In vivo metabolism of apolipoproteins A-IV and A-I associated with high density lipoprotein in normolipidemic subjects

Malmendier, Claude; Lontie, J-F.; Lagrost, Laurent; Delcroix, Claude; Dubois, D.Y.; Gambert, Philippe

doi:10.1016/s0022-2275(20)42032-2

Cited by 19 publications

(8 citation statements)

References 30 publications

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“…Chylomicrons then travel through the lymph and enter systemic circulation via the thoracic duct ( Figure 7A , step 2). Once in circulation, APOA4 detaches from the chylomicron surface and transfers to, but not from, HDL, as has been shown in humans using radiolabeled APOA4 injected into plasma on the surface of chylomicrons ( 30 , 32 ). In vitro studies suggest that this APOA4 on chylomicrons is transferred to HDL in exchange for APOC2 ( Figure 7A , step 3) ( 33 , 34 ), resulting in the generation of APOA4-containing HDL ( Figure 7A , step 4).…”

Section: Discussionmentioning

confidence: 77%

“…Our APOA4 kinetic findings are consistent with previous studies of APOA4 metabolism on HDL. In addition to our preliminary kinetic study, which analyzed the metabolism of APOA4 on alpha3 and prebeta HDL ( 7 ), only 2 previous studies have analyzed APOA4 metabolism in HDL ( 30 , 32 ). Using exogenous radiolabeled APOA4, these studies found that the FCR of APOA4 on HDL was 0.62 ( 30 ) and 0.70 pool/d ( 32 ), similar to what we found for APOA4 on large HDL (0.78–0.84 pools/d) ( Figure 3E ).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike APOA4 on chylomicrons, APOA4 appears to be a stable constituent of HDL ( 31 ). Thus, APOA4 may transfer to, but not from, HDL ( 30 , 32 ).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Several studies have examined the metabolism of APOA4 in humans ( 7 , 30 , 32 , 48 – 50 ). But only 2 studies have analyzed APOA4 metabolism specifically in total HDL ( 30 , 32 ) and 1 in alpha3 and prebeta HDL, the HDL sizes in which APOA4 is most abundant ( 7 ). In the present study, we capitalized on technological advances of high-resolution targeted mass spectrometry ( 51 ) to determine the metabolism of APOA4 not only in alpha3 and prebeta but also in the larger HDL sizes (alpha0, 1, 2) in which APOA4 is approximately 100-fold less abundant than that of APOA4 on prebeta ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

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The distinct metabolism between large and small HDL indicates unique origins of human apolipoprotein A4

Andraski¹,

Singh²,

Higashi³

et al. 2023

JCI Insight

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Apolipoprotein A4’s (APOA4’s) functions on HDL in humans are not well understood. A unique feature of APOA4 is that it is an intestinal apolipoprotein secreted on HDL and chylomicrons. The goal of this study was to gain a better understanding of the origin and function of APOA4 on HDL by studying its metabolism across 6 HDL sizes. Twelve participants completed a metabolic tracer study. HDL was isolated by APOA1 immunopurification and separated by size. Tracer enrichments for APOA4 and APOA1 were determined by targeted mass spectrometry, and metabolic rates were derived by compartmental modeling. APOA4 metabolism on small HDL (alpha3, prebeta, and very small prebeta) was distinct from that of APOA4 on large HDL (alpha0, 1, 2). APOA4 on small HDL appeared in circulation by 30 minutes and was relatively rapidly catabolized. In contrast, APOA4 on large HDL appeared in circulation later (1–2 hours) and had a much slower catabolism. The unique metabolic profiles of APOA4 on small and large HDL likely indicate that each has a distinct origin and function in humans. This evidence supports the notion that APOA4 on small HDL originates directly from the small intestine while APOA4 on large HDL originates from chylomicron transfer.

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