BackgroundIt is generally accepted that excessive fat intake has undesirable effects on the energy metabolism of our body. Dietary amino acid composition is also critical to the regulation of lipid metabolism. ObjectiveTo investigate whether high fat diets (HFDs) with different amino acid deficiencies lead to different metabolic outcomes. MethodsSix-week-old male Wistar rats were fed either a control diet (CN; 3.7 kcal/g, 12% calories from fat) or HFDs (5.1 kcal/g, 60% calories from fat) with seven different amino acid compositions (control or methionine-, arginine-, histidine-, lysine-, threonine-, or branched-chain amino acids (BCAAs)-deficient), for 7 days. Tissue weights and lipid accumulation in the liver, skeletal muscle, and adipose tissue were measured and serum biochemical parameters were analyzed. ResultsWhile the food intake of the HFD groups was a bit less than that of the CN group, the total calorie intakes were comparable among the groups, except for histidine- and BCAA-deficient groups. In rats fed a HFD with a control amino acid composition (HFCN), dramatic increase in triglyceride (TG) accumulation in the liver and serum low-density lipoprotein-cholesterol (LDL-C) level were observed compared with the CN group. However, when the arginine-content in the diet was reduced, liver TG accumulation was completely inhibited, with no apparent effects on serum lipoprotein-cholesterol levels. Meanwhile, deficiency of the other amino acids, such as threonine, reversed HFD-induced upregulation of serum LDL-C. ConclusionsEven though the rats ingested an excessive amount of fat, neither ectopic fat accumulation nor dyslipidemia were always induced at least in the short term; hence, the consequent metabolic change was dependent on the dietary amino acid composition. These findings introduce an important perspective regarding HFD regimens in both scientific and clinical contexts.