{"title":"Endocannabinoids and obesity development – the adipose tissue","authors":"Enzo Nisoli","doi":"10.1016/j.ddmec.2010.12.002","DOIUrl":"10.1016/j.ddmec.2010.12.002","url":null,"abstract":"<div><p><span>The adipose tissue is an endocrine organ with a key role in energy metabolism. The expansion of body fat (particularly of visceral fat) contributes to the increased cardiovascular risk of obese individuals. Obesity and its metabolic complications are characterized by fat inflammation and by an overactive endocannabinoid (EC) system. Chronic treatment with cannabinoid receptor<span><span> type 1 (CB1R) antagonists leads to weight loss and improved cardiometabolic risk profile in obese rodents and humans. EC overactivity is a cause of mitochondrial dysfunction, which may trigger </span>endoplasmic reticulum stress in adipocytes and metabolically active organs, thus significantly contributing to the pathogenesis and progression of obesity. Among the major pathways involved in these processes, the nitric oxide-generating system and the </span></span>p38 MAPK pathways might be targets for the development of anti-obesity drugs. Peripheral CB1Rs, and possibly CB2Rs, also play significant roles in obesity and diabetes. Together, these findings support the concept that dietary/lifestyle interventions and pharmacologic compounds, able to attenuate EC overactivity in adipose and other metabolically active tissues, may be useful for the treatment of human obesity and related disorders.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 3","pages":"Pages e199-e204"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.12.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73263680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pasqua Dipasquale , Adele Romano , Silvia Cianci, Laura Righetti, Silvana Gaetani
{"title":"Oleoylethanolamide: a new player in energy metabolism control. Role in food intake","authors":"Pasqua Dipasquale , Adele Romano , Silvia Cianci, Laura Righetti, Silvana Gaetani","doi":"10.1016/j.ddmec.2011.01.004","DOIUrl":"10.1016/j.ddmec.2011.01.004","url":null,"abstract":"<div><p>Oleoylethanolamide<span> (OEA) is a lipid amide produced by enterocytes upon the absorption of dietary fat and participates in the induction of satiety. Through indirect pathways, probably depending on the local activation of peroxisome-proliferator-activated receptor-alpha and involving afferent vagus nerve fibers, OEA signal is transmitted to the brain-stem and the hypothalamus, where it stimulates the release of oxytocin from magnocellular neurons.</span></p><p>OEA mechanism might, thus, provide a novel target for the design of therapies controlling appetite.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 3","pages":"Pages e169-e174"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2011.01.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82690450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endocannabinoids in the pathophysiology of obesity – The liver","authors":"Ariane Mallat , Sophie Lotersztajn","doi":"10.1016/j.ddmec.2010.11.001","DOIUrl":"10.1016/j.ddmec.2010.11.001","url":null,"abstract":"<div><p><span>With the increasing prevalence of obesity and co-morbidities, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of liver disease in Western countries. Clinical and experimental studies have identified CB1 and CB2 receptors as potential novel therapeutic targets in the management of NAFLD. CB2 receptors in the adipose tissue probably participate in the pathogenesis of obesity-associated insulin resistance and non-alcoholic fatty liver disease. However, hepatic CB2 receptors display beneficial effects in various aspects of liver disease, including liver injury, regeneration and fibrosis. Hence, additional </span>preclinical studies<span> are warranted to define the contribution of adipose tissue versus liver CB2 receptors during chronic liver diseases. Although the development of CB1 antagonists has recently been suspended due to an alarming rate of mood disorders, preliminary preclinical data obtained with peripheral CB1 antagonists give real hopes in the development of active CB1 molecules devoid of central adverse effects.</span></p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 3","pages":"Pages e185-e190"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74368272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of phospholipase A2-derived mediators in obesity","authors":"Marcia J. Abbott, Tianyi Tang, Hei Sook Sul","doi":"10.1016/j.ddmec.2011.01.003","DOIUrl":"10.1016/j.ddmec.2011.01.003","url":null,"abstract":"<div><p><span>Obesity has become an epidemic and its prevalence is increasing exponentially. A great deal of focus has been given to understanding the molecular processes that regulate obesity. The characterization of phospholipase A</span><sub>2</sub>s, especially adipose-specific PLA<sub>2</sub>, has lead to a proposed role of their downstream products in the progression of obesity and obesity related disorders. This review summarizes recent developments in the role of PLA<sub>2</sub><span> and their downstream effects in the development of metabolic disorders.</span></p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 3","pages":"Pages e213-e218"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2011.01.