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Novel obesity therapeutic

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https://www.readbyqxmd.com/read/28544245/ghrelin-receptor-inverse-agonists-as-a-novel-therapeutic-approach-against-obesity-related-metabolic-disease
#1
Kathrin Abegg, Lara Bernasconi, Melanie Hutter, Lynda Whiting, Claudio Pietra, Claudio Giuliano, Thomas A Lutz, Thomas Riediger
AIMS: Ghrelin is implicated in the control of energy balance and glucose homeostasis. The ghrelin receptor exhibits ligand independent constitutive activity, which can be pharmacologically exploited to induce inverse ghrelin actions. Since ghrelin receptor inverse agonists (GHSR-IA) might be effective for the treatment of obesity-related metabolic disease, we tested two novel synthetic compounds GHSR-IA1 and GHSR-IA2. MATERIALS AND METHODS: In functional cell assays, electrophysiogical and immunohistochemical experiments, we demonstrated inverse agonist activity for GHSR-IA1 and GHSR-IA2...
May 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28542577/leptin-signals-via-tgfb1-to-promote-metastatic-potential-and-stemness-in-breast-cancer
#2
Ameet K Mishra, Christopher R Parish, Ma-Li Wong, Julio Licinio, Anneke C Blackburn
Epidemiological studies have shown obesity to be linked with poorer outcomes in breast cancer patients. The molecular mechanisms responsible for the increased risk of invasive/metastatic disease with obesity are complex, but may include elevated levels of adipokines such as leptin. Using physiological levels of leptin found in obesity in a novel chronic in vitro treatment model (≤200 ng/ml for 14 days), we confirmed the occurrence of leptin-mediated changes in growth, apoptosis and metastatic behavior, and gene expression changes representing epithelial-to-mesenchymal transition (EMT) and a cancer stem cell (CSC) like phenotype in breast epithelial and cancer cell lines (MCF10A, MCF10AT1, MCF7 and MDA-MB-231)...
2017: PloS One
https://www.readbyqxmd.com/read/28536316/-adipose-stem-cell-system
#3
Yumiko Oishi, Ichiro Manabe
Adipose tissues are the major organ that controls systemic energy metabolism and maintain homeostasis by storing lipids, dissipating them as heat, and producing various adipokines. There are two major classes of adipocytes: white and brown adipocytes. White adipocytes store and release lipids, while brown adipocytes burn substrates to produce heat. In addition to classical brown adipose tissues consisting of brown adipocytes, cold exposure and β3 stimulation induce development of brown cell-like "beige" adipocytes in white adipose tissues...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28534956/effects-of-octreotide-on-hepatic-glycogenesis-in-rats-with-high-fat-diet%C3%A2-induced-obesity
#4
Xiao-Xia Wang, Ting Ye, Mao Li, Xian Li, Ou Qiang, Cheng-Wei Tang, Rui Liu
Reduced hepatic glycogenesis is one of the most important causes of metabolic abnormalities in non‑alcoholic fatty liver disease. Octreotide, a somatostatin analogue, has been demonstrated to promote weight loss and improve metabolic disorders in mice with high fat diet (HFD)‑induced obesity. However, whether octreotide affects hepatic glycogenesis is unknown. The aim of the present study was to verify the effects of octreotide on hepatic glycogenesis in rats with HFD‑induced obesity. Male Sprague‑Dawley rats were fed a standard diet or a HFD for 24 weeks...
May 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28529328/perivascular-adipose-tissue-epiphenomenon-or-local-risk-factor
#5
REVIEW
K Schäfer, I Drosos, S Konstantinides
Obesity is associated with an increased cardiovascular risk, but the mechanisms underlying the link between increased body weight and vascular disease are incompletely understood. Over the past 15 years, perivascular adipose tissue has emerged as active component of the vessel wall involved in vascular homeostasis. However, perivascular adipose tissue can adopt detrimental properties under the influence of obesity and other factors and contribute actively to the pathophysiology of cardiovascular disease. Conversely, changes of the vessel wall may negatively affect perivascular adipose tissue qualities...
