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Ritonavir impairs lipoprotein lipase-mediated lipolysis and decreases uptake of fatty acids in adipose tissue.
Arterioscler Thromb Vasc Biol. 2006 Jan; 26(1):124-9.AT

Abstract

OBJECTIVE

The use of the HIV protease inhibitor ritonavir (RTV) is frequently associated with hypertriglyceridemia and lipodystrophy. The aim of our study was to determine the mechanism underlying the observed hypertriglyceridemia.

METHODS AND RESULTS

Feeding female APOE*3-Leiden transgenic mice a Western-type diet supplemented with RTV (35 mg/kg per day) for 2 weeks resulted in a 2-fold increase in fasting plasma triglyceride (TG) levels, which was specific for very low-density lipoprotein (VLDL). RTV did not change the hepatic VLDL-TG production. Instead, RTV did increase the postprandial TG response to an oral fat load (area under the curve, 25.5+/-12.1 versus 13.8+/-6.8 mmol/L per hour in controls; P<0.05). Likewise, RTV hampered the plasma clearance of intravenously injected glycerol tri[3H]oleate-labeled VLDL-like emulsion particles (half time, 19.3+/-10.5 versus 5.0+/-1.3 minutes in controls; P<0.05) associated with a decrease of 44% in plasma lipoprotein lipase activity. Accordingly, RTV decreased the uptake of TG-derived fatty acids (FAs) into adipose tissue, as well as the uptake of albumin-bound FA.

CONCLUSIONS

We conclude that RTV causes hypertriglyceridemia via decreased lipoprotein lipase-mediated clearance of VLDL-TG. In addition, RTV specifically impairs the uptake of FA in adipose tissue, which may contribute to the lipodystrophy that is frequently observed in HIV-infected subjects on antiretroviral therapy.

Authors+Show Affiliations

Department of Endocrinology and Diabetes, Leiden University Medical Center, Leiden, The Netherlands. A.M.den_Boer@lumc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16269669

Citation

den Boer, Marion A M., et al. "Ritonavir Impairs Lipoprotein Lipase-mediated Lipolysis and Decreases Uptake of Fatty Acids in Adipose Tissue." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 1, 2006, pp. 124-9.
den Boer MA, Berbée JF, Reiss P, et al. Ritonavir impairs lipoprotein lipase-mediated lipolysis and decreases uptake of fatty acids in adipose tissue. Arterioscler Thromb Vasc Biol. 2006;26(1):124-9.
den Boer, M. A., Berbée, J. F., Reiss, P., van der Valk, M., Voshol, P. J., Kuipers, F., Havekes, L. M., Rensen, P. C., & Romijn, J. A. (2006). Ritonavir impairs lipoprotein lipase-mediated lipolysis and decreases uptake of fatty acids in adipose tissue. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(1), 124-9.
den Boer MA, et al. Ritonavir Impairs Lipoprotein Lipase-mediated Lipolysis and Decreases Uptake of Fatty Acids in Adipose Tissue. Arterioscler Thromb Vasc Biol. 2006;26(1):124-9. PubMed PMID: 16269669.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ritonavir impairs lipoprotein lipase-mediated lipolysis and decreases uptake of fatty acids in adipose tissue. AU - den Boer,Marion A M, AU - Berbée,Jimmy F P, AU - Reiss,Peter, AU - van der Valk,Marc, AU - Voshol,Peter J, AU - Kuipers,Folkert, AU - Havekes,Louis M, AU - Rensen,Patrick C N, AU - Romijn,Johannes A, Y1 - 2005/11/03/ PY - 2005/11/5/pubmed PY - 2006/2/4/medline PY - 2005/11/5/entrez SP - 124 EP - 9 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 26 IS - 1 N2 - OBJECTIVE: The use of the HIV protease inhibitor ritonavir (RTV) is frequently associated with hypertriglyceridemia and lipodystrophy. The aim of our study was to determine the mechanism underlying the observed hypertriglyceridemia. METHODS AND RESULTS: Feeding female APOE*3-Leiden transgenic mice a Western-type diet supplemented with RTV (35 mg/kg per day) for 2 weeks resulted in a 2-fold increase in fasting plasma triglyceride (TG) levels, which was specific for very low-density lipoprotein (VLDL). RTV did not change the hepatic VLDL-TG production. Instead, RTV did increase the postprandial TG response to an oral fat load (area under the curve, 25.5+/-12.1 versus 13.8+/-6.8 mmol/L per hour in controls; P<0.05). Likewise, RTV hampered the plasma clearance of intravenously injected glycerol tri[3H]oleate-labeled VLDL-like emulsion particles (half time, 19.3+/-10.5 versus 5.0+/-1.3 minutes in controls; P<0.05) associated with a decrease of 44% in plasma lipoprotein lipase activity. Accordingly, RTV decreased the uptake of TG-derived fatty acids (FAs) into adipose tissue, as well as the uptake of albumin-bound FA. CONCLUSIONS: We conclude that RTV causes hypertriglyceridemia via decreased lipoprotein lipase-mediated clearance of VLDL-TG. In addition, RTV specifically impairs the uptake of FA in adipose tissue, which may contribute to the lipodystrophy that is frequently observed in HIV-infected subjects on antiretroviral therapy. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/16269669/Ritonavir_impairs_lipoprotein_lipase_mediated_lipolysis_and_decreases_uptake_of_fatty_acids_in_adipose_tissue_ L2 - https://www.ahajournals.org/doi/10.1161/01.ATV.0000194073.87647.10?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -