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https://www.readbyqxmd.com/read/28647369/synthesis-of-cytochrome-c-oxidase-1-sco1-inhibits-insulin-sensitivity-by-decreasing-copper-levels-in-adipocytes
#1
Xiang-Bo Wei, Liang Guo, Yang Liu, Shui-Rong Zhou, Yuan Liu, Xin Dou, Shao-Yue Du, Meng Ding, Wan-Qiu Peng, Shu-Wen Qian, Hai-Yan Huang, Qi-Qun Tang
Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28646531/morin-a-novel-lxr%C3%AE-%C3%AE-dual-antagonist-has-potent-therapeutic-efficacy-for-nonalcoholic-fatty-liver-diseases
#2
Ming Gu, Yu Zhang, Chuhe Liu, Dongshan Wang, Li Feng, Shengjie Fan, Baican Yang, Qingchun Tong, Guang Ji, Cheng Huang
BACKGROUND AND PURPOSE: Morin is a natural occurring flavonoid in many dietary plants and has a wide range of beneficial effects on metabolism; however, the mechanism underlying its action remains elusive. EXPERIMENTAL APPROACH: Reporter assay and the Time-Resolved Fluorescence Resonance Energy Transfer assay were used to identify morin as a dual antagonist of LXRα and LXRβ. High fat-diet mixed with morin (100 mg/100 g diet) was administrated to high-fat diet-induced obese or LXRβ(-/-) mice combining with Western blot and RT-PCR analysis to evaluate the pharmacological effect and mechanism of morin treatment...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646079/identification-of-flavin-containing-monooxygenase-5-fmo5-as-a-regulator-of-glucose-homeostasis-and-a-potential-sensor-of-gut-bacteria
#3
Flora Scott, Sandra G Gonzalez Malagon, Brett A O'Brien, Diede Fennema, Sunil Veeravalli, Clarissa R Coveney, Ian R Phillips, Elizabeth A Shephard
We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic ageing. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (Fmo5(-/-) mice). In comparison with wild-type (WT) counterparts, Fmo5(-/-) mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28641818/the-role-of-kr%C3%A3-ppel-like-factor-14-in-the-pathogenesis-of-atherosclerosis
#4
REVIEW
Wei Xie, Liang Li, Xi-Long Zheng, Wei-Dong Yin, Chao-Ke Tang
The Krüppel-like factor (KLF) family, as the SP/XKLF transcription factors, plays important roles in regulating the expression of genes required for the proper execution of important biological and pathological processes. Recent studies have demonstrated that KLF14, a member of the KLF family, participates in the initiation and progression of atherosclerotic cardiovascular disease (CVD). From the molecular function aspect, this review focuses on the impact of KLF14-mediated regulation in major atherosclerosis-related diseases and pathological processes, such as insulin resistance, type 2 diabetes, dyslipidemia, inflammation, obesity, metabolic syndrome, cell proliferation and differentiation...
June 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28641777/role-of-parl-pink1-parkin-pathway-in-adipocyte-differentiation
#5
Ming-Yuh Shiau, Pin-Shen Lee, Ying-Jyun Huang, Ching-Ping Yang, Chiao-Wan Hsiao, Kai-Yun Chang, Huan-Wen Chen, Yih-Hsin Chang
OBJECTIVE: Adipogenesis determines the number of adipocytes which is increased when individuals become obese. Mitochondria undergo remarkable morphological and functional changes during adipogenesis. PTEN-induced kinase 1 (PINK1) is pivotal to maintain mitochondrial homeostasis in neural cells. The present study aimed at investigating effects of PINK1 on adipogenesis and energy metabolism. METHODS: Expression of presenilin associated rhomboid-like protein (PARL), PINK1 and Parkin, as well as the interaction among these proteins was temporally examined during adipogenesis...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28641547/recent-advances-on-the-role-of-micrornas-in-both-insulin-resistance-and-cancer
#6
Adele Vivacqua, Paola De Marco, Antonino Belfiore, Marcello Maggiolini
BACKGROUND: Insulin resistance is a pathological condition characterized by the failure of target cells to uptake and metabolizes glucose in response to insulin. In particular, the elevated concentrations of glucose, insulin and free insulin growth factor-1, which result from insulin resistance, may generate a pro-inflammatory and pro-tumorigenic state. These alterations may underlie the increased risk to develop various types of cancer as well as the worse cancer prognosis observed in obese and diabetic patients...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28640441/adipose-tissue-derived-omentin-1-function-and-regulation
#7
Takuya Watanabe, Kaho Watanabe-Kominato, Yui Takahashi, Miho Kojima, Rena Watanabe
Omentin-1, also known as intelectin-1, is a recently identified novel adipocytokine of 313 amino acids, which is expressed in visceral (omental and epicardial) fat as well as mesothelial cells, vascular cells, airway goblet cells, small intestine, colon, ovary, and plasma. The level of omentin-1 expression in (pre)adipocytes is decreased by glucose/insulin and stimulated by fibroblast growth factor-21 and dexamethasone. Several lines of experimental evidence have shown that omentin-1 plays crucial roles in the maintenance of body metabolism and insulin sensitivity, and has anti-inflammatory, anti-atherosclerotic, and cardiovascular protective effects via AMP-activated protein kinase/Akt/nuclear factor-κB/mitogen-activated protein kinase (ERK, JNK, and p38) signaling...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28634519/prevalence-and-risk-factors-of-heart-failure-in-the-usa-nhanes-2013-2014-epidemiological-follow-up-study
#8
Saketram Komanduri, Yogesh Jadhao, Sai S Guduru, Pramil Cheriyath, Yijin Wert
Background: Heart Failure (HF) is a progressive epidemic associated with considerable morbidity and mortality. Self-reported data from the National Health and Nutrition Examination Survey (NHANES) provides a unique representation of individuals suffering from HF. The purpose of this study is to analyze updated NHANES 2013-2014 data to identify any changes in the prevalence and current risk factors of HF, especially given the novel lifestyles and increased medical awareness of current generations. Methods: NHANES uses a multistage probability sampling design under the Centers for Disease Control and Prevention (CDC)...
