The high-fat high-fructose hamster as an animal model for niacin's biological activities in humans

Abstract

Objective: Niacin has been used for more than 50 years to treat dyslipidemia, yet the mechanisms underlying its lipid-modifying effects remain unknown, a situation stemming at least in part from a lack of validated animal models. The objective of this study was to determine if the dyslipidemic hamster could serve as such a model.

Materials/methods: Dyslipidemia was induced in Golden Syrian hamsters by feeding them a high-fat, high-cholesterol, and high-fructose (HF/HF) diet. The effect of high-dose niacin treatment for 18 days and 28 days on plasma lipid levels and gene expression was measured.

Results: Niacin treatment produced significant decreases in plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and free fatty acids (FFA), but had no measureable effect on high-density lipoprotein cholesterol (HDL-C) in the dyslipidemic hamster. Niacin treatment also produced significant increases in hepatic adenosine ATP-Binding Cassette A1 (ABCA1) mRNA, ABCA1 protein, apolipoprotein A-I (Apo A-I) mRNA, and adipose adiponectin mRNA in these animals.

Conclusions: With the exception of HDL-C, the lipid effects of niacin treatment in the dyslipidemic hamster closely parallel those observed in humans. Moreover, the effects of niacin treatment on gene expression of hepatic proteins related to HDL metabolism are similar to those observed in human cells in culture. The HF/HF-fed hamster could therefore serve as an animal model for niacin's lowering of proatherogenic lipids and mechanisms of action relative to lipid metabolism.

Keywords: ABCA1; AIM-HIGH; ARBITER; Apo A-I; ApoB48; Arterial Biology for the Investigation of Treatment Effects of Reducing Cholesterol; Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes; CETP; CLAS; DGAT2; FATS; FFA; Familial Atherosclerosis Treatment Study; GS; Golden Syrian; HATS; HDL; HDL-Atherosclerosis Treatment Study; HDL-C; HF/HF; HPS2-THRIVE; Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events; LDL; LDL-C; LDLr; LXRα; Lipid metabolism; NC; SR-B1; TC; TG; The Cholesterol-Lowering Atherosclerosis Study; VLDL; adenosine ATP-Binding Cassette A1; apoE; apolipoprotein A-I; apolipoprotein B48; apolipoprotein E; cholesteryl ester transfer protein; diacylglycerol acyltransferase 2; free fatty acids; high-density lipoprotein; high-fat, high-cholesterol, and high-fructose; liver x receptor-alpha; low-density lipoprotein; low-density lipoprotein receptor; normal chow; scavenger receptor class B member 1.; total cholesterol; triglycerides; very low-density lipoprotein.