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Xavier", "lastName": "Pi-Sunyer" }, { "creatorType": "author", "firstName": "Jane M.", "lastName": "Johnston" }, { "creatorType": "author", "firstName": "Shi D.", "lastName": "Yan" }, { "creatorType": "author", "firstName": "Nikolaos", "lastName": "Tezapsidis" } ], "abstractNote": "Aβ peptide is the major proteinateous component of the amyloid plaques found in the brains of Alzheimer’s disease (AD) patients and is regarded by many as the culprit of the disorder. It is well documented that brain lipids are intricately involved in Aβ-related pathogenic pathways. An important modulator of lipid homeostasis is the pluripotent peptide leptin. Here we demonstrate leptin’s ability to modify Aβ levels in vitro and in vivo. Similar to methyl-β-cyclodextrin, leptin reduces β-secretase activity in neuronal cells possibly by altering the lipid composition of membrane lipid rafts. This phenotype contrasts treatments with cholesterol and etomoxir, an inhibitor of carnitine-palmitoyl transferase-1. Conversely, inhibitors of acetyl CoA carboxylase and fatty acid synthase mimicked leptin’s action. Leptin was also able to increase apoE-dependent Aβ uptake in vitro. Thus, leptin can modulate bidirectional Aβ kinesis, reducing its levels extracellularly. Most strikingly, chronic administration of leptin to AD-transgenic animals reduced the brain Aβ load, underlying its therapeutic potential.—Fewlass, D. C., Noboa, K., Pi-Sunyer, F. X., Johnston, J. M., Yan, S. D., Tezapsidis, N. Obesity-related leptin regulates Alzheimer’s Aβ.", "publicationTitle": "The FASEB Journal", "publisher": "", "place": "", "date": "12/01/2004", "volume": "18", "issue": "15", "section": "", "partNumber": "", "partTitle": "", "pages": "1870-1878", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "FASEB J", "DOI": "10.1096/fj.04-2572com", "citationKey": "", "url": "http://www.fasebj.org/content/18/15/1870", "accessDate": "2013-05-07T02:34:05Z", "PMID": "", "PMCID": "", "ISSN": "0892-6638, 1530-6860", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "en", "libraryCatalog": "www.fasebj.org", "callNumber": "", "rights": "", "extra": "PMID: 15576490", "tags": [ { "tag": "AD", "type": 1 }, { "tag": "Aβ production", "type": 1 }, { "tag": "leptin signaling", "type": 1 } ], "collections": [ "J3P8Q9HT" ], "relations": {}, "dateAdded": "2013-05-07T02:34:05Z", "dateModified": "2013-05-07T02:34:05Z" } }, { "key": "QWQS4755", "version": 18, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/QWQS4755", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/QWQS4755", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/3MMDHABT", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "QWQS4755", "version": 18, "parentItem": "3MMDHABT", "itemType": "attachment", "linkMode": "imported_url", "title": "PubMed Central Full Text PDF", "accessDate": "2013-05-07T02:32:24Z", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083858/pdf/nihms-287984.pdf", "note": "", "contentType": "application/pdf", "charset": "", "filename": "Patel et al. - 2008 - Caveolae as Organizers of Pharmacologically Releva.pdf", "md5": "a0d55597f23e2410fde71e869b70b906", "mtime": 1367893945399, "tags": [], "relations": {}, "dateAdded": "2013-05-07T02:32:24Z", "dateModified": "2013-05-07T02:32:26Z" } }, { "key": "TJRAEKVX", "version": 17, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/TJRAEKVX", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/TJRAEKVX", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/3MMDHABT", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } } }, "data": { "key": "TJRAEKVX", "version": 17, "parentItem": "3MMDHABT", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed Central Link", "accessDate": "2013-05-07T02:32:24Z", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083858/", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-05-07T02:32:24Z", "dateModified": "2013-05-07T02:32:24Z" } }, { "key": "3MMDHABT", "version": 17, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/3MMDHABT", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/3MMDHABT", "type": "text/html" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "creatorSummary": "Patel