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<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="dw7MZPwE7H3DEuDLccYMMdqLZeAR3vUtujRRCFZ0HiQ7yVJBPvBOglWpxii3W6sN">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="dw7MZPwE7H3DEuDLccYMMdqLZeAR3vUtujRRCFZ0HiQ7yVJBPvBOglWpxii3W6sN">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="dw7MZPwE7H3DEuDLccYMMdqLZeAR3vUtujRRCFZ0HiQ7yVJBPvBOglWpxii3W6sN">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="dw7MZPwE7H3DEuDLccYMMdqLZeAR3vUtujRRCFZ0HiQ7yVJBPvBOglWpxii3W6sN">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="dw7MZPwE7H3DEuDLccYMMdqLZeAR3vUtujRRCFZ0HiQ7yVJBPvBOglWpxii3W6sN">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="17403372">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://linkinghub.elsevier.com/retrieve/pii/S1550-4131(07)00034-4"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=17403372&amp;db=pubmed&amp;nlmid=101233170"
title="See full text options at Elsevier Science"
data-ga-category="full_text"
data-ga-action="Elsevier Science"
data-ga-label="17403372"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="Elsevier Science full text link"><span class="text">
Elsevier Science
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/17403372/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=17403372&amp;db=pubmed&amp;nlmid=101233170"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="17403372"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/17403372/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/17403372/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="17403372" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F17403372%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="dw7MZPwE7H3DEuDLccYMMdqLZeAR3vUtujRRCFZ0HiQ7yVJBPvBOglWpxii3W6sN"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
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><sup class="key">1</sup> Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, and Children&#x27;s Hospital Oakland Research Institute 94609, USA. abeigneux@mednet.ucla.edu</li>
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<p>
The triglycerides in chylomicrons are hydrolyzed by lipoprotein lipase (LpL) along the luminal surface of the capillaries. However, the endothelial cell molecule that facilitates chylomicron processing by LpL has not yet been defined. Here, we show that glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a critical role in the lipolytic processing of chylomicrons. Gpihbp1-deficient mice exhibit a striking accumulation of chylomicrons in the plasma, even on a low-fat diet, resulting in milky plasma and plasma triglyceride levels as high as 5000 mg/dl. Normally, Gpihbp1 is expressed highly in heart and adipose tissue, the same tissues that express high levels of LpL. In these tissues, GPIHBP1 is located on the luminal face of the capillary endothelium. Expression of GPIHBP1 in cultured cells confers the ability to bind both LpL and chylomicrons. These studies strongly suggest that GPIHBP1 is an important platform for the LpL-mediated processing of chylomicrons in capillaries.
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data-image-height="363"
data-image-alt="Figure 1"
data-pmc-id="PMC1913910"
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b726/1913910/bf248c406a87/nihms-21131-f0001.gif"
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<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="504">
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<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><p> Generation of <i> Gpihbp1 </i> knockout mice.… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><p> Generation of <i> Gpihbp1 </i> knockout mice. (A) Sequence-replacement gene-targeting strategy for inactivating <i> Gpihbp1 </i> .… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1
</strong>
<div class="figure-caption-contents">Generation of <i>Gpihbp1</i> knockout mice. (A) Sequence-replacement gene-targeting strategy for inactivating <i>Gpihbp1</i>. Locations of the 5 and 3 probes (bars) for Southern blot analysis and PCR primers (arrows) for genotyping are shown. An ethidium-bromide stained agarose gel illustrates a PCR strategy for genotyping <i>Gpihbp1</i>+/+, <i>Gpihbp1</i>+/, and <i>Gpihbp1</i>/ mice. A description of the PCR genotyping strategy is contained in the <i>Experimental Procedures</i>. (B) A northern blot, probed with a <i>Gpihbp1</i> cDNA probe spanning the complete open reading frame of <i>Gpihbp1</i>, shows the absence of <i>Gpihbp1</i> expression in heart and brown adipose tissue (BAT) from <i>Gpihbp1</i>/ mice. (C) Western blot with a GPIHBP1-specific rabbit antiserum showing GPIHBP1 in brown adipose tissue (BAT) and gonadal fat pad extracts from <i>Gpihbp1</i>+/+ mice but not<i> Gpihbp1</i>/ mice. As a control, extracts from HeLa cells that had been transfected with an untagged or an S-proteintagged GPIHBP1 construct were included.</div>
