BACKGROUND Comparable to commercial expensive high-fat diets, cholesterol-cholate-butterfat (CCB) diet has also been used to induce hyperlipidemia in rats. Our objective was to explore its influence on multiple organs. Consequence of fasting was also analysed. METHODS Rats in groups 1 and 2 received normal diet (ND) whereas groups 3 and 4 received CCB-diet. Food was withdrawn daily for two hours from groups 2 (ND-F) and 4 (CCB-F). Blood was collected at fourth and sixth week for biochemical estimation; Morris water maze was done in the sixth week for learning ability and memory; after which aortae were isolated for vascular reactivity. RESULTS Apart from hyperlipidemia, CCB also induced hyperglycemia with marked increase in hepatic enzymes: gamma-glutamyl transferase (GGT), alanine and aspartate aminotransferase (ALT and AST); and vascular biomarkers: uric acid (UA), phosphorus and alkaline phosphatase (ALP). Isolated aortae, pre-contracted with phenylephrine, were less responsive to acetylcholine indicating endothelial dysfunction--serum nitric oxide (NO) production was limited with subsequent inhibition of endothelial NO synthase. CCB diet also compromised learning ability. CCB-coupled fasting potentiated hyperlipidemia but prevented memory-loss. CONCLUSIONS We introduce CCB-diet for multi-organ dysfunction in rats, and propose its use for research on cardiovascular diseases and associated manifestations involving immense interplay of integrated pathways.