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{{Short description|One of the five major groups of lipoprotein}}
{{More citations needed|date=December 2009}}
[[File:2512 Chylomicrons Contain Triglycerides Cholesterol Molecules and Other Lipids.jpg|Schematic image showing a chylomicron|right|thumb|300px]]
'''Chylomicrons''' (from the Greek χυλός, '''chylos''', meaning ''juice'' (of plants or animals), and '''micron''', meaning ''small''),<ref>{{Cite web |title=Definition of CHYLOMICRONS |url=https://www.merriam-webster.com/dictionary/chylomicrons |access-date=2024-04-26 |website=www.merriam-webster.com |language=en}}</ref> also known as '''ultra low-density lipoproteins''' ('''ULDL'''), are [[lipoprotein|lipoprotein particles]] that consist of [[triglyceride]]s (83–92%), [[phospholipid]]s (6–12%), [[cholesterol]] (1–3%), and [[protein]]s (1–2%). They transport dietary [[lipid]]s, such as [[fat]]s and cholesterol, from the [[intestines]] to other locations in the body, within the water-based solution of the [[bloodstream]].<ref>{{cite journal |last1=Gofman |first1=John W. |last2=Jones |first2=Hardin B. |last3=Lindgren |first3=Frank T. |last4=Lyon |first4=Thomas P. |last5=Elliott |first5=Harold A. |last6=Strisower |first6=Beverly |year=1950 |title=Blood Lipids and Human Atherosclerosis |url=http://circ.ahajournals.org/content/2/2/161.full.pdf |journal=Circulation |volume=2 |issue=2 |pages=161–178 |doi=10.1161/01.cir.2.2.161 |pmid=15427204 |s2cid=402420 |doi-access=free}}</ref> ULDLs are one of the five major groups lipoproteins are divided into based on their [[density]]. A protein specific to chylomicrons is [[Apolipoprotein B#Molecular biology|ApoB48]]{{Broken anchor|date=2025-05-25|bot=User:Cewbot/log/20201008/configuration|target_link=Apolipoprotein B#Molecular biology|reason= The anchor (Molecular biology) [[Special:Diff/1292194511|has been deleted]].|diff_id=1292194511}}.
There is an inverse relationship in the density and size of lipoprotein particles: fats have a lower density than water or smaller protein molecules, and the larger particles have a higher ratio of internal fat molecules with respect to the outer [[emulsifying]] protein molecules in the shell. ULDLs, if in the region of 1,000 nm or more, are the only lipoprotein particles that can be seen using a light microscope, at maximum magnification. All the other classes are submicroscopic.
== Function ==
{{Lipoproteins}}▼
[[Image:Chylomicron.svg|thumb|250px|'''Chylomicron structure'''<br />'''ApoA, ApoB, ApoC, ApoE''' ([[apolipoprotein]]s); '''T''' ([[triacylglycerol]]); '''C''' ([[cholesterol]]); green ([[phospholipid]]s)]]
Chylomicrons transport lipids absorbed from the intestine to [[adipose]], cardiac, and skeletal muscle tissue, where their triglyceride components are hydrolyzed by the activity of the [[lipoprotein lipase]], allowing the released [[free fatty acids]] to be absorbed by the tissues. When a large portion of the triglyceride core has been hydrolyzed, chylomicron remnants are formed and are taken up by the liver, thereby also transferring dietary fat to the liver.