et al.", "parsedDate": "2008", "numChildren": 2 }, "data": { "key": "3MMDHABT", "version": 17, "itemType": "journalArticle", "title": "Caveolae as Organizers of Pharmacologically Relevant Signal Transduction Molecules", "creators": [ { "creatorType": "author", "firstName": "Hemal H.", "lastName": "Patel" }, { "creatorType": "author", "firstName": "Fiona", "lastName": "Murray" }, { "creatorType": "author", "firstName": "Paul A.", "lastName": "Insel" } ], "abstractNote": "Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations of the plasma membrane that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N and C termini, palmitolylation sites, and a scaffolding domain that facilitates interaction and organization of signaling molecules so as to help provide coordinated and efficient signal transduction. Such signaling components include upstream entities (e.g., G protein–coupled receptors (GPCRs), receptor tyrosine kinases, and steroid hormone receptors) and downstream components (e.g., heterotrimeric and low-molecular-weight G proteins, effector enzymes, and ion channels). Diseases associated with aberrant signaling may result in altered localization or expression of signaling proteins in caveolae. Caveolin-knockout mice have numerous abnormalities, some of which may reflect the impact of total body knockout throughout the life span. This review provides a general overview of caveolins and caveolae, signaling molecules that localize to caveolae, the role of caveolae/caveolin in cardiac and pulmonary pathophysiology, pharmacologic implications of caveolar localization of signaling molecules, and the possibility that caveolae might serve as a therapeutic target.", "publicationTitle": "Annual review of pharmacology and toxicology", "publisher": "", "place": "", "date": "2008", "volume": "48", "issue": "", "section": "", "partNumber": "", "partTitle": "", "pages": "359-391", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Annu Rev Pharmacol Toxicol", "DOI": "10.1146/annurev.pharmtox.48.121506.124841", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083858/", "accessDate": "2013-05-07T02:32:24Z", "PMID": "", "PMCID": "", "ISSN": "0362-1642", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: 17914930\nPMCID: PMC3083858", "tags": [], "collections": [ "J3P8Q9HT" ], "relations": {}, "dateAdded": "2013-05-07T02:32:24Z", "dateModified": "2013-05-07T02:32:24Z" } }, { "key": "ET95QS3D", "version": 18, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/ET95QS3D", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/ET95QS3D", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/5Z65K9W6", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "ET95QS3D", "version": 18, "parentItem": "5Z65K9W6", "itemType": "attachment", "linkMode": "imported_url", "title": "Full Text PDF", "accessDate": "2013-05-07T02:31:22Z", "url": "http://bloodjournal.hematologylibrary.org/content/109/4/1515.full.pdf", "note": "", "contentType": "application/pdf", "charset": "", "filename": "Song et al. - 2007 - Caveolin-1 regulates expression of junction-associ.pdf", "md5": "6af4671ec0f4be0c5b1122704b97b62f", "mtime": 1367893899059, "tags": [], "relations": {}, "dateAdded": "2013-05-07T02:31:22Z", "dateModified": "2013-05-07T02:31:39Z" } }, { "key": "8GHPI32E", "version": 18, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/8GHPI32E", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/8GHPI32E", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/5Z65K9W6", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } } }, "data": { "key": "8GHPI32E", "version": 18, "parentItem": "5Z65K9W6", "itemType": "attachment", "linkMode": "imported_url", "title": "Snapshot", "accessDate": "2013-05-07T02:31:22Z", "url": "http://bloodjournal.hematologylibrary.org/content/109/4/1515.abstract", "note": "", "contentType": "text/html", "charset": "utf-8", "filename": "1515.html", "md5": "9364e3e582568cb10061b5ea1a04dd5d", "mtime": 1367893883710, "tags": [], "relations": {}, "dateAdded": "2013-05-07T02:31:22Z", "dateModified": "2013-05-07T02:31:22Z" } }, { "key": "5Z65K9W6", "version": 16, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/5Z65K9W6", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/5Z65K9W6", "type": "text/html" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "creatorSummary": "Song et al.", "parsedDate": "2007-02-15", "numChildren": 3 }, "data": { "key": "5Z65K9W6", "version": 16, "itemType": "journalArticle", "title": "Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells", "creators": [ { "creatorType": "author", "firstName": "Li", "lastName": "Song" }, { "creatorType": "author", "firstName": "Shujun", "lastName": "Ge" }, { "creatorType": "author", "firstName": "Joel S.", "lastName": "Pachter" } ], "abstractNote": "Recent evidence from this laboratory indicated that reduced expression of caveolin-1 accompanied the diminished expression of tight junction (TJ)–associated proteins occludin and zonula occludens-1 (ZO-1) following stimulation of brain microvascular endothelial cells (BMECs) with the chemokine CCL2 (formerly called MCP-1). Because attenuated caveolin-1 levels have also been correlated with heightened permeability of other endothelia, the objective of this study was to test the hypothesis that reduced caveolin-1 expression is causally linked to the action of CCL2 on BMEC junctional protein expression and barrier integrity. This was achieved using adenovirus to nondestructively deliver caveolin-1 siRNA (Ad-siCav-1) to BMEC monolayers, which model the blood-brain barrier (BBB). Treatment with siRNA reduced the caveolin-1 protein level as well as occludin and ZO-1. Additionally, occludin exhibited dissociation from the cytoskeletal framework. These changes were attended by comparable alterations in adherens junction (AJ)–associated proteins, VE-cadherin and β-catenin, increased BMEC paracellular permeability, and facilitated the ability of CCL2 to stimulate monocytic transendothelial migration. Furthermore, treating BMECs with cavtratin, a synthetic cell-permeable peptide encoding the caveolin-1 scaffolding domain, antagonized effects of both Ad-siCav-1 and CCL2. These results collectively highlight caveolin-1 loss as a critical step in CCL2-induced modulation of BMEC junctional protein expression and integrity, and possibly serve a crucial role in regulating inflammation at the BBB.", "publicationTitle": "Blood", "publisher": "", "place": "", "date": "02/15/2007", "volume": "109", "issue": "4", "section": "", "partNumber": "", "partTitle": "", "pages": "1515-1523", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Blood", "DOI": "10.1182/blood-2006-07-034009", "citationKey": "", "url": "http://bloodjournal.hematologylibrary.org/content/109/4/1515", "accessDate": "2013-05-07T02:31:22Z", "PMID": "", "PMCID": "", "ISSN": "0006-4971, 1528-0020", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "en", "libraryCatalog": "bloodjournal.hematologylibrary.org", "callNumber": "", "rights": "", "extra": "PMID: 17023578", "tags": [], "collections": [ "J3P8Q9HT" ], "relations": {}, "dateAdded": "2013-05-07T02:31:22Z", "dateModified": "2013-05-07T02:31:22Z" } }, { "key": "8P4RGKPP", "version": 16, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/8P4RGKPP", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/8P4RGKPP", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/5Z65K9W6", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } } }, "data": { "key": "8P4RGKPP", "version": 16, "parentItem": "5Z65K9W6", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed entry", "accessDate": "2013-05-07T02:31:22Z", "url": "http://www.ncbi.nlm.nih.gov/pubmed/17023578", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-05-07T02:31:22Z", "dateModified": "2013-05-07T02:31:22Z" } }, { "key": "MH922ZW5", "version": 12, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/MH922ZW5", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/MH922ZW5", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/8WKV7SDV", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } } }, "data": { "key": "MH922ZW5", "version": 12, "parentItem": "8WKV7SDV", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed entry", "accessDate": "2013-05-07T02:18:31Z", "url": "http://www.ncbi.nlm.nih.gov/pubmed/17021377", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-05-07T02:18:31Z", "dateModified": "2013-05-07T02:18:31Z" } }, { "key": "8WKV7SDV", "version": 12, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/8WKV7SDV", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/8WKV7SDV", "type": "text/html" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "creatorSummary": "Enriori et al.", "parsedDate": "2006-08", "numChildren": 1 }, "data": { "key": "8WKV7SDV", "version": 12, "itemType": "journalArticle", "title": "Leptin resistance and obesity", "creators": [ { "creatorType": "author", "firstName": "Pablo J", "lastName": "Enriori" }, { "creatorType": "author", "firstName": "Anne E", "lastName": "Evans" }, { "creatorType": "author", "firstName": "Puspha", "lastName": "Sinnayah" }, { "creatorType": "author", "firstName": "Michael A", "lastName": "Cowley" } ], "abstractNote": "The prevalence of obesity, and the human and economic costs of the disease, creates a need for better therapeutics and better understanding of the physiological processes that balance energy intake and energy expenditure. Leptin is the primary signal from energy stores and exerts negative feedback effects on energy intake. In common obesity, leptin loses the ability to inhibit energy intake and increase energy expenditure; this is termed leptin resistance. This review discusses the evidence in support of leptin resistance in mouse models and humans and the possible mechanisms of leptin resistance.", "publicationTitle": "Obesity (Silver Spring, Md.)", "publisher": "", "place": "", "date": "Aug 2006", "volume": "14 Suppl 5", "issue": "", "section": "", "partNumber": "", "partTitle": "", "pages": "254S-258S", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Obesity (Silver Spring)", "DOI": "10.1038/oby.2006.319", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "1930-7381", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 17021377", "tags": [ { "tag": "Adipose Tissue", "type": 1 }, { "tag": "Animals", "type": 1 }, { "tag": "Energy Intake", "type": 1 }, { "tag": "Energy Metabolism", "type": 1 }, { "tag": "Humans", "type": 1 }, { "tag": "Leptin", "type": 1 }, { "tag": "Mice", "type": 1 }, { "tag": "Obesity", "type": 1 }, { "tag": "Signal Transduction", "type": 1 } ], "collections": [ "J3P8Q9HT" ], "relations": {}, "dateAdded": "2013-05-07T02:18:31Z", "dateModified": "2013-05-07T02:18:31Z" } }, { "key": "956RZMJT", "version": 11, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/956RZMJT", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/956RZMJT", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/JVDTRBAU", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } } }, "data": { "key": "956RZMJT", "version": 11, "parentItem": "JVDTRBAU", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed entry", "accessDate": "2013-05-06T23:23:20Z", "url": "http://www.ncbi.nlm.nih.gov/pubmed/11739396", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-05-06T23:23:20Z", "dateModified": "2013-05-06T23:23:20Z" } }, { "key": "JVDTRBAU", "version": 11, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/JVDTRBAU", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/JVDTRBAU", "type": "text/html" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "creatorSummary": "Razani et al.", "parsedDate": "2002-03-08", "numChildren": 1 }, "data": { "key": "JVDTRBAU", "version": 11, "itemType": "journalArticle", "title": "Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities", "creators": [ { "creatorType": "author", "firstName": "Babak", "lastName": "Razani" }, { "creatorType": "author", "firstName": "Terry P", "lastName": "Combs" }, { "creatorType": "author", "firstName": "Xiao Bo", "lastName": "Wang" }, { "creatorType": "author", "firstName": "Philippe G", "lastName": "Frank" }, { "creatorType": "author", "firstName": "David S", "lastName": "Park" }, { "creatorType": "author", "firstName": "Robert G", "lastName": "Russell" }, { "creatorType": "author", "firstName": "Maomi", "lastName": "Li" }, { "creatorType": "author", "firstName": "Baiyu", "lastName": "Tang" }, { "creatorType": "author", "firstName": "Linda A", "lastName": "Jelicks" }, { "creatorType": "author", "firstName": "Philipp