4 (DPP4) is an adipokine that interrupts insulin signaling. The resulting insulin resistance exacerbates hepatic steatosis. We previously reported that the novel DPP4 inhibitor evogliptin improves insulin resistance. This study aimed to verify the therapeutic potential of evogliptin for fatty liver. Evogliptin treatment was initiated simultaneously with a high-fat diet (HFD) feeding in normal mice and in a post-24 week HFD-fed rats. In a prevention study, insulin sensitivity was preserved in evogliptin-treated mice after a 16-week treatment...
November 24, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27873088/anti-inflammatory-and-insulin-sensitizing-effects-of-free-fatty-acid-receptors
#10
Junki Miyamoto, Mayu Kasubuchi, Akira Nakajima, Ikuo Kimura
Chronic low-grade inflammation in macrophages and adipose tissues can promote the development of obesity and type 2 diabetes. Free fatty acids (FFAs) have important roles in various tissues, acting as both essential energy sources and signaling molecules. FFA receptors (FFARs) can modulate inflammation in various types of cells and tissues; however the underlying mechanisms mediating these effects are unclear. FFARs are activated by specific FFAs; for example, GPR40 and GPR120 are activated by medium and long chain FFAs, GPR41 and GPR43 are activated by short chain FFAs, and GPR84 is activated by medium-chain FFAs...
November 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27869139/the-transcription-cofactor-crtc1-protects-from-aberrant-hepatic-lipid-accumulation
#11
Hwijin Kim
Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging global health-problem. NAFLD encompasses a range of conditions associated with hepatic steatosis, aberrant accumulation of fat in hepatocytes. Although obesity and metabolic syndrome are considered to have a strong association with NAFLD, genetic factors that predispose liver to NAFLD and molecular mechanisms by which excess hepatic lipid develops remain largely unknown. We report that the transcription cofactor CRTC1 confers broad spectrum protection against hepatic steatosis development...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856635/micrornaa-155-deficiency-leads-to-decreased-atherosclerosis-increased-white-adipose-tissue-obesity-and-nonalcoholic-fatty-liver-disease-a-novel-mouse-model-of-obesity-paradox
#12
Anthony Virtue, Candice Johnson, Jahaira Lopez-Pastraña, Ying Shao, Hangfei Fu, Xinyuan Li, Ya-Feng Li, Ying Yin, Jietang Mai, Victor Rizzo, Michael Tordoff, Zsolt Bagi, Huimin Shan, Xiaohua Jiang, Hong Wang, Xiao-Feng Yang
Obesity paradox (OP) describes a widely observed clinical finding of improved cardiovascular fitness and survival in some overweight or obese patients. The molecular mechanisms underlying OP remain enigmatic partly due to a lack of animal models mirroring OP in patients. Using apolipoprotein E knockout (ApoE-/-) mice on high-fat (HF) diet as an atherosclerotic obesity model, we demonstrated: 1) microRNA-155 (miRNA-155, miR-155) is significantly upregulated in aortas of ApoE-/- mice; and miR-155 deficiency in ApoE-/- mice inhibits atherosclerosis; 2) ApoE-/-/miR-155-/- (DKO) mice show HF diet-induced obesity, adipocyte hypertrophy and present with nonalcoholic fatty liver disease (NAFLD); 3) DKO mice demonstrate HF diet-induced elevations of plasma leptin, resistin, fed-state and fasting insulin, increased expression of adipogenic transcription factors, but lack glucose intolerance and insulin resistance...
November 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27849358/immune-modulation-of-brown-ing-adipose-tissue-in-obesity
#13
Susan M van den Berg, Andrea D van Dam, Patrick C N Rensen, Menno P J de Winther, Esther Lutgens
Obesity is associated with a variety of medical conditions such as type 2 diabetes and cardiovascular diseases and is therefore responsible for high morbidity and mortality rates. Increasing energy expenditure by brown adipose tissue (BAT) is a current novel strategy to reduce the excessive energy stores in obesity. Brown adipocytes burn energy to generate heat and are mainly activated upon cold exposure. As prolonged cold exposure is not a realistic therapy, researchers worldwide are searching for novel ways to activate BAT and/or induce beiging of WAT...
November 16, 2016: Endocrine Reviews
https://www.readbyqxmd.com/read/27848888/immunotherapy-in-liver-diseases-a-balance-between-immunity-and-tolerance
#14
Alaknanda Mishra, Pramod K Upadhyay, Perumal Nagarajan
In today's context when liver diseases have spread across countries and people of all ages, it is of high importance to consider novel methods of non-toxic and long lived therapeutics. Among various therapies, immunotherapy for acute and chronic liver diseases is rapidly moving to the forefront among treatment options in hepatology medicine. Liver has a unique immuno- biological advantage which is utilized to maintain a balance between immunity and tolerance. This intricate balance of hepatic immune cells can be modulated to effect treatments in various liver diseases...