[[Category:Lipoproteins]]▼
== Stages ==
=== Nascent chylomicrons ===
In the small intestine, dietary [[triglyceride]]s are emulsified by bile and digested by [[Pancreatic lipase family|pancreatic lipases]], resulting in the formation of [[monoglyceride]]s and [[fatty acid]]s. These lipids are absorbed into [[enterocyte]]s via [[Passive transport|passive diffusion]]. Inside these cells, monoglycerides and fatty acids are transported to the [[smooth endoplasmic reticulum]] (smooth ER), where they are re-esterified to form triglycerides.<ref>{{Cite journal |last1=Schwenk |first1=Robert W. |last2=Holloway |first2=Graham P. |last3=Luiken |first3=Joost J. F. P. |last4=Bonen |first4=Arend |last5=Glatz |first5=Jan F. C. |date=2010-04-01 |title=Fatty acid transport across the cell membrane: Regulation by fatty acid transporters |url=https://www.plefa.com/article/S0952-3278(10)00073-6/abstract |journal=Prostaglandins, Leukotrienes and Essential Fatty Acids |language=English |volume=82 |issue=4 |pages=149–154 |doi=10.1016/j.plefa.2010.02.029 |issn=0952-3278 |pmid=20206486}}</ref> These triglycerides, along with phospholipids and cholesterol, are added to [[apolipoprotein B]]48 to form nascent chylomicrons<ref>{{Citation |last=Kiani |first=Reza |title=Chapter 18 - Dyslipidemia |date=2018-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780323511490000183 |work=Practical Cardiology |pages=303–309 |editor-last=Maleki |editor-first=Majid |publisher=Elsevier |language=en |doi=10.1016/b978-0-323-51149-0.00018-3 |isbn=978-0-323-51149-0 |access-date=2022-12-06 |editor2-last=Alizadehasl |editor2-first=Azin |editor3-last=Haghjoo |editor3-first=Majid|url-access=subscription }}</ref> (also referred to as '''immature chylomicrons''' or '''pre-chylomicrons''').
After synthesis in the smooth ER, nascent chylomicrons are transported to the [[Golgi apparatus]] by [[SAR1B]] proteins.<ref>{{Cite web |title=SAR1B gene: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/gene/sar1b/ |access-date=2022-12-06 |website=medlineplus.gov |language=en}}</ref> The transport of nascent chylomicrons within the secretory pathway is facilitated by protein transport vesicles (PCTVs). PCTVs are uniquely equipped with [[SNARE protein|v-SNARE]] and [[Vesicle-associated membrane protein 7|VAMP-7]] proteins, which aid in their fusion with the cis-Golgi compartment. This transport is facilitated by [[COPII]] proteins, including Sec23/24, which select cargo and facilitate vesicle budding from the ER membrane.<ref>{{Cite journal |last1=Giammanco |first1=Antonina |last2=Cefalù |first2=Angelo B. |last3=Noto |first3=Davide |last4=Averna |first4=Maurizio R. |date=2015-03-20 |title=The pathophysiology of intestinal lipoprotein production |journal=Frontiers in Physiology |language=English |volume=6 |page=61 |doi=10.3389/fphys.2015.00061 |doi-access=free |issn=1664-042X |pmc=4367171 |pmid=25852563}}</ref>
During transit through the Golgi, nascent chylomicrons undergo enzymatic modification and lipidation processes, resulting in the formation of '''mature chylomicrons'''.
=== Mature chylomicrons ===
Mature chylomicrons are released through the [[basolateral membrane]] of [[enterocyte]]s (via the [[secretory pathway]]) into [[lacteal]]s,<ref>{{Citation |last1=Bodewes |first1=Frank A.J.A. |title=Persistent Fat Malabsorption in Cystic Fibrosis |date=2015 |work=Diet and Exercise in Cystic Fibrosis |pages=373–381 |url=https://doi.org/10.1016/B978-0-12-800051-9.00041-9 |access-date=2024-06-29 |publisher=Elsevier |doi=10.1016/b978-0-12-800051-9.00041-9 |isbn=978-0-12-800051-9 |last2=Wouthuyzen-Bakker |first2=Marjan |last3=Verkade |first3=Henkjan J.|url-access=subscription }}</ref> [[Lymph capillary|lymphatic capillaries]] in the [[Intestinal villus|villi]] of the [[small intestine]]. [[Lymph]] that contains chylomicrons (and other emulsified fats) is referred to as [[chyle]]. The [[lymphatic vessel|lymphatic circulation]] carries chyle to the [[lymphatic ducts]] before it enters the [[venous return]] of the systemic [[circulatory system|circulation]] via [[subclavian vein]]s. From here, chylomicrons can supply tissue throughout the body with fat absorbed from the diet.<ref>{{cite book|last1=Smith|first1=Sareen S. Gropper, Jack L.|last2=Smith|first2=Jack S.|title=Advanced nutrition and human metabolism|date=2013|publisher=Wadsworth/Cengage Learning|___location=Belmont, CA|isbn=978-1133104056|edition=6th}}</ref> Because they enter the bloodstream in this way, digested lipids (in the form of chylomicrons) bypass the [[hepatic portal system]] and thus avoid [[first pass metabolism]], unlike digested [[carbohydrate]]s (in the form of [[monosaccharide]]s) and [[protein]]s (in the form of [[amino acid]]s).
