Inhibition of lipogenesis by vasopressin and angiotensin II in glycogen-depleted hepatocytes.
Vasopressin and angiotensin II inhibited lipogenesis (measured with 3H2O) in hepatocytes from fed rats. Inhibition was also observed with hepatocytes from fed rats which had been depleted of glycogen in vitro and incubated with lactate + pyruvate (5 mM + 0.5 mM) as substrates. The inhibitory actions of the hormones are therefore independent of hormone-mediated changes in glycogenolytic or glycolytic flux from glycogen, and thus the site(s) of hormone action must be subsequent to the formation of lactate. (-)Hydroxycitrate, a specific inhibitor of ATP-citrate lyase, decreased lipogenesis in hepatocytes from fed rats incubated with lactate + pyruvate by approx. 51% but had little effect on lipogenesis in glycogen-depleted hepatocytes similarly incubated. There was parallel inhibition of incorporation of 14C from [U-14C]lactate into fatty acid and lipogenesis as measured with 3H2O in each case. Thus depletion of glycogen, or conceivably the process of glycogen-depletion (incubation with dibutyryl cyclic AMP) causes a change in the rate-determining step(s) for lipogenesis from lactate. Vasopressin and angiotensin II also decreased lipogenesis and incorporation of 14C into fatty acids in glycogen-depleted hepatocytes provided with [U-14C]proline as opposed to [U-14C]-lactate. However, proline-stimulated lipogenesis was inhibited by (-)hydroxycitrate, and proline-stimulated lipogenesis and incorporation of 14C from [U-14C]-proline were not decreased in parallel by this inhibitor (inhibition of 52% and 85% respectively). It is inferred that lactate and proline stimulate lipogenesis by different mechanisms and incorporation of 14C from [U-14C]proline and [U-14C]lactate into fatty acid occurs via different routes.(ABSTRACT TRUNCATED AT 250 WORDS)
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D005260:Female; D006003:Glycogen / Q000502:physiology*; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology*
D002951:Citrates; D007773:Lactates; D008055:Lipids; D011773:Pyruvates; D014667:Vasopressins; D000804:Angiotensin II; D019344:Lactic Acid; D003994:Bucladesine; D019289:Pyruvic Acid; C007999:hydroxycitric acid; D006003:Glycogen; D011392:Proline