</figcaption>
</figure>
<figure class="figure-item "
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data-slide-index="1"
data-label-slug="figure-2">
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itemprop="contentUrl"
aria-describedby="figure-caption-1"
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data-image-width="504"
data-image-height="585"
data-image-alt="Figure 2"
data-pmc-id="PMC1913910"
data-figure-id="F2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b726/1913910/b41ac092d9e0/nihms-21131-f0002.gif"
alt="Figure 2" />
</a>
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
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<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Analysis of <i> Gpihbp1 </i> knockout mice.… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> Analysis of <i> Gpihbp1 </i> knockout mice. (A) Photograph of blood samples from three two-month-old… </p></div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2
</strong>
<div class="figure-caption-contents">Analysis of <i>Gpihbp1</i> knockout mice. (A) Photograph of blood samples from three two-month-old littermate chow-fed male mice (after low-speed centrifugation to sediment blood cells), revealing “milky” plasma in <i>Gpihbp1</i>/ mice. (B) Plasma triglyceride levels in <i>Gpihbp1</i>+/+, <i>Gpihbp1</i>+/, and <i>Gpihbp1</i>/ mice at different ages, showing higher triglyceride levels in <i>Gpihbp1</i>/ mice (<i>P</i> &lt; 0.0001 in each age group). Triglyceride levels in <i>Gpihbp1</i>+/+ and <i>Gpihbp1</i>+/ mice were not different. (C) Coomassie bluestained SDS-polyacrylamide gel of the <i>d</i> &lt; 1.006 g/ml lipoproteins of wild-type and <i>Gpihbp1</i>/ mice. (D) Western blot of mouse plasma (1.0 μl) with a mouse monoclonal antibody specific for apo-B48 and apo-B100 (Nguyen et al., 2006), showing increased amounts of apo-B48 in the plasma of <i>Gpihbp1</i>/ mice. (E) Distribution of triglycerides in the plasma lipoproteins of <i>Gpihbp1</i>+/+ and <i>Gpihbp1</i>/ mice. Plasma lipoproteins were separated by size on a Superose 6 FPLC column. Representative of two different experiments. (F) Distribution of lipoprotein sizes in the <i>d</i> &lt; 1.022 g/ml lipoproteins from <i>Gpihbp1</i>/ and <i>Gpihbp1</i>+/+ mice, as judged by dynamic laser light scattering methods. The median diameter of lipoproteins in <i>Gpihbp1</i>/ mice (<i>n</i> = 3) was 157% larger than in <i>Gpihbp1</i>+/+ mice (<i>n</i> = 6). Shown here are representative data from a single <i>Gpihbp1</i>/ and <i>Gpihbp1</i>+/+ mouse. Both <i>Gpihbp1</i>+/+ and <i>Gpihbp1</i>/ mice had bimodal distributions of lipoproteins; the larger subpopulation of particles in <i>Gpihbp1</i>/ mice, constituting 15.4% of the total particles, had diameters of 122289 nm; in <i>Gpihbp1</i>+/+ mice, the larger population of particles, constituting 2.9% of particles, were 94204 nm. The smaller subpopulation of particles in <i>Gpihbp1</i>/ and <i>Gpihbp1</i>+/+ mice had diameters of 39111 and 3386 nm, respectively. (G) Electron micrographs of negatively stained <i>d</i> &lt; 1.006 g/ml lipoproteins from the plasma of <i>Gpihbp1/</i> and <i>Gpihbp1+/+</i> mice, showing the larger lipoproteins in <i>Gpihbp1/</i> mice. Representative images from two <i>Gpihbp1/</i> and two <i>Gpihbp1+/+</i> samples. (H) Delayed clearance of retinyl esters in <i>Gpihbp1</i>/ mice. Retinyl palmitate (5,000 IU in 50 μl of vegetable oil) was administered to mice by gavage, and retinyl esters in the plasma were measured over the next 24 h. The inset shows the retinyl ester levels in <i>Gpihbp1</i>+/+ mice plotted on a smaller scale, showing that the levels in <i>Gpihbp1</i>+/+ mice peaked between 1 and 3 h and had largely disappeared by 10 h. Retinyl palmitate clearance studies were also performed in <i>Gpihbp1</i>+/ mice, and they were indistinguishable from those of <i>Gpihbp1</i>+/+ mice. The retinyl palmitate clearance studies were performed in 7 <i>Gpihbp1</i>/, 6 <i>Gpihbp1</i>+/, and 5 <i>Gpihbp1</i>+/+ mice. Shown here are representative curves for 3 <i>Gpihbp1</i>/ and <i>Gpihbp1</i>+/+ mice. When the retinyl ester measurements for all of the mice were analyzed, the differences between the <i>Gpihbp1</i>/ mice and the other two groups were statistically significant at each time point (<i>P</i> &lt; 0.001). There were no differences between <i>Gpihbp1</i>+/ and <i>Gpihbp1</i>+/+ mice.</div>