While circulating in blood, [[high-density lipoprotein]]s (HDLs) donate essential components including [[apolipoprotein C-II]] (APOC2) and [[apolipoprotein E]] (APOE) to the mature chylomicron. APOC2 is a crucial coenzyme for the activity of [[lipoprotein lipase]] (LPL), which hydrolyzes triglycerides within chylomicrons.
===Chylomicron remnants===
Once triglyceride stores are distributed, chylomicrons return APOC2 to [[High-density lipoprotein|HDLs]] while retaining APOE, transforming into a chylomicron remnant. ApoB48 and APOE are important to identify the chylomicron remnant in the liver for endocytosis and breakdown.
== Pathology ==
=== Hyperchylomicronemia ===
Hyperchylomicronemia is characterized by an excessive presence of chylomicrons in the blood, leading to extreme [[hypertriglyceridemia]]. Clinical manifestations of this disorder include [[Xanthoma#Eruptive xanthoma|eruptive xanthomas]], [[lipaemia retinalis]], [[hepatosplenomegaly]], recurrent [[abdominal pain]], and [[acute pancreatitis]]. This condition can be caused by genetic mutations (see below) or secondary factors such as [[Diabetes|uncontrolled diabetes]] or [[Alcoholism|alcohol use disorder]].<ref name=":0">{{Cite journal |last1=Julve |first1=Josep |last2=Martín-Campos |first2=Jesús M. |last3=Escolà-Gil |first3=Joan Carles |last4=Blanco-Vaca |first4=Francisco |year=2016 |title=Chylomicrons: Advances in biology, pathology, laboratory testing, and therapeutics |url=https://www.researchgate.net/publication/293638020 |journal=Clinica Chimica Acta |volume=455 |pages=134–148 |doi=10.1016/j.cca.2016.02.004 |pmid=26868089}}</ref>
=== Hypochylomicronemia ===
Hypochylomicronemia refers to abnormally low levels or complete absence of chylomicrons in the blood, particularly after a meal (postprandial). This condition can result from genetic mutations (see below), as well as certain malabsorption syndromes or deficiencies in dietary fat intake.<ref name=":0" />
== Related disorders ==
=== Chylomicron remnants and cardiovascular disease ===
Chylomicron remnants are the lipoprotein particles left after chylomicrons have delivered triglycerides to tissues. Elevated levels of these remnants contribute to [[hyperlipidemia]], which is considered an important risk factor for [[cardiovascular disease]].<ref name=":0" />
Recent studies have demonstrated that chylomicron remnants can penetrate the [[tunica intima]] and become trapped in the subendothelial space. This process enhances the deposition of cholesterol in the arterial wall, which is a critical step in the formation of [[Atherosclerosis|atherosclerotic plaques]]. The retention and modification of these remnants within the arterial wall trigger [[Inflammation|inflammatory responses]], further accelerating the development of [[atherosclerosis]].<ref>{{Cite journal |last1=Tomkin |first1=Gerald H. |last2=Owens |first2=Daphne |date=2012 |title=The Chylomicron: Relationship to Atherosclerosis |journal=International Journal of Vascular Medicine |language=en |volume=2012 |pages=1–13 |doi=10.1155/2012/784536 |doi-access=free |issn=2090-2824 |pmc=3189596 |pmid=22007304}}</ref>
=== Related genetic disorders ===
==== Abetalipoproteinemia (ABL) ====