January 2017: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/28634267/30-years-of-the-mineralocorticoid-receptor-the-role-of-the-mineralocorticoid-receptor-in-the-vasculature
#9
REVIEW
Jennifer J DuPont, Iris Z Jaffe
Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed in all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28632765/ctrp3-is-a-novel-biomarker-for-diabetic-retinopathy-and-inhibits-hghl-induced-vcam-1-expression-in-an-ampk-dependent-manner
#10
Zheyi Yan, Jianli Zhao, Lu Gan, Yanqing Zhang, Rui Guo, Xiaoming Cao, Wayne Bond Lau, Xin Ma, Yajing Wang
OBJECTIVES: Diabetic retinopathy (DR) is a severe complication of chronic diabetes. The C1q/TNF-related protein family (CTRPs) has been demonstrated to exert protective effects against obesity and atherosclerosis in animal studies. Heretofore, the association between circulating CTRPs and DR patients has been unexplored. In the current study, we attempt to define this association, as well as the effect of CTRPs upon DR pathophysiology. DESIGN: The present investigation is a case control study that enrolled control subjects and type 2 diabetes mellitus (T2DM) patients diagnosed with DR...
2017: PloS One
https://www.readbyqxmd.com/read/28626527/systematic-data-mining-reveals-synergistic-h3r-mchr1-ligands
#11
David Schaller, Stefanie Hagenow, Gina Alpert, Alexandra Naß, Robert Schulz, Marcel Bermudez, Holger Stark, Gerhard Wolber
In this study, we report a ligand-centric data mining approach that guided the identification of suitable target profiles for treating obesity. The newly developed method is based on identifying target pairs for synergistic positive effects and also encompasses the exclusion of compounds showing a detrimental effect on obesity treatment (off-targets). Ligands with known activity against obesity-relevant targets were compared using fingerprint representations. Similar compounds with activities to different targets were evaluated for the mechanism of action since activation or deactivation of drug targets determines the pharmacological effect...
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28625137/chemokine-like-receptor-1-cmklr-1-receptor-a-potential-therapeutic-target-in-management-of-chemerin-induced-type-2-diabetes-mellitus-and-cancer
#12
Sangeetha Perumalsamy, Nurul Ain Aqilah Mohd Zin, Riyanto Teguh Widodo, Wan Azman Wan Ahmad, Shireene Ratna Db Vethakkan, Hasniza Zaman Huri
BACKGROUND: Chemerin is an adipokine that induces insulin resistance by the mechanism of inflammation in adipose tissue but these are still unclear. A high level of chemerin in humans is considered as a marker of inflammation in insulin resistance and obesity as well as in type 2 diabetes mellitus. Despite the role of chemerin in insulin resistance progression, chemerin as one of the novel adipokines is proposed to be involved in high cancer risk and mortality. AIM: The aim of this paper was to review the role of CMKLR-1 receptor and the potential therapeutic target in the management of chemerin induced type 2 diabetes mellitus and cancer...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28624099/cardiovascular-disease-and-cancer-evidence-for-shared-disease-pathways-and-pharmacologic-prevention
#13
REVIEW
Farzad Masoudkabir, Nizal Sarrafzadegan, Carolyn Gotay, Andrew Ignaszewski, Andrew D Krahn, Margot K Davis, Christopher Franco, Arya Mani
Cardiovascular disease (CVD) and cancer are leading causes of mortality and morbidity worldwide. Strategies to improve their treatment and prevention are global priorities and major focus of World Health Organization's joint prevention programs. Emerging evidence suggests that modifiable risk factors including diet, sedentary lifestyle, obesity and tobacco use are central to the pathogenesis of both diseases and are reflected in common genetic, cellular, and signaling mechanisms. Understanding this important biological overlap is critical and may help identify novel therapeutic and preventative strategies for both disorders...
