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. 1972 Aug;128(5):1057–1067. doi: 10.1042/bj1281057

The regulation of glyceride synthesis in isolated white-fat cells. The effects of palmitate and lipolytic agents

E David Saggerson 1
PMCID: PMC1173993  PMID: 4345351

Abstract

1. 0.5mm-Palmitate stimulated incorporation of [U-14C]glucose into glyceride glycerol and fatty acids in normal fat cells in a manner dependent upon the glucose concentration. 2. In the presence of insulin the incorporation of 5mm-glucose into glyceride fatty acids was increased by concentrations of palmitate, adrenaline and 6-N-2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate up to 0.5mm, 0.5μm and 0.5mm respectively. Higher concentrations of these agents produced progressive decreases in the rate of glucose incorporation into fatty acids. 3. The effects of palmitate and lipolytic agents upon the measured parameters of glucose utilization were similar, suggesting that the effects of lipolytic agents are mediated through increased concentrations of free fatty acids. 4. In fat cells from 24h-starved rats, maximal stimulation of glucose incorporation into fatty acids was achieved with 0.25mm-palmitate. Higher concentrations of palmitate were inhibitory. In fat cells from 72h-starved rats, palmitate only stimulated glucose incorporation into fatty acids at high concentrations of palmitate (1mm and above). 5. The ability of fat cells to incorporate glucose into glyceride glycerol in the presence of palmitate decreased with increasing periods of starvation. 6. It is suggested that low concentrations of free fatty acids stimulate fatty acid synthesis from glucose by increasing the utilization of ATP and cytoplasmic NADH for esterification of these free fatty acids. When esterification of free fatty acids does not keep pace with their provision, inhibition of fatty acid synthesis occurs. Provision of free fatty acids far in excess of the esterification capacity of the cells leads to uncoupling of oxidative phosphorylation and a secondary stimulation of fatty acid synthesis from glucose.

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Selected References

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  1. Angel A., Desai K. S., Halperin M. L. Intracellular accumulation of free fatty acids in isolated white adipose cells. J Lipid Res. 1971 Jan;12(1):104–111. [PubMed] [Google Scholar]
  2. Angel A., Desai K. S., Halperin M. L. Reduction in adipocyte ATP by lipolytic agents: relation to intracellular free fatty acid accumulation. J Lipid Res. 1971 Mar;12(2):203–213. [PubMed] [Google Scholar]
  3. Angel A., Roncari D. A. The control of fatty acid esterification in a subcellular preparation of rat adipose tissue. Biochim Biophys Acta. 1967 Jun 6;137(3):464–474. doi: 10.1016/0005-2760(67)90127-0. [DOI] [PubMed] [Google Scholar]
  4. BALLY P. R., CAHILL G. F., Jr, LEBOEUF B., RENOLD A. E. Studies on rat adipose tissue in vitro. V. Effects of glucose and insulin on the metabolism of palmitate-1-C14. J Biol Chem. 1960 Feb;235:333–336. [PubMed] [Google Scholar]
  5. BRUCE H. M., PARKES A. S. Feeding and breeding of laboratory animals; a complete cubed diet for mice and rats. J Hyg (Lond) 1949 Jun;47(2):202–208. doi: 10.1017/s0022172400014479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bihler I., Jeanrenaud B. ATP content of isolated fat cells. Effects of insulin, ouabain, and lipolytic agents. Biochim Biophys Acta. 1970 May 5;202(3):496–506. doi: 10.1016/0005-2760(70)90120-7. [DOI] [PubMed] [Google Scholar]