'''[[Abetalipoproteinemia]]''' (ABL; OMIM 200100) is a rare ''autosomal recessive'' disorder caused by mutations in both alleles of the [[Microsomal triglyceride transfer protein|MTP gene]]. This genetic defect leads to nearly undetectable levels of ApoB and very low plasma cholesterol levels. Patients with ABL exhibit fat malabsorption, [[steatorrhea]], and fat accumulation in enterocytes and hepatocytes. The condition also results in multiple vitamin deficiencies (E, A, K, and D) due to impaired lipoprotein assembly and transport. If untreated, ABL can cause neurological disturbances such as spinal-cerebellar degeneration, [[Peripheral neuropathy|peripheral neuropathies]], and [[retinitis pigmentosa]]. Early supplementation of fat-soluble vitamins can prevent these complications.<ref name=":1">{{Cite journal |last1=Giammanco |first1=Antonina |last2=Cefalù |first2=Angelo B. |last3=Noto |first3=Davide |last4=Averna |first4=Maurizio R. |date=2015-03-20 |title=The pathophysiology of intestinal lipoprotein production |journal=Frontiers in Physiology |language=English |volume=6 |page=61 |doi=10.3389/fphys.2015.00061 |doi-access=free |issn=1664-042X |pmc=4367171 |pmid=25852563}}</ref>
==== Homozygous hypobetalipoproteinemia (Ho-HBL) ====
'''[[Homozygous hypobetalipoproteinemia]]''' (Ho-HBL; OMIM 107730) is an extremely rare inherited disorder characterized by improper packaging and secretion of apoB-containing lipoproteins due to mutations in both alleles of the [[Apolipoprotein B|APOB gene]]. These mutations lead to apoB truncations or amino acid substitutions, resulting in the formation of short, abnormal apoBs that are unable to bind lipids and form chylomicrons. Clinical manifestations vary, ranging from lack of symptoms to features overlapping with those of ABL, including fat malabsorption and vitamin deficiencies.<ref name=":1" />
==== Chylomicron retention disease (CMRD) ====
'''[[Chylomicron retention disease]]''' (CMRD; OMIM #607689) is a rare ''autosomal recessive'' disorder caused by mutations in the [[SAR1B (gene)|SAR1B gene]]. Patients with CMRD present with chronic diarrhea, failure to thrive, hypocholesterolemia, and low levels of fat-soluble vitamins. The enterocytes of these patients fail to secrete chylomicrons into the lymph, leading to lipid accumulation and characteristic mucosal changes in the small intestine. Unlike ABL and Ho-HBL, CMRD does not cause acanthocytosis, retinitis pigmentosa, or severe neurological symptoms.<ref name=":1" />
==== Familial chylomicronemia syndrome (FCS) ====
'''[[Familial chylomicronemia syndrome]]''' (FCS), also known as '''Type I hyperlipoproteinemia''', is characterized by massive [[hypertriglyceridemia]], abdominal pain, pancreatitis, [[Xanthoma|eruptive xanthomas]], and [[hepatosplenomegaly]]. This condition is caused by mutations in genes such as LPL, APOC-II, APOA-V, LMF1, and GPIHBP1, which are involved in the regulation of triglyceride-rich lipoprotein catabolism. Patients with FCS show significantly elevated fasting concentrations of chylomicrons and do not typically develop premature atherosclerosis due to the large size of chylomicrons preventing their traversal through the vascular endothelial barrier. Diagnosis is confirmed by [[DNA sequencing]] for pathogenic mutations in these genes.<ref name=":1" />
== References ==
{{Reflist}}
▲{{Lipoproteins}}
{{Portal bar|Biology}}
▲[[Category:Lipoproteins]]
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