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AdipoRon

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https://www.readbyqxmd.com/read/29704399/design-synthesis-chalcone-derivatives-as-adipor-agonist-for-type-2-diabetes
#1
Panhu Zhu, Weijun Huang, Jiaming Li, Xiaodong Ma, Mengqi Hu, Yujun Wang, Qinlong Xu, Xianna Wang
Two structurally novel series of chalcone derivatives were designed and synthesized as potential agents against type 2 diabetes. As a result of the antidiabetic biological evaluation in streptozotocin (STZ)-induced type 2 diabetes animal model, 13e, 13g, and 19f showed more significant reduction in serum Glu, TG, TC levels by contrast to the positive control AdipoRon. In addition to upregulating the expression of AdipoR1 and AdipoR2, 13e and 19f treatment also increased expression of AMPK and PPAR-α. Taken together, these results suggested that 13e and 19f might be a promising compound for type 2 diabetes treatment...
April 28, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29462574/adiponectin-receptor-agonist-adiporon-decreased-ceramide-and-lipotoxicity-and-ameliorated-diabetic-nephropathy
#2
Sun Ryoung Choi, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Yaeni Kim, Beom Soon Choi, Yong-Soo Kim, Hye Won Kim, Kyung-Min Lim, Min Jeong Kim, Cheol Whee Park
BACKGROUND: Adiponectin is known to take part in the regulation of energy metabolism. AdipoRon, an orally-active synthetic adiponectin agonist, binds to both adiponectin receptors (AdipoR)1/R2 and ameliorates diabetic complications. Among the lipid metabolites, the ceramide subspecies of sphingolipids have been linked to features of lipotoxicity, including inflammation, cell death, and insulin resistance. We investigated the role of AdipoRon in the prevention and development of type 2 diabetic nephropathy...
February 17, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29377113/lga-newborn-from-patients-with-pregestational-obesity-present-reduced-adiponectin-mediated-vascular-relaxation-and-endothelial-dysfunction-in-fetoplacental-arteries
#3
E C Muñoz-Muñoz, B J Krause, R Uauy, P Casanello
Maternal obesity is associated with large-for-gestational-age (LGA) neonates and programming of obesity-related cardiovascular disease in the offspring, however, the mechanisms that lead to the later are unclear. Presently, interpretations of NO-dependent changes in vascular function in LGA newborn from obese mothers are conflicting. Adiponectin improves endothelial function by increasing eNOS activity and NO production. We propose that LGAs from obese mothers present a diminished vascular response to adiponectin; thus, affecting eNOS and AMPK activation...
January 27, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29330340/the-adiponectin-receptor-agonist-adiporon-ameliorates-diabetic-nephropathy-in-a-model-of-type-2-diabetes
#4
Yaeni Kim, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Hye Eun Yoon, Seok Joon Shin, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Cheol Whee Park
Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor- α (PPAR α ) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes...
April 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29180355/photoreceptor-glucose-metabolism-determines-normal-retinal-vascular-growth
#5
Zhongjie Fu, Chatarina A Löfqvist, Raffael Liegl, Zhongxiao Wang, Ye Sun, Yan Gong, Chi-Hsiu Liu, Steven S Meng, Samuel B Burnim, Ivana Arellano, My T Chouinard, Rubi Duran, Alexander Poblete, Steve S Cho, James D Akula, Michael Kinter, David Ley, Ingrid Hansen Pupp, Saswata Talukdar, Ann Hellström, Lois Eh Smith
The neural cells and factors determining normal vascular growth are not well defined even though vision-threatening neovessel growth, a major cause of blindness in retinopathy of prematurity (ROP) (and diabetic retinopathy), is driven by delayed normal vascular growth. We here examined whether hyperglycemia and low adiponectin (APN) levels delayed normal retinal vascularization, driven primarily by dysregulated photoreceptor metabolism. In premature infants, low APN levels correlated with hyperglycemia and delayed retinal vascular formation...