June 2, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28622524/ampk-mechanisms-of-cellular-energy-sensing-and-restoration-of-metabolic-balance
#14
REVIEW
Daniel Garcia, Reuben J Shaw
AMPK is a highly conserved master regulator of metabolism, which restores energy balance during metabolic stress both at the cellular and physiological levels. The identification of numerous AMPK targets has helped explain how AMPK restores energy homeostasis. Recent advancements illustrate novel mechanisms of AMPK regulation, including changes in subcellular localization and phosphorylation by non-canonical upstream kinases. Notably, the therapeutic potential of AMPK is widely recognized and heavily pursued for treatment of metabolic diseases such as diabetes, but also obesity, inflammation, and cancer...
June 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28615690/cathepsin-d-regulates-lipid-metabolism-in-murine-steatohepatitis
#15
Tom Houben, Yvonne Oligschlaeger, Tim Hendrikx, Albert V Bitorina, Sofie M A Walenbergh, Patrick J van Gorp, Marion J J Gijbels, Silvia Friedrichs, Jogchum Plat, Frank G Schaap, Dieter Lütjohann, Marten H Hofker, Ronit Shiri-Sverdlov
Due to the obesity epidemic, non-alcoholic steatohepatitis (NASH) is a prevalent liver disease, characterized by fat accumulation and inflammation of the liver. However, due to a lack of mechanistic insight, diagnostic and therapeutic options for NASH are poor. Recent evidence has indicated cathepsin D (CTSD), a lysosomal enzyme, as a marker for NASH. Here, we investigated the function of CTSD in NASH by using an in vivo and in vitro model. In addition to diminished hepatic inflammation, inhibition of CTSD activity dramatically improved lipid metabolism, as demonstrated by decreased plasma and liver levels of both cholesterol and triglycerides...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606411/can-parasitic-worms-cure-the-modern-world-s-ills
#16
REVIEW
Margaret M Harnett, William Harnett
There has been increasing recognition that the alarming surge in allergy and autoimmunity in the industrialised and developing worlds shadows the rapid eradication of pathogens, such as parasitic helminths. Appreciation of this has fuelled an explosion in research investigating the therapeutic potential of these worms. This review considers the current state-of-play with a particular focus on exciting recent advances in the identification of potential novel targets for immunomodulation that can be exploited therapeutically...
June 9, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28602634/dp1-receptor-agonist-bw245c-inhibits-diet-induced-obesity-in-apoe-mice
#17
Sunil Kumar, Thomas Palaia, Christopher Hall, Louis Ragolia
BACKGROUND/OBJECTIVE: Lipocalin Prostaglandin D2 synthase (LPGDS) contributes to the production of PGD2, which has been associated with adipogenesis. In this study, we aimed to investigate the role of PGD2 on obesity through its DP1 and DP2 receptor signaling using intraperitoneal injection of their respective agonists and antagonists. METHODS: ApoE(-/-) mice were divided into five groups: vehicle control (n=5), DP1 receptor agonist (n=5), DP1 receptor antagonist (n=5), DP2 receptor agonist (n=5), and DP2 receptor antagonist (n=5), and the study was carried out for 10 weeks...
June 8, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28602160/kahweol-inhibits-lipid-accumulation-and-induces-glucose-uptake-through-activation-of-amp-activated-protein-kinase-ampk
#18
Jung-Hwan Baek, Nam-Jun Kim, Jun-Kyu Song, Kyung-Hee Chun
Weight loss ≥5% is sufficient to significantly reduce health risks for people with obesity; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with anti-adipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of Phosphorylated AKT and phosphorylated JAK2, which induce lipid accumulation, decreased in kahweol-treated cells...
June 12, 2017: BMB Reports
https://www.readbyqxmd.com/read/28595552/pigment-epithelium-derived-factor-a-novel-therapeutic-target-for-cardiometabolic-diseases-and-related-complications
#19
Sho-Ichi Yamagishi, Takanori Matsui
Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert anti-thrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications...
June 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28593550/yh18421-a-novel-gpr119-agonist-exerts-sustained-glucose-lowering-and-weight-loss-in-diabetic-mouse-model
#20
Yoo Hoi Park, Hyun Ho Choi, Dong Hoon Lee, Soo Yong Chung, Na Yeon Yang, Do Hoon Kim, Mi Kyeong Ju, Tae Dong Han, Su Youn Nam, Kyu-Won Kim
G-protein-coupled receptor 119 (GPR119) represents a promising target for the treatment of type 2 diabetes as it can increase both GLP-1 secretion from intestinal L cells and glucose-stimulated insulin secretion (GSIS) from pancreatic β cells. Due to this dual mechanism of action, the development of small molecule GPR119 agonists has received much interest for the treatment of type 2 diabetes. Here, we identified a novel small-molecule GPR119 agonist, YH18421 and evaluated its therapeutic potential. YH18421 specifically activated human GPR119 with high potency and potentiated GLP-1 secretion and GSIS in vitro cell based systems...
June 8, 2017: Archives of Pharmacal Research
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