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40101154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endocannabinoids in the aetiopathology of obesity – Central mechanisms","authors":"Tim C. Kirkham, Elizabeth K. Rogers","doi":"10.1016/j.ddmec.2010.12.003","DOIUrl":"10.1016/j.ddmec.2010.12.003","url":null,"abstract":"<div><p><span>The principal contributing factor to obesity is overconsumption of palatable, energy-dense foods. Such foods engender appetite, even in the face of sufficiency, and their hedonic properties promote overeating. Research points to endocannabinoids being key factors in motivational circuits that assign incentive and reward value to food, with cannabinoid CB</span><sub>1</sub> receptor agonists enhancing hunger, food anticipation and food palatability. Endocannabinoid involvement in food ‘wanting’ and ‘liking’, and possible endocannabinoid-based obesity therapies are discussed.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 3","pages":"Pages e163-e168"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.12.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82362496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Palmitoylethanolamide, adipocytes and obesity-related inflammatory states","authors":"Laurence Hoareau, Régis Roche","doi":"10.1016/j.ddmec.2011.01.002","DOIUrl":"10.1016/j.ddmec.2011.01.002","url":null,"abstract":"<div><p>Obesity is characterized by ‘low grade’ and chronic inflammation<span><span>, which leads to pathologies such as insulin resistance, type 2 diabetes or </span>atherosclerosis. The role of the adipose tissue, and specifically adipocytes, in this process is discussed.</span></p><p>Besides, the palmitoylethanolamide (PEA), an endocannabinoid-like molecule, was revealed to have an overall anti-inflammatory effect; moreover, it is secreted by adipose tissue. Thus, this review aims to understand the role of PEA in adipocytes in the case of obesity-related inflammatory states.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 3","pages":"Pages e205-e212"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2011.01.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79519120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Highly specific modulators of protein kinase C localization: applications to heart failure","authors":"Nir Qvit, Daria Mochly-Rosen","doi":"10.1016/j.ddmec.2010.07.001","DOIUrl":"10.1016/j.ddmec.2010.07.001","url":null,"abstract":"<div><p><span>Heart failure (HF) in which the blood supply does not match the body's needs, affects 10% of the population over 65 years old. The </span>protein kinase C (PKC) family of kinases has a key role in normal and disease states. Here we discuss the role of PKC in HF and focus on the use of specific PKC regulators to identify the mechanism leading to this pathology and potential leads for therapeutics.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 2","pages":"Pages e87-e93"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29530272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ca2+/calmodulin-dependent protein kinase II in heart failure","authors":"Howard Schulman , Mark E. Anderson","doi":"10.1016/j.ddmec.2010.07.005","DOIUrl":"10.1016/j.ddmec.2010.07.005","url":null,"abstract":"<div><p>Ca<sup>2+</sup>/calmodulin (CaM)-dependent protein kinase II (CaMKII) is now recognized to play a central role in myocardial biology and disease. CaMKII appears to grade myocardial performance and regulate heart rate by catalyzing the phosphorylation of major proteins involved in cardiac excitation-contraction coupling. Under pathological stress, CaMKII activates hypertrophic and inflammatory transcriptional pathways and promotes apoptosis. Animal studies suggest that CaMKII inhibition may be an effective approach for treating common forms of structural heart disease.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 2","pages":"Pages e117-e122"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.07.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29824320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Changwon Kho, Ahyoung Lee, Dongtak Jeong, Roger J. Hajjar
{"title":"Refilling intracellular calcium stores","authors":"Changwon Kho, Ahyoung Lee, Dongtak Jeong, Roger J. Hajjar","doi":"10.1016/j.ddmec.2010.08.004","DOIUrl":"10.1016/j.ddmec.2010.08.004","url":null,"abstract":"<div><p><span>Within the cardiac cell, the movements of calcium ions<span> are tightly regulated by a number of regulatory proteins including pumps, and channels. The sarcoplasmic reticulum (SR) is in large part responsible for orchestrating these movements for the normal functioning of the cardiomyocyte. Alterations of SR regulatory proteins in failing hearts lead to abnormal Ca</span></span><sup>2+</sup><span> homeostasis and consequently to a deficient contractile state. This review focuses on the roles of SR Ca</span><sup>2+</sup> regulators in disease states and novel strategies for therapeutic targeting of these pathways.</p></div>","PeriodicalId":72843,"journal":{"name":"Drug discovery today. Disease mechanisms","volume":"7 2","pages":"Pages e145-e150"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ddmec.2010.08.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29545815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}