E", "lastName": "Scherer" }, { "creatorType": "author", "firstName": "Michael P", "lastName": "Lisanti" } ], "abstractNote": "Caveolae organelles and caveolin-1 protein expression are most abundant in adipocytes and endothelial cells. Our initial report on mice lacking caveolin-1 (Cav-1) demonstrated a loss of caveolae and perturbations in endothelial cell function. More recently, however, observation of the Cav-1-deficient cohorts into old age revealed significantly lower body weights, as compared with wild-type controls. These results suggest that Cav-1 null mice may have problems with lipid metabolism and/or adipocyte functioning. To test this hypothesis directly, we placed a cohort of wild-type and Cav-1 null mice on a high fat diet. Interestingly, despite being hyperphagic, Cav-1 null mice show overt resistance to diet-induced obesity. As predicted, adipocytes from Cav-1 null null mice lack caveolae membranes. Early on, a lack of caveolin-1 selectively affects only the female mammary gland fat pad and results in a near complete ablation of the hypo-dermal fat layer. There are also indications of generalized adipose tissue pathology. With increasing age, a systemic decompensation in lipid accumulation occurs resulting in dramatically smaller fat pads, histologically reduced adipocyte cell diameter, and a poorly differentiated/hypercellular white adipose parenchyma. To gain mechanistic insights into this phenotype, we show that, although serum insulin, glucose, and cholesterol levels are entirely normal, Cav-1 null mice have severely elevated triglyceride and free fatty acid levels, especially in the post-prandial state. However, this build-up of triglyceride-rich chylomicrons/very low density lipoproteins is not due to perturbed lipoprotein lipase activity, a major culprit of isolated hypertriglyceridemia. The lean body phenotype and metabolic defects observed in Cav-1 null mice are consistent with the previously proposed functions of caveolin-1 and caveolae in adipocytes. Our results show for the first time a clear role for caveolins in systemic lipid homeostasis in vivo and place caveolin-1/caveolae as major factors in hyperlipidemias and obesity.", "publicationTitle": "The Journal of biological chemistry", "publisher": "", "place": "", "date": "Mar 8, 2002", "volume": "277", "issue": "10", "section": "", "partNumber": "", "partTitle": "", "pages": "8635-8647", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J. Biol. Chem.", "DOI": "10.1074/jbc.M110970200", "citationKey": "", "url": "", "accessDate": "", "PMID": "", "PMCID": "", "ISSN": "0021-9258", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "eng", "libraryCatalog": "NCBI PubMed", "callNumber": "", "rights": "", "extra": "PMID: 11739396", "tags": [ { "tag": "Adipocytes", "type": 1 }, { "tag": "Adipose Tissue", "type": 1 }, { "tag": "Animals", "type": 1 }, { "tag": "Body Weight", "type": 1 }, { "tag": "Caveolin 1", "type": 1 }, { "tag": "Caveolins", "type": 1 }, { "tag": "Diet", "type": 1 }, { "tag": "Electrophoresis, Polyacrylamide Gel", "type": 1 }, { "tag": "Feeding Behavior", "type": 1 }, { "tag": "Female", "type": 1 }, { "tag": "Homeostasis", "type": 1 }, { "tag": "Hypertriglyceridemia", "type": 1 }, { "tag": "Immunoblotting", "type": 1 }, { "tag": "Kinetics", "type": 1 }, { "tag": "Lipase", "type": 1 }, { "tag": "Lipid Metabolism", "type": 1 }, { "tag": "Magnetic Resonance Imaging", "type": 1 }, { "tag": "Male", "type": 1 }, { "tag": "Mice", "type": 1 }, { "tag": "Mice, Inbred C57BL", "type": 1 }, { "tag": "Mice, Transgenic", "type": 1 }, { "tag": "Microscopy, Electron", "type": 1 }, { "tag": "Obesity", "type": 1 }, { "tag": "Phenotype", "type": 1 }, { "tag": "Sex Factors", "type": 1 }, { "tag": "Time Factors", "type": 1 } ], "collections": [ "J3P8Q9HT" ], "relations": {}, "dateAdded": "2013-05-06T23:23:20Z", "dateModified": "2013-05-06T23:23:20Z" } }, { "key": "IXFWPCJ3", "version": 11, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/IXFWPCJ3", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/IXFWPCJ3", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/TJTW2MDK", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "IXFWPCJ3", "version": 