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https://www.readbyqxmd.com/read/28439947/sirt1-hsf1-hsps-pathway-is-essential-for-exenatide-alleviated-lipid-induced-hepatic-endoplasmic-reticulum-stress
#1
Xiaobin Zheng, Fen Xu, Hua Liang, Huanyi Cao, Mengyin Cai, Wen Xu, Jianping Weng
Recent studies have indicated lipid-induced endoplasmic reticulum (ER) stress to be a major contributor to the progression of hepatic steatosis. Exenatide (Exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve hepatic steatosis with accumulating evidence. In this study, we investigated whether exenatide could alleviate lipid-induced hepatic ER stress through mammal sirtuin1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice challenged with a high-fat diet (HFD) were then treated with exenatide or normal saline by intraperitoneal injection for 4 weeks...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28435972/-glp-1-gip-gcg-receptor-triagonist-improves-the-cognitive-behaviors-in-triple-transgenic-mice-of-alzheimer-s-disease
#2
Juan-Juan Jiao, Christian Hölscher, Tian Li, Xue-Fan Dong, Xue-Song Qu, Yue Cao, Mei-Na Wu, Zhao-Jun Wang, Jin-Shun Qi
Alzheimer's disease (AD) is a progressively neurodegenerative disorder, which seriously affects human health but is still irreversible up to now. Recent studies indicate that type 2 diabetes mellitus (T2DM) is an important risk factor for AD, and the drugs used for treatment of T2DM have shown some neuroprotective effects in the treatment of AD. Glucagon-like peptide-1 (GLP-1)/ glucose-dependent insulinotropic polypeptide (GIP)/glucagon (Gcg) receptor Triagonist is a new monomeric polypeptide equally activating the GLP-1/GIP/Gcg receptors, which is built on the basis of GLP-1/Gcg receptor coagonist core sequence, and incorporated with partial amino acids of GIP...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28430907/food-intake-affects-sperm-egg-fusion-through-the-gip-psg17-axis-in-mice
#3
Tatsunori Shimizu, Takehiro Sato, Katsushi Tsukiyama, Hiroki Fujita, Shunsuke Kato, Manabu Hoizumi, Hiromitsu Shirasawa, Takuma Narita, Yukihiro Terada, Yutaka Seino, Yuichiro Yamada
In addition to overeating, starvation also reduces fecundity in mammals. However, little is known about the molecular mechanisms linking food intake to fertility, especially in males. Gastric inhibitory polypeptide (GIP), which is released from intestinal K-cells after meal ingestion, stimulates insulin secretion from pancreatic β-cells through the action of incretin and has several extra-pancreatic effects. Here, we identified GIP receptor (Gipr) expression in mouse spermatids. Microarray analysis revealed that pregnancy-specific glycoprotein 17 (Psg17), a potential CD9-binding partner, was significantly decreased in GIP receptor-knockout (Gipr-/-) testes...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430139/the-metalloproteinase-adam28-promotes-metabolic-dysfunction-in-mice
#4
Lakshini Herat, Caroline Rudnicka, Yasunori Okada, Satsuki Mochizuki, Markus Schlaich, Vance Matthews
Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28429777/interleukin-6-increases-the-expression-and-activity-of-insulin-degrading-enzyme
#5
Mirian A Kurauti, José M Costa-Júnior, Sandra M Ferreira, Gustavo J Santos, Carlos H G Sponton, Everardo M Carneiro, Guilherme D Telles, Mara P T Chacon-Mikahil, Cláudia R Cavaglieri, Luiz F Rezende, Antonio C Boschero
Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421037/lipid-processing-in-the-brain-a-key-regulator-of-systemic-metabolism
#6
REVIEW
Kimberley D Bruce, Andrea Zsombok, Robert H Eckel
Metabolic disorders, particularly aberrations in lipid homeostasis, such as obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest together as the metabolic syndrome (MetS). Despite major advances in our understanding of the pathogenesis of these disorders, the prevalence of the MetS continues to rise. It is becoming increasingly apparent that intermediary metabolism within the central nervous system is a major contributor to the regulation of systemic metabolism. In particular, lipid metabolism within the brain is tightly regulated to maintain neuronal structure and function and may signal nutrient status to modulate metabolism in key peripheral tissues such as the liver...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28414326/mesenchymal-stem-cells-in-obesity-insights-for-translational-applications
#7
Kenichi Matsushita, Victor J Dzau
Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been withdrawn from market due to adverse side effects. Bariatric surgery therefore remains the most effective therapy for severe cases, although such surgery is invasive and researchers continue to seek new control strategies for obesity...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28411689/moutan-cortex-and-paeoniae-radix-rubra-reverse-high-fat-diet-induced-metabolic-disorder-and-restore-gut-microbiota-homeostasis
#8
Ling-Jun Zhong, Zhi-Sheng Xie, Hua Yang, Ping Li, Xiao-Jun Xu
The present study was designed to investigate the therapeutic effcts of Moutan Cortex (CM, root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra (PR, root of Paeonia veitchii Lynch) on metabolic disorders, focusing on the infuence of CM and PR on the obesity-related gut microbiota homeostasis. The diet-induced obese (DIO) mouse model was used to test the therapeutic effects of CM and PR. The mice were orally administered with CM and PR for 6 weeks, and oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed to evaluate the insulin sensitivity of the mice...