  8. Blecher M. Evidence for the involvement of cyclic-3',5'-adenosine monophosphate in glucose utilization by isolated rat epididymal adipose cells. Biochem Biophys Res Commun. 1967 Jun 9;27(5):560–567. doi: 10.1016/s0006-291x(67)80024-x. [DOI] [PubMed] [Google Scholar]
  9. Blecher M., Merlino N. S., Ro'Ane J. T. Controle of the metabolism and lipolytic effects of cyclic 3',5'-adenosine monophosphate in adipose tissue by insulin, methyl xanthines, and nicotinic acid. J Biol Chem. 1968 Jul 25;243(14):3973–3977. [PubMed] [Google Scholar]
  10. Blecher M., Merlino N. S., Ro'Ane J. T., Flynn P. D. Independence of the effects of epinephrine, glucagon, and adrenocorticotropin on glucose utilization from those on lipolysis in isolated rat adipose cells. J Biol Chem. 1969 Jul 10;244(13):3423–3429. [PubMed] [Google Scholar]
  11. Blecher M., Ro'Ane J. T., Flynn P. D. Metabolism of dibutyryl cyclic adenosine 3',5'-monophosphate during its regulation of lipolysis and glucose oxidation in isolated rat epididymal adipocytes. J Biol Chem. 1970 Apr 25;245(8):1867–1870. [PubMed] [Google Scholar]
  12. Bray G. A. Effects of epinephrine, corticotropin, and thyrotropin on lipolysis and glucose oxidation in rat adipose tissue. J Lipid Res. 1967 Jul;8(4):300–307. [PubMed] [Google Scholar]
  13. Bray G. A., Goodman H. M. Effects of epinephrine on glucose transport and metabolism in adipose tissue of normal and hypothyroid rats. J Lipid Res. 1968 Nov;9(6):714–719. [PubMed] [Google Scholar]
  14. CAHILL G. F., Jr, LEBOEUF B., FLINN R. B. Studies on rat adipose tissue in vitro. VI. Effect of epinephrine on glucose metabolism. J Biol Chem. 1960 May;235:1246–1250. [PubMed] [Google Scholar]
  15. Chen R. F. Removal of fatty acids from serum albumin by charcoal treatment. J Biol Chem. 1967 Jan 25;242(2):173–181. [PubMed] [Google Scholar]
  16. Coore H. G., Denton R. M., Martin B. R., Randle P. J. Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones. Biochem J. 1971 Nov;125(1):115–127. doi: 10.1042/bj1250115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Cushman S. W. Structure-function relationships in the adipose cell. II. Pinocytosis and factors influencing its activity in the isolated adipose cell. J Cell Biol. 1970 Aug;46(2):342–353. doi: 10.1083/jcb.46.2.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Del Boca J., Flatt J. P. Fatty acid synthesis from glucose and acetate and the control of lipogenesis in adipose tissue. Eur J Biochem. 1969 Nov;11(1):127–134. doi: 10.1111/j.1432-1033.1969.tb00749.x. [DOI] [PubMed] [Google Scholar]
  19. Denton R. M., Halperin M. L. The control of fatty acid and triglyceride synthesis in rat epididymal adipose tissue. Roles of coenzyme A derivatives, citrate and L-glycerol 3-phosphate. Biochem J. 1968 Nov;110(1):27–38. doi: 10.1042/bj1100027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Denton R. M., Randle P. J. Measurement of flow of carbon atoms from glucose and glycogen glucose to glyceride glycerol and glycerol in rat heart and epididymal adipose tissue. Effects of insulin, adrenaline and alloxan-diabetes. Biochem J. 1967 Aug;104(2):423–434. doi: 10.1042/bj1040423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Denton R. M., Yorke R. E., Randle P. J. Measurement of concentrations of metabolites in adipose tissue and effects of insulin, alloxan-diabetes and adrenaline. Biochem J. 1966 Aug;100(2):407–419. doi: 10.1042/bj1000407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. EVANS W. H., MUELLER P. S. EFFECTS OF PALMITATE ON THE METABOLISM OF LEUKOCYTES FROM GUINEA PIG EXUDATE. J Lipid Res. 1963 Jan;4:39–45. [PubMed] [Google Scholar]
