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Publication
Fructose-induced hypertriglyceridemia in rhesus macaques is attenuated with fish
oil or ApoC3 RNA interference.
Authors Butler AA, Price CA, Graham JL, Stanhope KL, King S, Hung YH, Sethupathy P, Wong
S, Hamilton J, Krauss RM, Bremer AA, Havel PJ
Submitted By Submitted Externally on 4/8/2019
Status Published
Journal Journal of lipid research
Year 2019
Date Published 4/1/2019
Volume : Pages 60 : 805 - 818
PubMed Reference 30723097
Abstract Dyslipidemia and insulin resistance are significant adverse outcomes of
consuming high-sugar diets. Conversely, dietary fish oil (FO) reduces plasma
lipids. Diet-induced dyslipidemia in a rhesus model better approximates the
pathophysiology of human metabolic syndrome (MetS) than rodent models. Here, we
investigated relationships between metabolic parameters and hypertriglyceridemia
in rhesus macaques consuming a high-fructose diet (n = 59) and determined the
effects of FO supplementation or RNA interference (RNAi) on plasma ApoC3 and
triglyceride (TG) concentrations. Fructose supplementation increased body
weight, fasting insulin, leptin, TGs, and large VLDL particles and reduced
adiponectin concentrations (all P < 0.001). In multiple regression analyses,
increased plasma ApoC3 was the most consistent and significant variable related
to diet-induced hypertriglyceridemia. FO supplementation, which attenuated
increases of plasma TG and ApoC3 concentrations, reversed fructose-induced
shifts of lipoprotein particle size toward IDL and VLDL, a likely mechanism
contributing to beneficial metabolic effects, and reduced hepatic expression of
genes regulated by the SREBP pathway, particularly acetyl-CoA carboxylase.
Furthermore, RNAi-mediated ApoC3 inhibition lowered plasma TG concentrations in
animals with diet-induced hypertriglyceridemia. In summary, ApoC3 is an
important independent correlate of TG-rich lipoprotein concentrations in rhesus
macaques consuming a high-fructose diet. ApoC3 is a promising therapeutic target
for hypertriglyceridemia in patients with MetS and diabetes.





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