Ketone bodies, glucose and glutamine as lipogenic precursors in human diploid fibroblasts.

Abstract:

:Incorporation of [14C] from acetoacetate, D(-)- and L(+)-3-hydroxybutyrate, glucose, glutamine, acetate and palmitate in cellular lipids were studied in cultures in human diploid fibroblasts (HDF). The results showed that acetoacetate was 2-10 times more effective as a lipogenic precursor than was either D- or L-3-hydroxybutyrate. Its extent of incorporation into lipids was 2- to 8-fold more than the other precursors examined under conditions when the overall rates of nonsaponifiable and saponifiable lipogenesis as measured by 3H2O incorporation were essentially unchanged. Acetoacetate supported both saponifiable and nonsaponifiable lipid synthesis with half-saturation values (Km app.) of 185 microM and 30 microM, respectively. Glucose stimulated acetoacetate incorporation into lipids whereas, conversely, acetoacetate inhibited [14C]glucose incorporation into lipids. The presence of low density lipoproteins (LDL) cholesterol (40 microgram cholesterol/mL) inhibited the incorporation of [14C] from acetoacetate 56% into nonsaponifiable lipids; the inhibition was consistently higher (75%) when [14C]glucose or glutamine were the precursors. The loss of 3-hydroxy-3-methyl-glutaryl CoA (HMG CoA) reductase activity upon addition of LDL-cholesterol was greater than the suppression of [14C] incorporation from acetoacetate or glucose into nonsaponifiable lipids. In the presence of glucose, [14C]acetoacetate was incorporated into 3-beta OH sterols (digitonin precipitable) 7.7 +/- 1.1 times more effectively than was [14C]glucose. The results suggest that HDF would be a suitable model to investigate the effects of various precursors of HMG CoA on the rate of cholesterol biosynthesis.

journal_name

Lipids

journal_title

Lipids

authors

Reed WD,Zielke HR,Baab PJ,Ozand PT

doi

10.1007/BF02535063

subject

Has Abstract

pub_date

1981-09-01 00:00:00

pages

677-84

issue

9

eissn

0024-4201

issn

1558-9307

journal_volume

16

pub_type

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