11, "parentItem": "TJTW2MDK", "itemType": "attachment", "linkMode": "imported_url", "title": "Full Text PDF", "accessDate": "2013-05-06T23:22:41Z", "url": "http://www.reproduction-online.org/content/140/2/223.full.pdf", "note": "", "contentType": "application/pdf", "charset": "", "filename": "Hölzenspies et al. - 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J.", "lastName": "Roelen" }, { "creatorType": "author", "firstName": "Ben", "lastName": "Colenbrander" }, { "creatorType": "author", "firstName": "Roland A. P.", "lastName": "Romijn" }, { "creatorType": "author", "firstName": "Wieger", "lastName": "Hemrika" }, { "creatorType": "author", "firstName": "Willem", "lastName": "Stoorvogel" }, { "creatorType": "author", "firstName": "Theo van", "lastName": "Haeften" } ], "abstractNote": "", "publicationTitle": "Reproduction", "publisher": "", "place": "", "date": "08/01/2010", "volume": "140", "issue": "2", "section": "", "partNumber": "", "partTitle": "", "pages": "223-233", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Reproduction", "DOI": "10.1530/REP-10-0045", "citationKey": "", "url": "http://www.reproduction-online.org/content/140/2/223", "accessDate": "2013-05-06T23:22:41Z", "PMID": "", "PMCID": "", "ISSN": "1470-1626, 1741-7899", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "en", "libraryCatalog": "www.reproduction-online.org", "callNumber": "", "rights": "", "extra": "PMID: 20522479", "tags": [], "collections": [ "J3P8Q9HT" ], "relations": {}, "dateAdded": "2013-05-06T23:22:41Z", "dateModified": "2013-05-06T23:22:41Z" } }, { "key": "75D6ANB6", "version": 11, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/75D6ANB6", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/75D6ANB6", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/58X2MPXJ", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "75D6ANB6", "version": 11, "parentItem": "58X2MPXJ", "itemType": "attachment", "linkMode": "imported_url", "title": "PubMed Central Full Text PDF", "accessDate": "2013-05-06T23:21:46Z", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC507761/pdf/990014.pdf", "note": "", "contentType": "application/pdf", "charset": "", "filename": "Golden et al. - 1997 - Human blood-brain barrier leptin receptor. Binding.pdf", "md5": "739a850b48c4bdf8ddd3031fb398e381", "mtime": 1367882510431, "tags": [], "relations": {}, "dateAdded": "2013-05-06T23:21:46Z", "dateModified": "2013-05-06T23:21:50Z" } }, { "key": "CN67HV39", "version": 9, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/CN67HV39", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/CN67HV39", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/58X2MPXJ", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } } }, "data": { "key": "CN67HV39", "version": 9, "parentItem": "58X2MPXJ", "itemType": "attachment", "linkMode": "linked_url", "title": "PubMed Central Link", "accessDate": "2013-05-06T23:21:46Z", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC507761/", "note": "", "contentType": "text/html", "charset": "", "tags": [], "relations": {}, "dateAdded": "2013-05-06T23:21:46Z", "dateModified": "2013-05-06T23:21:46Z" } }, { "key": "58X2MPXJ", "version": 9, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/58X2MPXJ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/58X2MPXJ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "creatorSummary": "Golden et al.", "parsedDate": "1997-01-01", "numChildren": 2 }, "data": { "key": "58X2MPXJ", "version": 9, "itemType": "journalArticle", "title": "Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels.", "creators": [ { "creatorType": "author", "firstName": "P L", "lastName": "Golden" }, { "creatorType": "author", "firstName": "T J", "lastName": "Maccagnan" }, { "creatorType": "author", "firstName": "W M", "lastName": "Pardridge" } ], "abstractNote": "The peripheral production of leptin by adipose tissue and its putative effect as a signal of satiety in the central nervous system suggest that leptin gains access to the regions of the brain regulating energy balance by crossing the brain capillary endothelium, which constitutes the blood-brain barrier