November 16, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27826372/vascular-inflammation-a-novel-access-route-for-nanomedicine
#15
Roberto Molinaro, Christian Boada, Guillermo Medrano Del Rosal, Kelly A Hartman, Claudia Corbo, Elizabeth D Andrews, Naama E Toledano-Furman, John P Cooke, Ennio Tasciotti
Despite an improved understanding of its pathophysiology and a wide range of new treatments, cardiovascular disease (CVD) remains a serious public health issue and the number one cause of mortality in the United States. Conditions that promote chronic systemic inflammation, such as obesity, cancer, and autoimmune and infectious diseases, are now known to play an important role in promoting CVD by inducing the expression of endothelial adhesion molecules and chemokines; these in turn promote leukocyte adherence and infiltration, which initiates and spurs the progression of CVD...
September 2016: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/27825851/targeting-the-apelin-pathway-as-a-novel-therapeutic-approach-for-cardiovascular-diseases
#16
Jiu-Chang Zhong, Zhen-Zhou Zhang, Wang Wang, Shaun M K McKinnie, John C Vederas, Gavin Y Oudit
The apelin/apelin receptor system is widely distributed and has a dominant role in cardiovascular homeostasis and disease. The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is subsequently cleaved to generate a family of apelin peptides that possess similar functions but display different tissue distribution, potency and receptor binding affinity. Loss-of-function experiments using the apelin and the apelin receptor knockout mice and gain-of-function experiments using apelin peptides have delineated a well-defined role of the apelin axis in cardiovascular physiology and diseases...
November 4, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27815373/inhibiting-insulin-mediated-%C3%AE-2ar-activation-prevents-diabetes-associated-cardiac-dysfunction
#17
Qingtong Wang, Yongming Liu, Qin Fu, Bing Xu, Yuan Zhang, Sungjin Kim, Ruensern Tan, Federica Barbagallo, Toni M West, Ethan J Anderson, Wei Wei, E Dale Abel, Yang K Xiang
BACKGROUND: -Type-2 diabetes and obesity independently increases the risk of heart failure via incompletely understood mechanisms. We propose that hyperinsulinemia might promote adverse consequences in hearts of subjects with type-2 diabetes and obesity. METHODS: -High fat diet feeding was used to induce obesity and diabetes in wild type mice or mice lacking β 2-adrenergic receptor (β2AR) or β -arrestin2. Wild type mice fed with high fat diet were treated with β -blocker carvedilol or G-protein receptor kinase 2 (GRK2) inhibitor...
November 4, 2016: Circulation
https://www.readbyqxmd.com/read/27814604/sphingolipids-in-obesity-and-related-complications
#18
Krishna M Boini, Min Xia, Saisudha Koka, Todd W B Gehr, Pin-Lan Li
  Sphingolipids are biologically active lipids ubiquitously produced in all vertebrate cells. Asides from structural components of cell membrane, sphingolipids also function as intracellular and extracellular mediators that regulate many important physiological cellular processes including cell survival, proliferation, apoptosis, differentiation, migration and immune processes. Recent studies have also indicated that disruption of sphingolipid metabolism is strongly associated with different diseases that exhibit diverse neurological and metabolic consequences...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27810172/extracellular-vesicles-novel-mediators-of-cell-communication-in-metabolic-disease
#19
REVIEW
Isabel Huang-Doran, Chen-Yu Zhang, Antonio Vidal-Puig
Metabolic homeostasis emerges from the complex, multidirectional crosstalk between key metabolic tissues including adipose tissue, liver, and skeletal muscle. This crosstalk, traditionally mediated by hormones and metabolites, becomes dysregulated in human diseases such as obesity and diabetes. Extracellular vesicles (EVs; including exosomes) are circulating, cell-derived nanoparticles containing proteins and nucleic acids that interact with and modify local and distant cellular targets. Accumulating evidence, reviewed herein, supports a role for extracellular vesicles in obesity-associated metabolic disturbance, particularly the local and systemic inflammation characteristic of adipose and hepatic stress...
October 31, 2016: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27803933/endothelial-microparticles-act-as-novel-diagnostic-and-therapeutic-biomarkers-of-diabetes-and-its-complications-a-literature-review
#20
REVIEW
Fan Deng, Shuang Wang, Liangqing Zhang
Diabetes mellitus- (DM-) related vascular diseases attract increased attention due to their high morbidity and mortality. The incidence of obesity, atherosclerosis, coronary heart disease, hypertension, and dyslipidemia is significantly higher in DM patients, with an earlier onset and faster progression compared with non-DM patients. DM-related vascular diseases including macrovascular and microvascular complications are characterized by endothelial dysfunction. Therefore, a better understanding of the etiology and mechanisms of endothelial dysfunction is important for the diagnosis and treatment of DM...
2016: BioMed Research International
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