Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen. / Yang, Ye; Beigneux, Anne P.; Song, Wenxin; Nguyen, Le Phuong; Jung, Hyesoo; Tu, Yiping; Weston, Thomas A.; Tran, Caitlyn M.; Xie, Katherine; Yu, Rachel G.; Tran, Anh P.; Miyashita, Kazuya; Nakajima, Katsuyuki; Murakami, Masami; Chen, Yan Q.; Zhen, Eugene Y.; Kim, Joonyoung R.; Kim, Paul H.; Birrane, Gabriel; Tontonoz, Peter; Ploug, Michael; Konrad, Robert J.; Fong, Loren G.; Young, Stephen G.

In: Journal of Clinical Investigation, Vol. 133, No. 23, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Yang, Y, Beigneux, AP, Song, W, Nguyen, LP, Jung, H, Tu, Y, Weston, TA, Tran, CM, Xie, K, Yu, RG, Tran, AP, Miyashita, K, Nakajima, K, Murakami, M, Chen, YQ, Zhen, EY, Kim, JR, Kim, PH, Birrane, G, Tontonoz, P, Ploug, M, Konrad, RJ, Fong, LG & Young, SG 2023, 'Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen', Journal of Clinical Investigation, vol. 133, no. 23. https://doi.org/10.1172/JCI172600

APA

Yang, Y., Beigneux, A. P., Song, W., Nguyen, L. P., Jung, H., Tu, Y., Weston, T. A., Tran, C. M., Xie, K., Yu, R. G., Tran, A. P., Miyashita, K., Nakajima, K., Murakami, M., Chen, Y. Q., Zhen, E. Y., Kim, J. R., Kim, P. H., Birrane, G., ... Young, S. G. (2023). Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen. Journal of Clinical Investigation, 133(23). https://doi.org/10.1172/JCI172600

Vancouver

Yang Y, Beigneux AP, Song W, Nguyen LP, Jung H, Tu Y et al. Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen. Journal of Clinical Investigation. 2023;133(23). https://doi.org/10.1172/JCI172600

Author

Yang, Ye ; Beigneux, Anne P. ; Song, Wenxin ; Nguyen, Le Phuong ; Jung, Hyesoo ; Tu, Yiping ; Weston, Thomas A. ; Tran, Caitlyn M. ; Xie, Katherine ; Yu, Rachel G. ; Tran, Anh P. ; Miyashita, Kazuya ; Nakajima, Katsuyuki ; Murakami, Masami ; Chen, Yan Q. ; Zhen, Eugene Y. ; Kim, Joonyoung R. ; Kim, Paul H. ; Birrane, Gabriel ; Tontonoz, Peter ; Ploug, Michael ; Konrad, Robert J. ; Fong, Loren G. ; Young, Stephen G. / Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen. In: Journal of Clinical Investigation. 2023 ; Vol. 133, No. 23.

Bibtex

@article{e5e01920447e457baa424c4b5c0d8994,
title = "Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen",
abstract = "Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5-/- mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific mAbs, the binding of LPL Abs to heart and BAT capillaries (relative to CD31 or GPIHBP1 Abs) was reduced in Apoa5-/- mice. LPL levels in the postheparin plasma were also lower in Apoa5-/- mice. We suspected that a recent biochemical observation - that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity - could be related to the low intracapillary LPL levels in Apoa5-/- mice. We showed that an ANGPTL3/8-specific mAb (IBA490) and APOA5 normalized plasma triglyceride (TG) levels and intracapillary LPL levels in Apoa5-/- mice. We also showed that ANGPTL3/8 detached LPL from heparan sulfate proteoglycans and GPIHBP1 on the surface of cells and that the LPL detachment was blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5-/- mice and further illuminate the molecular mechanisms that regulate plasma TG metabolism.",
keywords = "Endothelial cells, Lipoproteins, Metabolism, Mouse models, Vascular Biology",
author = "Ye Yang and Beigneux, {Anne P.} and Wenxin Song and Nguyen, {Le Phuong} and Hyesoo Jung and Yiping Tu and Weston, {Thomas A.} and Tran, {Caitlyn M.} and Katherine Xie and Yu, {Rachel G.} and Tran, {Anh P.} and Kazuya Miyashita and Katsuyuki Nakajima and Masami Murakami and Chen, {Yan Q.} and Zhen, {Eugene Y.} and Kim, {Joonyoung R.} and Kim, {Paul H.} and Gabriel Birrane and Peter Tontonoz and Michael Ploug and Konrad, {Robert J.} and Fong, {Loren G.} and Young, {Stephen G.}",
year = "2023",
doi = "10.1172/JCI172600",
language = "English",
volume = "133",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "23",

}

RIS

TY - JOUR

T1 - Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen

AU - Yang, Ye

AU - Beigneux, Anne P.

AU - Song, Wenxin

AU - Nguyen, Le Phuong

AU - Jung, Hyesoo

AU - Tu, Yiping

AU - Weston, Thomas A.

AU - Tran, Caitlyn M.

AU - Xie, Katherine

AU - Yu, Rachel G.

AU - Tran, Anh P.

AU - Miyashita, Kazuya

AU - Nakajima, Katsuyuki

AU - Murakami, Masami

AU - Chen, Yan Q.

AU - Zhen, Eugene Y.

AU - Kim, Joonyoung R.

AU - Kim, Paul H.

AU - Birrane, Gabriel

AU - Tontonoz, Peter

AU - Ploug, Michael

AU - Konrad, Robert J.

AU - Fong, Loren G.

AU - Young, Stephen G.

PY - 2023

Y1 - 2023

N2 - Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5-/- mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific mAbs, the binding of LPL Abs to heart and BAT capillaries (relative to CD31 or GPIHBP1 Abs) was reduced in Apoa5-/- mice. LPL levels in the postheparin plasma were also lower in Apoa5-/- mice. We suspected that a recent biochemical observation - that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity - could be related to the low intracapillary LPL levels in Apoa5-/- mice. We showed that an ANGPTL3/8-specific mAb (IBA490) and APOA5 normalized plasma triglyceride (TG) levels and intracapillary LPL levels in Apoa5-/- mice. We also showed that ANGPTL3/8 detached LPL from heparan sulfate proteoglycans and GPIHBP1 on the surface of cells and that the LPL detachment was blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5-/- mice and further illuminate the molecular mechanisms that regulate plasma TG metabolism.

AB - Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5-/- mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific mAbs, the binding of LPL Abs to heart and BAT capillaries (relative to CD31 or GPIHBP1 Abs) was reduced in Apoa5-/- mice. LPL levels in the postheparin plasma were also lower in Apoa5-/- mice. We suspected that a recent biochemical observation - that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity - could be related to the low intracapillary LPL levels in Apoa5-/- mice. We showed that an ANGPTL3/8-specific mAb (IBA490) and APOA5 normalized plasma triglyceride (TG) levels and intracapillary LPL levels in Apoa5-/- mice. We also showed that ANGPTL3/8 detached LPL from heparan sulfate proteoglycans and GPIHBP1 on the surface of cells and that the LPL detachment was blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5-/- mice and further illuminate the molecular mechanisms that regulate plasma TG metabolism.

KW - Endothelial cells

KW - Lipoproteins

KW - Metabolism

KW - Mouse models

KW - Vascular Biology

U2 - 10.1172/JCI172600

DO - 10.1172/JCI172600

M3 - Journal article

C2 - 37824203

AN - SCOPUS:85178649108

VL - 133

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 23

ER -

ID: 378951961