in vivo. The present experiments characterize the binding and internalization of mouse recombinant leptin in isolated human brain capillaries, an in vitro model of the human blood-brain barrier. Incubation of 125I-leptin with isolated human brain capillaries resulted in temperature-dependent binding: at 37 degrees C, approximately 65% of radiolabeled leptin was bound per milligram of capillary protein. Two-thirds of the bound radioactivity was resistant to removal by acid wash, demonstrating endocytosis of 125I-leptin into capillary cells. At 4 degrees C, binding to isolated capillaries was reduced to approximately 23%/mg of protein, the majority of which was acid wash resistant. Binding of 125I-leptin to brain capillary endothelial plasma membranes was saturable, described by a two-site binding model with a high-affinity dissociation constant of 5.1+/-2.8 nM and maximal binding capacity of 0.34+/-0.16 pmol/mg of membrane protein. Addition of porcine insulin or insulin-like growth factor at a final concentration of 100 nM had a negligible effect on leptin binding. These results provide evidence for a leptin receptor that mediates saturable, specific, temperature-dependent binding and endocytosis of leptin at the human blood-brain barrier.", "publicationTitle": "Journal of Clinical Investigation", "publisher": "", "place": "", "date": "1997-1-1", "volume": "99", "issue": "1", "section": "", "partNumber": "", "partTitle": "", "pages": "14-18", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "J Clin Invest", "DOI": "", "citationKey": "", "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC507761/", "accessDate": "2013-05-06T23:21:46Z", "PMID": "", "PMCID": "", "ISSN": "0021-9738", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "", "libraryCatalog": "PubMed Central", "callNumber": "", "rights": "", "extra": "PMID: 9011568\nPMCID: PMC507761", "tags": [], "collections": [ "J3P8Q9HT" ], "relations": {}, "dateAdded": "2013-05-06T23:21:46Z", "dateModified": "2013-05-06T23:21:46Z" } }, { "key": "3EZ64BMR", "version": 9, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/3EZ64BMR", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/3EZ64BMR", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/29EDZTHJ", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "numChildren": 0 }, "data": { "key": "3EZ64BMR", "version": 9, "parentItem": "29EDZTHJ", "itemType": "attachment", "linkMode": "imported_url", "title": "Full Text PDF", "accessDate": "2013-05-06T23:20:26Z", "url": "http://diabetes.diabetesjournals.org/content/53/5/1261.full.pdf", "note": "", "contentType": "application/pdf", "charset": "", "filename": "Cohen et al. - 2004 - Role of Caveolin-1 in the Modulation of Lipolysis .pdf", "md5": "7cd94e5f347b8c7bfde86ec0707480ac", "mtime": 1367882431378, "tags": [], "relations": {}, "dateAdded": "2013-05-06T23:20:26Z", "dateModified": "2013-05-06T23:20:31Z" } }, { "key": "KQZCRW3U", "version": 9, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/KQZCRW3U", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/KQZCRW3U", "type": "text/html" }, "up": { "href": "https://api.zotero.org/groups/130587/items/29EDZTHJ", "type": "application/json" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } } }, "data": { "key": "KQZCRW3U", "version": 9, "parentItem": "29EDZTHJ", "itemType": "attachment", "linkMode": "imported_url", "title": "Snapshot", "accessDate": "2013-05-06T23:20:26Z", "url": "http://diabetes.diabetesjournals.org/content/53/5/1261.full", "note": "", "contentType": "text/html", "charset": "utf-8", "filename": "1261.html", "md5": "f828347bf2e62b13945ba43a528e0e26", "mtime": 1367882427059, "tags": [], "relations": {}, "dateAdded": "2013-05-06T23:20:26Z", "dateModified": "2013-05-06T23:20:26Z" } }, { "key": "29EDZTHJ", "version": 8, "library": { "type": "group", "id": 130587, "name": "Capstone Thesis -LT", "links": { "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt", "type": "text/html" } } }, "links": { "self": { "href": "https://api.zotero.org/groups/130587/items/29EDZTHJ", "type": "application/json" }, "alternate": { "href": "https://www.zotero.org/groups/capstone_thesis_-lt/items/29EDZTHJ", "type": "text/html" } }, "meta": { "createdByUser": { "id": 