Fructose-induced hypertriglyceridemia in rhesus macaques is attenuated with fish oil or ApoC3 RNA interference

Abstract

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.-Butler, A.

Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi

“…Finally, we report on the effects of inhibiting hepatic ANGPTL3 expression with RNAi on plasma lipid/lipoprotein profiles. This study includes comparisons with the responses to inhibiting hepatic APOC3 concentrations, which have been reported previously (30).…”

“…Nonhuman primates are an important resource for the translational research of novel therapies against obesityrelated metabolic diseases (26,27). Previous studies have demonstrated that rhesus macaques provided with fructose or high-fructose corn syrup (HFCS) supplements (300-600 kcal/d) rapidly gain weight and develop features of metabolic syndrome (insulin resistance, hypertriglyceridemia, and increased APOC3) (28)(29)(30). Using this model, we recently reported that an RNAi construct targeting hepatic APOC3 expression reduces plasma TG concentrations (30).…”

“…Previous studies have demonstrated that rhesus macaques provided with fructose or high-fructose corn syrup (HFCS) supplements (300-600 kcal/d) rapidly gain weight and develop features of metabolic syndrome (insulin resistance, hypertriglyceridemia, and increased APOC3) (28)(29)(30). Using this model, we recently reported that an RNAi construct targeting hepatic APOC3 expression reduces plasma TG concentrations (30). Moreover, elevations of plasma TG concentrations during fructose consumption are positively correlated with increases of circulating APOC3 concentrations (30).…”

“…Using this model, we recently reported that an RNAi construct targeting hepatic APOC3 expression reduces plasma TG concentrations (30). Moreover, elevations of plasma TG concentrations during fructose consumption are positively correlated with increases of circulating APOC3 concentrations (30). However, the impact of dietary composition and diet-induced obesity/metabolic dysfunction on plasma ANGPTL3 concentrations has not been investigated.…”

“…The results of a large (n = 59) study into the effects of fructose supplements on weight gain and indices of insulin resistance [fasting insulin, fasting glucose, and homeostatic model assessment of insulin resistance (HOMA-IR)] and dyslipidemia have previously been reported (28)(29)(30)(31). These studies reported rapid gains in body weight, fasting hyperinsulinemia, fasting hypertriglyceridemia, and elevated plasma APOC3 concentrations with fructose consumption that are largely prevented by fish oil supplementation (29,30). The current investigation examined dietary effects and relationships between plasma concentrations of ANGPTL3 and indices of insulin resistance, systemic inflammation, and lipoprotein metabolism.…”