Effect of diet composition and fasting on lipogenesis in lean and polygenic obese mice

A line of mice was developed which exhibited spontaneous obesity when fed commercial laboratory ration low in fat content. Obese mice were compared to a nonobese related line to determine whether energy source in the diet would affect onset of obesity. Experimental diets-beef tallow (38% of calories as beef fat and 2% as corn oil), corn oil (40% corn oil) or low-fat (2% corn oil)-were instituted ad libitum at the time of weaning. When the mice reached 6 months of age, lipogenesis was investigated by injecting intravenously³H₂O and glucose-U-¹⁴C.³H₂O and glucose-U-¹⁴C incorporation into fatty acids of fed mice was greater for obese than for lean mice. Fatty acid synthesis was inhibited by high-fat diets compared to low-fat diet in both lines. Of the 2 high-fat diets, the corn oil diet inhibited fatty acid synthesis about twice as much as beef tallow diet. There was no line effect on tritium incorporation into cholesterol. Cholesterol synthesis from glucose-U-¹⁴C was greater in obese than lean mice. Diets had no effect on tritium and glucose-U-¹⁴C incorporation into cholesterol. Fasting reduced fatty acid synthesis in all mice, but total body fatty acid synthesis was not affected by lines or dietary treatment under fasted conditions. These data suggest that degree of lipogenesis, in part, explains obesity. A failure of inhibition of lipogenesis or an enhanced efficiency in fat deposition by feeding beef tallow compared to corn oil diet may explain the fact that lean mice fed the beef tallow diet tended to be more obese that lean mice fed corn oil or low-fat diets.