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itemprop="associatedMedia"
data-slide-index="2"
data-label-slug="figure-3">
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b726/1913910/72c5b9812ebd/nihms-21131-f0003.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="504"
data-image-height="600"
data-image-alt="Figure 3"
data-pmc-id="PMC1913910"
data-figure-id="F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b726/1913910/e6dc626459e0/nihms-21131-f0003.gif"
alt="Figure 3" />
</a>
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<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> GPIHBP1 is located within the… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> GPIHBP1 is located within the lumen of the capillary endothelium of brown adipose… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3
</strong>
<div class="figure-caption-contents">GPIHBP1 is located within the lumen of the capillary endothelium of brown adipose tissue and heart. (A) Epifluorescence microscopy showing the binding of a rat monoclonal antibody against mouse CD31 (red) and a rabbit antiserum against GPIHBP1 (green) to brown adipose tissue of <i>Gpihbp1</i>+/+ and <i>Gpihbp1</i>/ mice. Images were taken with a 40× objective. (B) Confocal microscopy images showing the binding of antibodies against CD31 and GPIHBP1 to brown adipose tissue from a <i>Gpihbp1</i>+/+ mouse. Images were taken with a 100× objective. The arrow indicates the location of a capillary (shown at higher magnification in the insert; 100× objective with 4× digital zoom). The high-magnification micrograph shows a cross-section of a capillary, revealing that GPIHBP1 staining is particularly prominent on the luminal side of the capillary. (C) Confocal microscopy images showing the binding of antibodies against CD31 and GPIHBP1 to heart tissue from a <i>Gpihbp1</i>+/+ mouse. GPIHBP1 staining is particularly prominent on the luminal face of the capillary endothelium. Images were taken with a 100× objective.</div>
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data-slide-index="3"
data-label-slug="figure-4">
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itemprop="contentUrl"
aria-describedby="figure-caption-3"
role="button"
data-image-width="480"
data-image-height="1080"
data-image-alt="Figure 4"
data-pmc-id="PMC1913910"
data-figure-id="F4">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b726/1913910/839bef7dfd29/nihms-21131-f0004.gif"
alt="Figure 4" />
</a>
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<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Separation of LpL and HL… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> Separation of LpL and HL in the post-heparin plasma of <i> Gpihbp1/ </i> and wild-type… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4
</strong>
<div class="figure-caption-contents">Separation of LpL and HL in the post-heparin plasma of <i>Gpihbp1/</i> and wild-type mice on a heparin-Sepharose column. (A) Lipase activities in the different fractions (representative data of four independent experiments). In these studies, the identities of the LpL and HL peaks were verified with immunoassays (B and C, respectively) (Cisar et al., 1989). The specific activity of the LpL in fractions 2125 of the wild-type and <i>Gpihbp1/</i> mouse plasma was not different. Each data point represents the average of duplicate analyses.</div>
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<p> Figure 5 </p>
</strong>
<div class="figure-caption-contents"><p> Generating cell lines expressing a… </p></div>
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<p> Figure 5 </p>
</strong>
<div class="figure-caption-contents"><p> Generating cell lines expressing a <i> Gpihbp1 </i> cDNA and testing the ability of GPIHBP1… </p></div>
</div>
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Figure 5
</strong>
<div class="figure-caption-contents">Generating cell lines expressing a <i>Gpihbp1</i> cDNA and testing the ability of GPIHBP1 to bind LpL. In preliminary studies, we showed that the expression of <i>Gpihbp1</i> was absent in wild-type CHO cells. (A) Confocal immunofluorescence microscopy showing the expression of an S-proteintagged GPIHBP1 on the surface of CHO ldlA7 cells. GPIHBP1 was visualized with a FITC-conjugated goat antibody against the S-protein tag (green) and DNA was visualized with DAPI (blue). (B) Western blot analysis of cell extracts and cell culture medium from HeLa cells that had been transfected with a mouse <i>Gpihbp1</i> cDNA, before and after treatment of the cells with PIPLC. (C) Binding of LpL to pgsA-745 CHO cells stably transfected with a cDNA encoding