503564, "username": "tc3tb", "name": "", "links": { "alternate": { "href": "https://www.zotero.org/tc3tb", "type": "text/html" } } }, "creatorSummary": "Cohen et al.", "parsedDate": "2004-05-01", "numChildren": 3 }, "data": { "key": "29EDZTHJ", "version": 8, "itemType": "journalArticle", "title": "Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation", "creators": [ { "creatorType": "author", "firstName": "Alex W.", "lastName": "Cohen" }, { "creatorType": "author", "firstName": "Babak", "lastName": "Razani" }, { "creatorType": "author", "firstName": "William", "lastName": "Schubert" }, { "creatorType": "author", "firstName": "Terence M.", "lastName": "Williams" }, { "creatorType": "author", "firstName": "Xiao Bo", "lastName": "Wang" }, { "creatorType": "author", "firstName": "Puneeth", "lastName": "Iyengar" }, { "creatorType": "author", "firstName": "Dawn L.", "lastName": "Brasaemle" }, { "creatorType": "author", "firstName": "Philipp E.", "lastName": "Scherer" }, { "creatorType": "author", "firstName": "Michael P.", "lastName": "Lisanti" } ], "abstractNote": "Recently, it was shown that caveolin-1 can be redirected from the cell surface to intracellular lipid droplets in a variety of cell types. Here, we directly address the role of caveolin-1 in lipid droplet formation and breakdown, showing that caveolin-1 null mice exhibit markedly attenuated lipolytic activity. Mechanistically, although the activity of protein kinase A (PKA) was greatly increased in caveolin-1 null adipocytes, the phosphorylation of perilipin was dramatically reduced, indicating that caveolin-1 may facilitate the PKA-mediated phosphorylation of perilipin. In support of this hypothesis, coimmunoprecipitation experiments revealed that treatment with a β3-adrenergic receptor agonist resulted in ligand-induced complex formation between perilipin, caveolin-1, and the catalytic subunit of PKA in wild-type but not in caveolin-1 null fat pads. We also show that caveolin-1 expression is important for efficient lipid droplet formation because caveolin-1 null embryonic fibroblasts stably transfected with perilipin accumulated ∼4.5-fold less lipid than perilipin-transfected wild-type cells. Finally, high-pressure freeze-substitution electron microscopy of adipose tissue revealed dramatic perturbations in the architecture of the “lipid droplet cortex” (the interface between the lipid droplet surface and the cytoplasm) in caveolin-1 null perigonadal adipocytes. Taken together, our data provide the first molecular genetic evidence that caveolin-1 plays a critical functional and structural role in the modulation of both lipid droplet biogenesis and metabolism in vivo.", "publicationTitle": "Diabetes", "publisher": "", "place": "", "date": "05/01/2004", "volume": "53", "issue": "5", "section": "", "partNumber": "", "partTitle": "", "pages": "1261-1270", "series": "", "seriesTitle": "", "seriesText": "", "journalAbbreviation": "Diabetes", "DOI": "10.2337/diabetes.53.5.1261", "citationKey": "", "url": "http://diabetes.diabetesjournals.org/content/53/5/1261", "accessDate": "2013-05-06T23:20:26Z", "PMID": "", "PMCID": "", "ISSN": "0012-1797, 1939-327X", "archive": "", "archiveLocation": "", "shortTitle": "", "language": "en", "libraryCatalog": "diabetes.diabetesjournals.org", "callNumber": "", "rights": "", "extra": "PMID: 15111495", "tags": [ { "tag": "CREB, cAMP response element binding", "type": 1 }, { "tag": "ER, endoplasmic reticulum", "type": 1 }, { "tag": "HSL, hormone-sensitive lipase", "type": 1 }, { "tag": "MEF, mouse embryonic fibroblast", "type": 1 }, { "tag": "NEFA, nonesterified fatty acid", "type": 1 }, { "tag": "PKA, protein kinase A", "type": 1 }, { "tag": "Peri-MEF, MEF transfected with the cDNA encoding perilipin A", "type": 1 }, { "tag": "RIPA, radioimmunoprecipitation assay", "type": 1 }, { "tag": "eNOS, endothelial nitric oxide synthase", "type": 1 }, { "tag": "mAb, monoclonal antibody", "type": 1 }, { "tag": "pAb, polyclonal antibody", "type": 1 } ], "collections": [ "J3P8Q9HT" ], "relations": {}, "dateAdded": "2013-05-06T23:20:26Z", "dateModified": "2013-05-06T23:20:26Z" } } ]