January 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29156726/adiponectin-receptor-agonists-inhibit-leptin-induced-pstat3-and-in-vivo-pancreatic-tumor-growth
#6
Fanuel Messaggio, Alisha M Mendonsa, Jason Castellanos, Nagaraj S Nagathihalli, Lee Gorden, Nipun B Merchant, Michael N VanSaun
Obesity is a significant risk factor for pancreatic cancer, harboring a chronic inflammatory condition characterized by dysregulation of the adipokines, leptin and adiponectin, that in turn alter oncogenic signaling pathways. We and others have shown that leptin promotes the proliferation and an invasive potential of pancreatic cancer cells through STAT3 mediated signaling. However, the role of adiponectin on the tumorigenicity of pancreatic cancer has not been elucidated. Adiponectin represents an important negative regulator of cytokines, which acts through two receptors, ADIPOR1 and ADIPOR2, to elicit pro-apoptotic, anti-inflammatory, and anti-angiogenic responses...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29115432/adiponectin-and-its-receptors-are-involved-in-hypertensive-vascular-injury
#7
Ruimin Guo, Min Han, Juan Song, Jun Liu, Yanni Sun
Adipocyte-derived adiponectin (APN) is involved in the protection against cardiovascular disease, but the endogenous APN and its receptor expression in the perivascular adipocytes and their role in hypertensive vascular injury remain unclear. The present study aimed to detect endogenous APN and its receptor expression and their protective effects against hypertensive vascular injury. APN was mainly expressed in the perivascular adipocytes, while its receptors AdipoR1 and AdipoR2 were ubiquitously expressed in the blood vessels...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901521/adiponectin-receptor-agonist-adiporon-suppresses-adipogenesis-in-c3h10t1-2-cells-through-the-adenosine-monophosphate%C3%A2-activated-protein-kinase-signaling-pathway
#8
Shu-Juan Wang, Wen-Yi Lu, Kai-Yan Liu
The aim of the present study was to investigate the effects of AdipoRon, an adiponectin receptor agonist, on adipogenesis in C3H10T1/2 cells and to explore the underlying mechanisms. C3H10T1/2 cells were treated with increasing doses of AdipoRon for 8 days, and Oil Red O staining was used to assess lipid accumulation. The protein and mRNA expression levels of adipogenic transcription factors and adipocyte‑specific genes were examined by western blotting and reverse transcription quantitative polymerase chain reaction, respectively...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28825851/restoring-diabetes-induced-autophagic-flux-arrest-in-ischemic-reperfused-heart-by-adipor-adiponectin-receptor-activation-involves-both-ampk-dependent-and-ampk-independent-signaling
#9
Yajing Wang, Bin Liang, Wayne Bond Lau, Yunhui Du, Rui Guo, Zheyi Yan, Lu Gan, Wenjun Yan, Jianli Zhao, Erhe Gao, Walter Koch, Xin-Liang Ma
Macroautophagy/autophagy is increasingly recognized as an important regulator of myocardial ischemia-reperfusion (MI-R) injury. However, whether and how diabetes may alter autophagy in response to MI-R remains unknown. Deficiency of ADIPOQ, a cardioprotective molecule, markedly increases MI-R injury. However, the role of diabetic hypoadiponectinemia in cardiac autophagy alteration after MI-R is unclear. Utilizing normal control (NC), high-fat-diet-induced diabetes, and Adipoq knockout (adipoq-/- ) mice, we demonstrated that autophagosome formation was modestly inhibited and autophagosome clearance was markedly impaired in the diabetic heart subjected to MI-R...
2017: Autophagy
https://www.readbyqxmd.com/read/28593738/sex-differences-in-the-regulation-of-porcine-coronary-artery-tone-by-perivascular-adipose-tissue-a-role-of-adiponectin
#10
Abdulla A Ahmad, Michael D Randall, Richard E Roberts
BACKGROUND AND PURPOSE: As there is sexual dimorphism in the regulation of vascular tone, the aim of this present study was to determine whether there are sex differences in perivascular adipose tissue (PVAT)-mediated regulation of the porcine coronary artery (PCA) tone. EXPERIMENTAL APPROACH: Isometric tension recording system was used to record changes in tone in PCAs. Western blot analysis was performed to examine the expression of adiponectin in PVAT and adiponectin receptors and adiponectin binding protein (APPL1) in PCA...
