Regulation of Lipogenesis and the Total Activities of Lipogenic Enzymes in a Primary Culture of Hepatocytes from Prenatal and Early Postnatal Chicks

Hepatocytes prepared from the livers of 18- or 19-day-old chick embryos and maintained in culture medium containing serum for 3 days exhibited marked induction of the lipogenic pathway. Incorporation of [U-14C]glucose into fatty acids and the total activities of malic enzyme, fatty acid synthetase, and ATP-citrate lyase increased by 1000-, 47-, 21-, and 4.5-fold, respectively. When l-triiodothyronine was added to the culture medium, the activities increased a total of 2500-, 140-, 40-, and 8-fold, respectively. The increases in the rate of fatty acid synthesis and total activity of malic enzyme were inhibited by bovine serum albumin, human thyroxin-binding prealbumin, and rabbit anti-thyroxin serum. Inhibition was reversed by adding a large amount of l-triiodothyronine. Thus, thyroid hormone was a major serum factor causing induction of the lipogenic pathway. Oxidation of [1-14C]acetate to CO2 and the total activity of NADP-isocitrate dehydrogenase were not affected by incubating the cells with or without l-triiodothyronine. The activity of lactate dehydrogenase decreased during the culture period. This induction of the lipogenesis pathway quantitatively mimics changes in the pathway which occur when newly hatched chicks are fed a high carbohydrate mash diet. Glucagon, cAMP, and free stearate also inhibited the induction of lipogenesis and its associated enzymes. These compounds also inhibit fatty acid synthesis and elevate fatty acyl-CoA levels in freshly prepared hepatocytes. Hence, glucagon and free fatty acids exert both long and short term regulation over fatty acid synthesis, possibly via changes in the intracellular concentration of fatty acyl-CoA.