March 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28396567/inhibition-of-pikfyve-prevents-myocardial-apoptosis-and-hypertrophy-through-activation-of-sirt3-in-obese-mice
#9
Helene Tronchere, Mathieu Cinato, Andrei Timotin, Laurie Guitou, Camille Villedieu, Helene Thibault, Delphine Baetz, Bernard Payrastre, Philippe Valet, Angelo Parini, Oksana Kunduzova, Frederic Boal
PIKfyve is an evolutionarily conserved lipid kinase that regulates pleiotropic cellular functions. Here, we identify PIKfyve as a key regulator of cardiometabolic status and mitochondrial integrity in chronic diet-induced obesity. In vitro, we show that PIKfyve is critical for the control of mitochondrial fragmentation and hypertrophic and apoptotic responses to stress. We also provide evidence that inactivation of PIKfyve by the selective inhibitor STA suppresses excessive mitochondrial ROS production and apoptosis through a SIRT3-dependent pathway in cardiomyoblasts...
April 10, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28389409/anti-obesity-effect-of-a-novel-caffeine-loaded-dissolving-microneedle-patch-in-high-fat-diet-induced-obese-c57bl-6j-mice
#10
Manita Dangol, Suyong Kim, Cheng Guo Li, Shayan Fakhraei Lahiji, Mingyu Jang, Yonghao Ma, Inyoung Huh, Hyungil Jung
Natural products such as caffeine have been found to be effective in reducing body weight through lipolysis. Here, we report the successful loading of caffeine onto dissolving microneedle following inhibition of its crystal growth by hyaluronic acid (HA), the matrix material of the dissolving microneedle (DMN). Further, the anti-obesity activity of caffeine was evaluated in high-fat diet-induced obese C57BL/6J mice. After 6weeks of caffeine loaded dissolving microneedle patch (CMP) administration, lipolysis improved significantly as shown by leptin and adiponectin activity, which resulted in considerable weight loss of about 12...
April 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28387458/anti-tumorigenic-potential-of-a-novel-orlistat-aicar-combination-in-prostate-cancer-cells
#11
Clayton Wright, Anand Krishnan V Iyer, Vivek Kaushik, Neelam Azad
Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men worldwide. Fatty acid synthase (FASN) is reported to be overexpressed in several cancers including PCa, and this has led to clinical cancer treatments that utilize various FASN inhibitors such as the anti-obesity drug, Orlistat. However, pharmacological limitations have impeded the progress in cancer treatments expected thus far with FASN inhibition. In this study, we investigated a novel therapeutic combination to enhance the toxic potential of Orlistat in three different PCa cell-lines (DU145, PC3, and LNCaP)...
April 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28381504/insulin-receptor-substrate-signaling-controls-cardiac-energy-metabolism-and-heart-failure
#12
Cathy A Guo, Shaodong Guo
The heart is an insulin-dependent and energy consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth, and survival. Heart failure is highly associated with insulin resistance and heart failure patients suffer from the cardiac energy deficiency, structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics, and impairing cardiac contractility...