August 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28546220/activation-of-adiponectin-receptor-regulates-proprotein-convertase-subtilisin-kexin-type-9-expression-and-inhibits-lesions-in-apoe-deficient-mice
#11
Lei Sun, Xiaoxiao Yang, Qi Li, Peng Zeng, Ying Liu, Lipei Liu, Yuanli Chen, Miao Yu, Chuanrui Ma, Xiaoju Li, Yan Li, Rongxin Zhang, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
OBJECTIVE: The reduced adiponectin levels are associated with atherosclerosis. Adiponectin exerts its functions by activating adiponectin receptor (AdipoR). Proprotein convertase subtilisin kexin type 9 (PCSK9) degrades LDLR protein (low-density lipoprotein receptor) to increase serum LDL-cholesterol levels. PCSK9 expression can be regulated by PPARγ (peroxisome proliferator-activated receptor γ) or SREBP2 (sterol regulatory element-binding protein 2). The effects of AdipoR agonists on PCSK9 and LDLR expression, serum lipid profiles, and atherosclerosis remain unknown...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28293385/adiporon-may-be-benefit-for-atherosclerosis-prevention
#12
EDITORIAL
Maryam Esfahani, Nooshin Shabab, Massoud Saidijam
Atherosclerosis has serious role in coronary arteries disease, so it is important to establish effective strategies for prevention or even treatment of atherosclerosis. Adiponectin, as one of the most abundant adipokines, has insulin sensitivity, anti-inflammatory and anti-atherogenic properties. Disturbed adiponectin actions through its receptor, (AdipoR1 and AdipoR2) may be involved in atherosclerosis development. Some adiponectin effects are mediated by AMPK and PPAR-α signaling. AdipoRon is an orally active synthetic molecule which can bind to AdipoR1, Adipo R2 and activate them...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28237515/adiporon-an-adiponectin-receptor-agonist-attenuates-pdgf-induced-vsmc-proliferation-through-inhibition-of-mtor-signaling-independent-of-ampk-implications-toward-suppression-of-neointimal-hyperplasia
#13
Arwa Fairaq, Noha M Shawky, Islam Osman, Prahalathan Pichavaram, Lakshman Segar
Hypoadiponectinemia is associated with an increased risk of coronary artery disease. Although adiponectin replenishment mitigates neointimal hyperplasia and atherosclerosis in mouse models, adiponectin therapy has been hampered in a clinical setting due to its large molecular size. Recent studies demonstrate that AdipoRon (a small-molecule adiponectin receptor agonist) improves glycemic control in type 2 diabetic mice and attenuates postischemic cardiac injury in adiponectin-deficient mice, in part, through activation of AMP-activated protein kinase (AMPK)...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28187508/the-role-of-adiponectin-receptors-in-the-regulation-of-synaptic-transmission-in-the-hippocampus
#14
Filippo Weisz, Sonia Piccinin, Dalila Mango, Richard Teke Ngomba, Nicola B Mercuri, Ferdinando Nicoletti, Robert Nisticò
In the last two decades adiponectin, member of the adipokines family, gained attention because of its unique antidiabetic effects. However, the presence in the brain of adiponectin receptors and adiponectin itself raised interest because of the possible association with neuropsychiatric diseases. Indeed, clinical studies found altered concentration of adiponectin both in plasma and cerebrospinal fluid in several pathologies including depression, multiple sclerosis, Alzheimer's disease and stroke. Moreover, recent preclinical studies also suggest its involvement in different physiological functions...
May 2017: Synapse
https://www.readbyqxmd.com/read/27627895/promigratory-and-proangiogenic-effects-of-adiporon-on-bone-marrow-derived-mesenchymal-stem-cells-an-in-vitro-study
#15
Sara Malih, Massoud Saidijam, Kamran Mansouri, Mona Pourjafar, Maryam Sadat Tafakh, Fahimeh Talebzadeh, Rezvan Najafi
OBJECTIVES: To investigate the effect of AdipoRon on major factors involved in survival, migration and neovascularization of rat bone marrow-derived mesenchymal stem cells. RESULTS: AdipoRon promoted the MSCs viability. Real-time PCR indicated that the expression of cyclooxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1) C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 2 (CCR2), vascular endothelial growth factor matrix metalloproteinase-2 (MMP-2) and MMP-9 were upregulated in AdipoRon-treated MSCs compared to control groups...