May 22, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#6
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28521862/bile-acid-binding-resin-prevents-fat-accumulation-through-intestinal-microbiota-in-high-fat-diet-induced-obesity-in-mice
#7
Yukie Kusumoto, Junichiro Irie, Kaho Iwabu, Hirotsune Tagawa, Arata Itoh, Mari Kato, Nana Kobayashi, Kumiko Tanaka, Rieko Kikuchi, Masataka Fujita, Yuya Nakajima, Kohkichi Morimoto, Taichi Sugizaki, Satoru Yamada, Toshihide Kawai, Mitsuhiro Watanabe, Yuichi Oike, Hiroshi Itoh
BACKGROUND: Bile acid binding resin (BAR) absorbs intestinal bile acids, and improves obesity and metabolic disorders, but the precise mechanism remains to be clarified. Recent findings reveal that obesity is associated with skewed intestinal microbiota. Thus, we investigated the effect of BAR on intestinal microbiota and the role of microbiota in the prevention of obesity in high-fat diet-induced obesity in mice. PROCEDURES: Male Balb/c mice were fed a low-fat diet (LFD), high-fat diet (HFD), or HFD with BAR (HFD+BAR), and then metabolic parameters, caecal microbiota, and metabolites were investigated...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28512432/whole-body-cryotherapy-in-athletes-from-therapy-to-stimulation-an-updated-review-of-the-literature
#8
REVIEW
Giovanni Lombardi, Ewa Ziemann, Giuseppe Banfi
Nowadays, whole-body cryotherapy is a medical physical treatment widely used in sports medicine. Recovery from injuries (e.g., trauma, overuse) and after-season recovery are the main purposes for application. However, the most recent studies confirmed the anti-inflammatory, anti-analgesic, and anti-oxidant effects of this therapy by highlighting the underlying physiological responses. In addition to its therapeutic effects, whole-body cryotherapy has been demonstrated to be a preventive strategy against the deleterious effects of exercise-induced inflammation and soreness...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28508477/the-novel-intracellular-protein-creg-inhibits-hepatic-steatosis-obesity-and-insulin-resistance
#9
Quan-Yu Zhang, Ling-Ping Zhao, Xiao-Xiang Tian, Cheng-Hui Yan, Yang Li, Yan-Xia Liu, Pi-Xiao Wang, Xiao-Jing Zhang, Ya-Ling Han
Cellular repressor of E1A-stimulated genes (CREG), a novel cellular glycoprotein, has been identified as a suppressor of various cardiovascular diseases (CVDs) because of its capacity to reduce hyperplasia, maintain vascular homeostasis, and promote endothelial restoration. However, the effects and mechanism of CREG in metabolic disorder and hepatic steatosis remain unknown. Here, we report that hepatocyte-specific CREG deletion dramatically exacerbates high fat diet (HFD) and leptin deficiency-induced (ob/ob) adverse effects such as obesity, hepatic steatosis and metabolic disorders, whereas a beneficial effect is conferred by CREG overexpression...
May 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28507012/dietary-factors-promoting-brown-and-beige-fat-development-and-thermogenesis
#10
REVIEW
Meshail Okla, Jiyoung Kim, Karsten Koehler, Soonkyu Chung
Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity to dissociate cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Adult humans possess a substantial amount of BAT in the form of constitutively active brown fat or inducible beige fat. BAT activity in humans is inversely correlated with adiposity, blood glucose concentrations, and insulin sensitivity; this suggests that strategies aimed at BAT-mediated bioenergetics are an attractive therapeutic target in combating the continuing epidemic of obesity and diabetes...
May 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28496128/a-systems-genetics-approach-identified-gpd1l-and-its-molecular-mechanism-for-obesity-in-human-adipose-tissue
#11
Hao He, Dianjianyi Sun, Yong Zeng, Ruifeng Wang, Wei Zhu, Shaolong Cao, George A Bray, Wei Chen, Hui Shen, Frank M Sacks, Lu Qi, Hong-Wen Deng
To explore novel molecular mechanisms underlying obesity, we applied a systems genetics framework to integrate risk genetic loci from the largest body mass index (BMI) genome-wide association studies (GWAS) meta-analysis with mRNA and microRNA profiling in adipose tissue from 200 subjects. One module was identified to be most significantly associated with obesity and other metabolic traits. We identified eight hub genes which likely play important roles in obesity metabolism and identified microRNAs that significantly negatively correlated with hub genes...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28495997/extracellular-vesicles-in-metabolic-syndrome
#12
REVIEW
M Carmen Martínez, Ramaroson Andriantsitohaina
Metabolic syndrome defines a cluster of interrelated risk factors for cardiovascular disease and diabetes mellitus. These factors include metabolic abnormalities, such as hyperglycemia, elevated triglyceride levels, low high-density lipoprotein cholesterol levels, high blood pressure, and obesity, mainly central adiposity. In this context, extracellular vesicles (EVs) may represent novel effectors that might help to elucidate disease-specific pathways in metabolic disease. Indeed, EVs (a terminology that encompasses microparticles, exosomes, and apoptotic bodies) are emerging as a novel mean of cell-to-cell communication in physiology and pathology because they represent a new way to convey fundamental information between cells...
May 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28476630/membrane-lipid-therapy-a-historical-perspective-of-membrane-targeted-therapies-from-lipid-bilayer-structure-to-the-pathophysiological-regulation-of-cells
#13
REVIEW
Pablo V Escribá
Our current understanding of membrane lipid composition, structure and functions has led to the investigation of their role in cell signaling, both in healthy and pathological cells. As a consequence, therapies based on the regulation of membrane lipid composition and structure have been recently developed. This novel field, known as Membrane Lipid Therapy, is growing and evolving rapidly, providing treatments that are now in use or that are being studied for their application to oncological disorders, Alzheimer's disease, spinal cord injury, stroke, diabetes, obesity, and neuropathic pain...
