Studies on lipogenesis in vivo: Fatty acid and cholesterol synthesis in hyperglycaemic-obese mice.

1. Lipogenesis has been studied in intact genetically obese mice by measuring the incorporation of a single oral dose of 250mg. of [U-(14)C]glucose into fatty acid and cholesterol in the liver and extrahepatic tissues. Studies were also carried out with [U-(14)C]glucose added to the diet and fed for 24hr. With either method of isotope administration, the conversion of [U-(14)C]glucose into fatty acid was greatly elevated in the livers of the obese mice. In contrast, conversion of the single dose of [(14)C]glucose into fatty acid in extrahepatic tissues of obese mice was only half that occurring in the non-obese litter mates. When [(14)C]glucose was given in the diet for 24hr. the total accumulation of labelled fatty acid in extrahepatic tissues of obese mice was slightly less than in the non-obese. Uptake of labelled glucose and conversion into fatty acid in adipose tissue of the obese mice decreased with age. 2. Conversion of the single dose of [(14)C]glucose into liver cholesterol was comparable in obese and non-obese mice fed on a purified low-fat diet. However, obese mice given this diet for 12 weeks accumulated 1.54% of cholesterol in the liver compared with 0.29% in the non-obese litter mates. This accumulation apparently resulted from a decrease in removal of cholesterol from the liver, rather than an increased synthesis. 3. Conversion of the single dose of [(14)C]glucose into extrahepatic fatty acid was decreased by 18hr. starvation proportionally as much in obese as in non-obese mice. The decrease in liver fatty acid synthesis caused by starvation also was considerable in obese mice, although somewhat less marked than in the non-obese. 4. The metabolic derangements in the liver could be more fundamental to the development of the obesity than the changes seen in extrahepatic tissues.