January 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/27516150/hepatoprotective-effects-of-adiporon-against-d-galactosamine-induced-liver-injury-in-mice
#16
Ying Wang, Yumeng Wan, Guihong Ye, Pu Wang, Xiaowen Xue, Guanzhong Wu, Boping Ye
Adiponectin is an antidiabetic and antiatherogenic adipokine, which plays distinct roles in the balance of energy homoeostasis. As an insulin sensitizing hormone, adiponectin exerts multiple biological effects by the specific receptors (AdipoR1 and AdipoR2), through activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)α pathways. AdipoRon, an orally active synthetic small-molecule AdipoR agonist, shows very similar effects to adiponectin in vitro and in vivo, which could be a promising therapeutic approach for obesity-related disorders...
October 10, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27137743/adiponectin-regulates-contextual-fear-extinction-and-intrinsic-excitability-of-dentate-gyrus-granule-neurons-through-adipor2-receptors
#17
D Zhang, X Wang, B Wang, J C Garza, X Fang, J Wang, P E Scherer, R Brenner, W Zhang, X-Y Lu
Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear expression and impaired fear extinction. The underlying molecular and cellular mechanisms of PTSD are largely unknown. The current pharmacological and non-pharmacological treatments for PTSD are either ineffective or temporary with high relapse rates. Here we report that adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning. Infusions of adiponectin into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear...
July 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27003122/identification-and-characterization-of-in-vitro-and-in-vivo-generated-metabolites-of-the-adiponectin-receptor-agonists-adiporon-and-112254
#18
Josef Dib, Andreas Thomas, Philippe Delahaut, Eric Fichant, Wilhelm Schänzer, Mario Thevis
Peroxisome proliferator-activated receptors (PPARs), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) are regulators of transcriptional processes and effects of exercise and pseudo-exercise situations. Compounds occasionally referred to as endurance exercise mimetics such as AdipoRon and 112254, both adiponectin receptor agonists, can be used to simulate the physiology of endurance exercise via pathways including these transcriptional regulators...
June 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/26282004/adiporon-a-possible-drug-for-colorectal-cancer-prevention
#19
EDITORIAL
Sara Malih, Rezvan Najafi
Colorectal cancer (CRC) is in the third place of the most common cancers. Certain risk factors can increase the development of CRC, including diet and inheritance. Several studies have shown that there is a potential link between obesity and CRC. Adipose tissue is known to be a largest endocrine organ in the body, with the ability to produce various cytokines including adiponectin. Two types of adiponectin receptor, AdipoR1 and AdipoR2, have been detected in various cancer tissues such as CRC. There is mounting evidence that AdipoR1 signaling occurs mainly through 5' AMP-activated protein kinase (AMPK) and adiponectin inhibits colorectal cancer cell growth via activation of AMPK, thereby suppression of the mammalian target of rapamycin (mTOR) pathway...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26037251/adiporon-the-first-orally-active-adiponectin-receptor-activator-attenuates-postischemic-myocardial-apoptosis-through-both-ampk-mediated-and-ampk-independent-signalings
#20
Yanqing Zhang, Jianli Zhao, Rui Li, Wayne Bond Lau, Yue-Xing Yuan, Bin Liang, Rong Li, Er-He Gao, Walter J Koch, Xin-Liang Ma, Ya-Jing Wang
Adiponectin (APN) is a cardioprotective molecule. Its reduction in diabetes exacerbates myocardial ischemia/reperfusion (MI/R) injury. Although APN administration in animals attenuates MI/R injury, multiple factors limit its clinical application. The current study investigated whether AdipoRon, the first orally active molecule that binds APN receptors, may protect the heart against MI/R injury, and if so, to delineate the involved mechanisms. Wild-type (WT), APN knockout (APN-KO), and cardiomyocyte specific-AMPK dominant negative (AMPK-DN) mice were treated with vehicle or AdipoRon (50 mg/kg, 10 min prior to MI) and subjected to MI/R (30 min/3-24 h)...
August 1, 2015: American Journal of Physiology. Endocrinology and Metabolism
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