mouse <i>Gpihbp1</i> (pcDNA3-<i>Gpihbp1</i>, see Experimental Procedures) or empty vector. Cells were incubated for 2 h with increasing amounts of avian LpL. Following the incubation, the amount of bound LpL was measured with an ELISA. Each data point represents the mean of triplicates (± S.D.). Standard deviations are too small to be seen. (D) Binding of avian LpL (2.5 μg/ml) to pgsA-745 CHO cells transfected with pcDNA3-<i>Gpihbp1</i> or empty vector, before and after treatment with PIPLC. Each bar represents the mean (± S.D.) of triplicate determinations; in some cases, the standard deviations are too small to be seen. For several groups, the standard error bars are too small to be seen. In parallel experiments, pgsB-761 CHO cells transfected with the <i>Gpihbp1</i> cDNA also bound 10-fold more LpL than cells transfected with the empty vector. In wild-type CHO cells, LpL binding to nontransfected cells was greater (as a result of the expected binding of LpL to HSPGs), but we consistently observed a 70% increase in LpL binding to <i>Gpihbp1</i>-transfected cells. (E) Binding of avian LpL (2.5 μg/ml) to pgsA-745 CHO cells transfected with pcDNA3-<i>Gpihbp1</i> or empty vector, before and after treatment with heparin (1 U/ml). (F) Western blot analysis of cell extracts and cell culture medium from pgsA-745 CHO cells transfected with a mouse <i>Gpihbp1</i> cDNA (tagged and untagged) or empty vector, alone or in combination with a human <i>LPL</i> cDNA (with a C-terminus V5 tag), before and after treatment of the cells with heparin (1 U/ml).</div>
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<p> Figure 6 </p>
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<div class="figure-caption-contents"><p> Binding of chylomicrons to CHO-ldlA7… </p></div>
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<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><p> Binding of chylomicrons to CHO-ldlA7 cells expressing mouse GPIHBP1. (A) The binding of… </p></div>
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Figure 6
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<div class="figure-caption-contents">Binding of chylomicrons to CHO-ldlA7 cells expressing mouse GPIHBP1. (A) The binding of DiI-labeled chylomicrons (red) to nonpermeabilized CHO-ldlA7 cells that had been stably transfected with a mouse <i>Gpihbp1</i> cDNA (or empty vector) was measured at 4°C, before and after PIPLC treatment. GPIHBP1 expression was detected with the rabbit anti-GPIHBP1 antiserum and a FITC-labeled anti-rabbit IgG antibody (green). DNA was visualized with a DAPI stain (blue). (B) Binding of DiI-labeled chylomicrons (red) to CHO-ldlA7 cells that had been transiently transfected with a mouse <i>Gpihbp1</i> cDNA. GPIHBP1 expression was detected as described in Panel A.</div>
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<p> Figure 7 </p>
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<div class="figure-caption-contents"><p> Regulation of <i> Gpihbp1 </i> expression in… </p></div>
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<p> Figure 7 </p>
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<div class="figure-caption-contents"><p> Regulation of <i> Gpihbp1 </i> expression in quadriceps according to feeding status. RNA was isolated… </p></div>
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Figure 7
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<div class="figure-caption-contents">Regulation of <i>Gpihbp1</i> expression in quadriceps according to feeding status. RNA was isolated from fed mice, fasted mice (16 h), and fasted/re-fed mice (6 h post-refeeding a high-carbohydrate diet) (10-week-old wild-type C57BL/6 male mice; <i>n</i> = 10 per group), and the expression of <i>Gpihbp1</i> measured by quantitative RT-PCR (mean ± S.D.). β-2 microglobulin expression was used to normalize the data. Values show the amount of <i>Gpihbp1</i> mRNA relative to that in fed mice. ***, <i>P</i> &lt; 0.001.</div>
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Chylomicrons and lipoprotein lipase at the endothelial surface: bound and GAG-ged?
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Beckstead JA, Oda MN, Martin DDO, Forte TM, Bielicki JK, Berger T, Luty R, Kay CM, Ryan RO. Structure-Function Studies of Human Apolipoprotein A-V: A Regulator of Plasma Lipid Homeostasis. Biochemistry. 2003;42:94169423.
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Bengtsson G, Olivecrona T. Apolipoprotein CII enhances hydrolysis of monoglycerides by lipoprotein lipase, but the effect is abolished by fatty acids. FEBS Lett. 1979;106:345348.
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