  23. FLATT J. P., BALL E. G. STUDIES ON THE METABOLISM OF ADIPOSE TISSUE. XV. AN EVALUATION OF THE MAJOR PATHWAYS OF GLUCOSE CATABOLISM AS INFLUENCED BY INSULIN AND EPINEPHRINE. J Biol Chem. 1964 Mar;239:675–685. [PubMed] [Google Scholar]
  24. Flatt J. P., Ball E. G. Studies on the metabolism of adipose tissue. XIX. An evaluation of the major pathways of glucose catabolism as influenced by acetate in the presence of insulin. J Biol Chem. 1966 Jun 25;241(12):2862–2869. [PubMed] [Google Scholar]
  25. Flatt J. P. Conversion of carbohydrate to fat in adipose tissue: an energy-yielding and, therefore, self-limiting process. J Lipid Res. 1970 Mar;11(2):131–143. [PubMed] [Google Scholar]
  26. GARLAND P. B., RANDLE P. J. A rapid enzymatic assay for glycerol. Nature. 1962 Dec 8;196:987–988. doi: 10.1038/196987a0. [DOI] [PubMed] [Google Scholar]
  27. HAGEN J. H., BALL E. G. Studies on the metabolism of adipose tissue. IV. The effect of insulin and adrenaline on glucose utilization, lactate production, and net gas exchange. J Biol Chem. 1960 Jun;235:1545–1549. [PubMed] [Google Scholar]
  28. Hall C. L., Ball E. G. Factors affecting lipolysis rates in rat adipose tissue. Biochim Biophys Acta. 1970 Jul 14;210(2):209–220. doi: 10.1016/0005-2760(70)90165-7. [DOI] [PubMed] [Google Scholar]
  29. Halperin M. L., Robinson B. H. The role of the cytoplasmic redox potential in the control of fatty acid synthesis from glucose, pyruvate and lactate in white adipose tissue. Biochem J. 1970 Jan;116(2):235–240. doi: 10.1042/bj1160235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ho R. J., Jeanrenaud B. Insulin-like action of ouabain. I. Effect on carbohydrate metabolism. Biochim Biophys Acta. 1967 Aug 8;144(1):61–73. doi: 10.1016/0005-2760(67)90077-x. [DOI] [PubMed] [Google Scholar]
  31. ITAYA K., UI M. COLORIMETRIC DETERMINATION OF FREE FATTY ACIDS IN BIOLOGICAL FLUIDS. J Lipid Res. 1965 Jan;6:16–20. [PubMed] [Google Scholar]
  32. Jungas R. L. Effect of insulin on fatty acid ynthesis from pyruvate, lactage, or endogenous sources in adipose tissue: evidence for the hormonal regulation of pyruvate dehydrogenase. Endocrinology. 1970 Jun;86(6):1368–1375. doi: 10.1210/endo-86-6-1368. [DOI] [PubMed] [Google Scholar]
  33. Jungas R. L. Fatty acid synthesis in adipose tissue incubated in tritiated water. Biochemistry. 1968 Oct;7(10):3708–3717. doi: 10.1021/bi00850a050. [DOI] [PubMed] [Google Scholar]
  34. Katz J., Landau B. R., Bartsch G. E. The pentose cycle, triose phosphate isomerization, and lipogenesis in rat adipose tissue. J Biol Chem. 1966 Feb 10;241(3):727–740. [PubMed] [Google Scholar]
  35. LARDY H. A., PRESSMAN B. C. Effect of surface active agents on the latent ATPase of mitochondria. Biochim Biophys Acta. 1956 Sep;21(3):458–466. doi: 10.1016/0006-3002(56)90182-2. [DOI] [PubMed] [Google Scholar]
  36. LEBOEUF B., CAHILL G. F., Jr Studies on rat adipose tissue in vitro. VIII. Effect of preparations of pituitary adrenocorticotropic and growth hormones on glucose metabolism. J Biol Chem. 1961 Jan;236:41–46. [PubMed] [Google Scholar]
  37. LEBOEUF B., FLINN R. B., CAHILL G. F., Jr Effect of epinephrine on glucose uptake and glycerol release by adipose tissue in vitro. Proc Soc Exp Biol Med. 1959 Oct-Dec;102:527–529. doi: 10.3181/00379727-102-25306. [DOI] [PubMed] [Google Scholar]
