Hormonal regulation of lipogenesis in human diploid fibroblasts from normal subjects and from patients with familial hypertriglyceridaemia.

Lipogenesis has been investigated in diploid fibroblasts derived from patients with familial hypertriglyceridaemia (FHT) and compared with cells from healthy persons. There was no difference in acetyl-CoA carboxylase activity in both cell types. Incorporation of [2-14C]-acetate into triglyceride fatty acids was slightly increased (34%) by the FHT lines. Addition of triiodothyronine caused a marked rise in [2-14C]-acetate incorporation by the FHT lines whereas the normal lines exhibited only control values. Maximal rise in [2-14C]-acetate incorporation was obtained with 5 micrograms/ml for 72 h. Under these conditions, acetate incorporation by the FHT lines was 220% of the controls, compared with 94% by the normal lines. Measurements of acetyl-CoA carboxylase specific activity supported the results obtained with measurements of acetate incorporation into triglyceride fatty acids. Individual FHT lines differ much in their quantitative answer to thyroid hormones, although the described effects were obtained with all eight lines under study. Insulin increased acetyl-CoA carboxylase activity and incorporation of [2-14C]-acetate in lipids in both cell types, but with no difference between normal and FHT lines. The results seem to reflect a higher lipogenic capacity of the hypertriglyceridaemic fibroblasts compared with normal cells.