Palmitic rich interesterified (IE) fats exert detrimental effects on atherogenicity in animals but less significant effects in animal and human plasma lipids. Thus, it is important to investigate the role IE fats on lipid subfractions and hepatic gene expression involved in lipoprotein regulation. F1B male Golden Syrian hamsters (Mesocricetus auratus) were fed high-fat diets ad libitum containing 0.1% dietary cholesterol and 30% energy from dietary fat, either native or IE fats namely palm olein (PO), chemically IE palm olein (CIEPO), sal fat blend (SFB) and chemically IE sal fat blend (CIESFB) for 12 weeks. Plasma lipid profiles, low density lipoprotein (LDL) and high density lipoprotein (HDL) sub-fractions and hepatic gene expression levels were determined. PO and CIEPO fed hamsters had 38% and 27% higher plasma HDL levels compared to SFB and CIESFB, respectively. Animals given PO diet had greater proportion of the larger HDL particles than SFB and CIESFB fed animals (p<0.05). Whereas, animals fed with SFB and CIESFB had greater proportion of larger LDL particles compared to both palmitic counterparts. All diets upregulated genes involved in liver fat accumulation such as CXCL16, VLDR and APO E. SFB diet showed significant (p<0.05) 16-fold upregulation in CXCL16 gene. Gene expression for ABCA1, APO A1 and CETP were upregulated all groups in response of reverse cholesterol transport (RCT). Palmitic-rich diets presented significant upregulation in APO A1 gene (p<0.05). LDL metabolism related genes such as LDLR, PCSK9, APO B, CYP7A1, PCSK9 were downregulated in all diets. In conclusion, native and IE saturated high-fat diets, induce liver steatosis in hamsters as shown in CXCL16, VLDLR and APOE expression. In this condition, cholesterol clearance via RCT was activated with expression of related genes such as ABCA1, LCAT, APO A1 and CETP. However, these effects on plasma level HDL cholesterol and large HDL sub-fractions were only seen in palmitic rich fats. Whereas, LDLR mediated cholesterol clearance was downregulated with suppression of LDLR gene with similar effects on plasma LDL in all diets.