May 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28474284/damage-associated-molecular-patterns-in-the-pathogenesis-of-osteoarthritis-potentially-novel-therapeutic-targets
#14
REVIEW
John H Rosenberg, Vikrant Rai, Matthew F Dilisio, Devendra K Agrawal
Osteoarthritis (OA) is a chronic disease that degrades the joints and is often associated with increasing age and obesity. The two most common sites of OA in adults are the knee and hip joints. Increased mechanical stress on the joint from obesity can cause the articular cartilage to degrade and release damage-associated molecular patterns (DAMPs). These DAMPs are involved in various molecular pathways that interact with nuclear factor-kappa B and result in the transcription of inflammatory cytokines and activation of matrix metalloproteinases that progressively destroy cartilage...
May 4, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28469250/development-of-a-novel-zebrafish-model-for-type-2-diabetes-mellitus
#15
Liqing Zang, Yasuhito Shimada, Norihiro Nishimura
Obesity is a major cause of type 2 diabetes mellitus (T2DM) in mammals. We have previously established a zebrafish model of diet-induced obesity (DIO zebrafish) by overfeeding Artemia. Here we created DIO zebrafish using a different method to induce T2DM. Zebrafish were overfed a commercially available fish food using an automated feeding system. We monitored the fasting blood glucose levels in the normal-fed group (one feed/day) and overfed group (six feeds/day) over an 8-week period. The fasting blood glucose level was significantly increased in DIO zebrafish compared with that of normal-fed zebrafish...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28466023/adipose-tissue-specialized-immunologic-features-might-be-the-potential-therapeutic-target-of-prospective-medicines-for-obesity
#16
REVIEW
Fan Yao, Ming Zhang, Li Chen
Excessive lipid accumulation in adipose tissue is either the source of obesity or the cause and result of chronic local inflammation, and recent studies indicate that the accumulation may induce many other specialized immunologic features with macrophages and epidemic diseases. We analyze the effective stages of immune cells in adipose tissue, including macrophage recruitment, macrophage polarization, and macrophage-like phenotype preadipocyte possession to find optimal sites as drug targets. Subsequently, some main signaling pathways are summarized in this review, including the AMP-activated protein kinase (AMPK) pathway, the JNK signaling pathway, and a novel one, the Notch signaling pathway...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28465407/role-of-nrf2-signaling-in-the-regulation-of-vascular-bk-channel-beta-1-subunit-expression-and-bk-channel-function-in-high-fat-diet-induced-diabetic-mice
#17
Tong Lu, Xiaojing Sun, Yong Li, Qiang Chai, Xiao-Li Wang, Hon-Chi Lee
The large conductance Ca(2+)-activated K(+) (BK) channel β1 subunit (BK-β1) is a key modulator of BK channel electrophysiology and the downregulation of BK-β1 protein expression in vascular smooth muscle cells (SMCs) underlies diabetic vascular dysfunction. In this study, we hypothesized that the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway plays a significant role in the regulation of coronary BK channel function and vasodilation in high fat diet (HFD)-induced obese/diabetic mice...
May 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28462811/sphingolipids-and-lipoproteins-in-health-and-metabolic-disorders
#18
REVIEW
Jahangir Iqbal, Meghan T Walsh, Samar M Hammad, M Mahmood Hussain
Sphingolipids are structurally and functionally diverse molecules with significant physiologic functions and are found associated with cellular membranes and plasma lipoproteins. The cellular and plasma concentrations of sphingolipids are altered in several metabolic disorders and may serve as prognostic and diagnostic markers. Here we discuss various sphingolipid transport mechanisms and highlight how changes in cellular and plasma sphingolipid levels contribute to cardiovascular disease, obesity, diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD)...
April 24, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28454890/plasticity-of-vagal-afferent-signaling-in-the-gut
#19
REVIEW
Gintautas Grabauskas, Chung Owyang
Vagal sensory neurons mediate the vago-vagal reflex which, in turn, regulates a wide array of gastrointestinal functions including esophageal motility, gastric accommodation and pancreatic enzyme secretion. These neurons also transmit sensory information from the gut to the central nervous system, which then mediates the sensations of nausea, fullness and satiety. Recent research indicates that vagal afferent neurons process non-uniform properties and a significant degree of plasticity. These properties are important to ensure that vagally regulated gastrointestinal functions respond rapidly and appropriately to various intrinsic and extrinsic factors...
April 10, 2017: Medicina
https://www.readbyqxmd.com/read/28452943/pectic-bee-pollen-polysaccharide-from-rosa-rugosa-alleviates-diet-induced-hepatic-steatosis-and-insulin-resistance-via-induction-of-ampk-mtor-mediated-autophagy
#20
Xinzhi Li, Haiquan Gong, Siwen Yang, Lulu Yang, Yuying Fan, Yifa Zhou
Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by (13)C-NMR and Fourier transform-infrared spectroscopy (FT-IR). Using high glucose and fatty acids-treated HepG2 cells and high fat diet (HFD)-induced obesity mice, we detected its effect on insulin function and lipid metabolism based on autophagy. RBPP-P contained arabinogalactan, rhamnogalacturonan I, and homogalacturonan domains...
April 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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