Effect of hyperthyroidism on hepatic lipogenesis in rats: studies in vivo and in vitro.
Lipogenic rates (measured with 3H2O) in hepatocytes from fed or starved euthyroid rats were similar in magnitude to those measured in livers in vivo. Hepatic lipogenesis in vivo in fed triiodothyronine (T3)-treated rats was greater than in fed control rats, but rates in vitro were only 16% of those of control rats. It is concluded that hepatic lipogenesis in vivo in T3-treated rats utilizes precursors from extrahepatic tissues. Glycogen depletion of hepatocytes from fed control rats decreased lipogenesis, and rates were then similar to those in hepatocytes from fed T3-treated rats. Addition of lactate (2 mmol/l) and pyruvate (0.2 mmol/l) had little stimulatory effect on lipogenesis in hepatocytes from fed control rats, but increased lipogenesis in glycogen-depleted hepatocytes (by 86%), hepatocytes from starved rats (by 25%) and hepatocytes from T3-treated rats (by 60%). In the presence of lactate and pyruvate, 3-mercaptopicolinate (3-MPA) (an inhibitor of gluconeogenesis) did not affect lipogenesis in hepatocytes from fed control rats but substantially increased lipogenesis in hepatocytes from starved euthyroid rats or fed hyperthyroid rats. Thus, in hepatocytes from starved euthyroid rats or fed hyperthyroid rats gluconeogenesis competes with lipogenesis for available precursors (lactate and pyruvate). In contrast, in fed rats carbon flux is predominantly towards lipogenesis. Effects of 3-MPA in the presence of lactate and pyruvate were much less in glycogen-depleted cells from fed rats than in hepatocytes from starved or T3-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D005260:Female; D006980:Hyperthyroidism / Q000378:metabolism*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010848:Picolinic Acids / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000494:pharmacology
D007773:Lactates; D008055:Lipids; D010848:Picolinic Acids; D011773:Pyruvates; D014284:Triiodothyronine; D019344:Lactic Acid; C008363:3-mercaptopicolinic acid; D019289:Pyruvic Acid