April 5, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28377875/astrocyte-ikk%C3%AE-nf-%C3%AE%C2%BAb-signaling-is-required-for-diet-induced-obesity-and-hypothalamic-inflammation
#13
J D Douglass, M D Dorfman, R Fasnacht, L D Shaffer, J P Thaler
OBJECTIVE: Obesity and high fat diet (HFD) consumption in rodents is associated with hypothalamic inflammation and reactive gliosis. While neuronal inflammation promotes HFD-induced metabolic dysfunction, the role of astrocyte activation in susceptibility to hypothalamic inflammation and diet-induced obesity (DIO) remains uncertain. METHODS: Metabolic phenotyping, immunohistochemical analyses, and biochemical analyses were performed on HFD-fed mice with a tamoxifen-inducible astrocyte-specific knockout of IKKβ (Gfap(CreER)Ikbkb(fl/fl), IKKβ-AKO), an essential cofactor of NF-κB-mediated inflammation...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377725/gut-microbiota-dependent-metabolite-trimethylamine-n-oxide-contributes-to-cardiac-dysfunction-in-western-diet-induced-obese-mice
#14
Kui Chen, Xiaoqian Zheng, Mingchen Feng, Dongliang Li, Hongqi Zhang
Excessive consumption of diets high in sugars and saturated fat, frequently known as western diet (WD), may lead to obesity and metabolic syndrome. Recent evidence shows that WD-induced obesity impairs cardiac function, but the underlying mechanisms are not fully understood. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. We tested the hypothesis that elevated circulating TMAO levels contribute to cardiac dysfunction in WD-induced obesity...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28372330/the-gut-microbiota-and-alzheimer-s-disease
#15
Chunmei Jiang, Guangning Li, Pengru Huang, Zhou Liu, Bin Zhao
The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways...
March 29, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28363724/hidden-targets-of-ubiquitin-proteasome-system-to-prevent-diabetic-nephropathy
#16
REVIEW
Santosh Kumar Goru, Almesh Kadakol, Anil Bhanudas Gaikwad
Diabetic nephropathy (DN) is the major cause of end stage renal failure. Although, several therapeutic targets have emerged to prevent the progression of DN, the number of people with DN still continues to rise worldwide, suggesting an urgent need of novel targets to prevent DN completely. Currently, the role of ubiquitin proteasome system (UPS) has been highlighted in the pathogenesis and progression of various diseases like obesity, insulin resistance, atherosclerosis, cancers, neurodegerative disorders and including secondary complications of diabetes...
March 29, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28360349/gut-microbiota-in-cardiovascular-health-and-disease
#17
REVIEW
W H Wilson Tang, Takeshi Kitai, Stanley L Hazen
Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases...
March 31, 2017: Circulation Research
https://www.readbyqxmd.com/read/28359874/in-silico-analysis-of-nonsynonymous-single-nucleotide-polymorphisms-of-the-human-adiponectin-receptor-2-adipor2-gene
#18
Md Solayman, Md Abu Saleh, Sudip Paul, Md Ibrahim Khalil, Siew Hua Gan
Polymorphisms of the ADIPOR2 gene are frequently linked to a higher risk of developing diseases including obesity, type 2 diabetes and cardiovascular diseases. Though mutations of the ADIPOR2 gene are detrimental, there is a lack of comprehensive in silico analyses of the functional and structural impacts at the protein level. Considering the involvement of ADIPOR2 in glucose uptake and fatty acid oxidation, an in silico functional analysis was conducted to explore the possible association between genetic mutations and phenotypic variations...
March 14, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28356045/pathophysiological-implications-of-dipeptidyl-peptidases
#19
Akira Sato, Hisakazu Ogita
Dipeptidyl peptidases (DPPs) belong to one of the protease families classified under EC 3.4.14 in the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. DPPs family consists of eight members in the mammalian species. They play a role in oligopeptide N-terminal processing and degradation of bioactive peptides. Over the past 20 years, most of the studies have been focused on DPP 4 that has important roles in metabolism and immunity. A large number of pharmacological inhibitors against DPP 4 have been tested rigorously and some of them are now used in the treatment of type 2 diabetes and obesity...
March 29, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28346848/cardiovascular-protective-effects-and-clinical-applications-of-resveratrol
#20
Sanghyun Cho, Kyung Namkoong, Minji Shin, Jueun Park, Eunyeong Yang, Jinsoo Ihm, Vu Thi Thu, Hyoung Kyu Kim, Jin Han
Resveratrol is a naturally occurring phenol that is generated by plant species following injury or attack by bacterial and fungal pathogens. This compound was first described as the French Paradox in 1992. Later in 2003, resveratrol was reported to activate sirtuins in yeast cells. Recent experimental studies have found that resveratrol offers a variety of benefits that include both anticarcinogenic and anti-inflammatory effects in addition to the ability to reverse obesity, attenuate hyperglycemia and hyperinsulinemia, protect heart and endothelial function, and increase the life span...
April 2017: Journal of Medicinal Food
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