  38. LYNN W. S., MACLEOD R. M., BROWN R. H. Effects of epinephrine, insulin, and corticotrophin on the metabolism of rat adipose tissue. J Biol Chem. 1960 Jul;235:1904–1911. [PubMed] [Google Scholar]
  39. Linn T. C., Pettit F. H., Reed L. J. Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc Natl Acad Sci U S A. 1969 Jan;62(1):234–241. doi: 10.1073/pnas.62.1.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Prusiner S. B., Cannon B., Ching T. M., Lindberg O. Oxidative metabolism in cells isolated from brown adipose tissue. 2. Catecholamine regulated respiratory control. Eur J Biochem. 1968 Dec;7(1):51–57. doi: 10.1111/j.1432-1033.1968.tb19572.x. [DOI] [PubMed] [Google Scholar]
  41. RODBELL M. METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS. J Biol Chem. 1964 Feb;239:375–380. [PubMed] [Google Scholar]
  42. Robinson B. H., Halperin M. L. Transport of reduced nicotinamide-adenine dinucleotide into mitochondria of rat white adipose tissue. Biochem J. 1970 Jan;116(2):229–233. doi: 10.1042/bj1160229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Rognstad R., Katz J. The balance of pyridine nucleotides and ATP in adipose tissue. Proc Natl Acad Sci U S A. 1966 May;55(5):1148–1156. doi: 10.1073/pnas.55.5.1148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rognstad R., Katz J. The effect of 2,4-dinitrophenol on adipose-tissue metabolism. Biochem J. 1969 Feb;111(4):431–444. doi: 10.1042/bj1110431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rubinstein D., Daniel A. M., Lechter L., Beck J. C. Esterification of intra- and extra-cellular free fatty acids by rat adipose tissue. Can J Biochem. 1965 Jun;43(6):635–645. doi: 10.1139/o65-075. [DOI] [PubMed] [Google Scholar]
  46. SHAPIRO B., CHOWERS I., ROSE G. Fatty acid uptake esterification in adipose tissue. Biochim Biophys Acta. 1957 Jan;23(1):115–120. doi: 10.1016/0006-3002(57)90292-5. [DOI] [PubMed] [Google Scholar]
  47. Saggerson E. D., Greenbaum A. L. The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of altered dietary and hormonal conditions. Biochem J. 1970 Sep;119(2):221–242. doi: 10.1042/bj1190221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Saggerson E. D., Greenbaum A. L. The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Biochem J. 1970 Sep;119(2):193–219. doi: 10.1042/bj1190193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Saggerson E. D. The regulation of glyceride synthesis in isolated white-fat cells. The effects of acetate, pyruvate, lactate, palmitate, electron-acceptors, uncoupling agents and oligomycin. Biochem J. 1972 Aug;128(5):1069–1078. doi: 10.1042/bj1281069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Saggerson E. D., Tomassi G. The regulation of glyceride synthesis from pyruvate in isolated fat cells. The effects of palmitate and alteration of dietary status. Eur J Biochem. 1971 Nov 11;23(1):109–117. doi: 10.1111/j.1432-1033.1971.tb01597.x. [DOI] [PubMed] [Google Scholar]
  51. Schimmel R. J., Goodman H. M. Effects of dibutyryl cyclic adenosine 3',5'-monophosphate on glucose transport and metabolism in rat adipose tissue. Biochim Biophys Acta. 1971 Jun 8;239(1):9–15. doi: 10.1016/0005-2760(71)90186-x. [DOI] [PubMed] [Google Scholar]
  52. Schmidt K., Katz J. Metabolism of pyruvate and L-lactate by rat adipose tissue. J Biol Chem. 1969 Apr 25;244(8):2125–2131. [PubMed] [Google Scholar]
  53. Vassalli J. D., Jeanrenaud B. Lipolysis and alpha-aminoisobutyric acid uptake in isolated fat cells. Effects of insulin and lipolytic agents. Biochim Biophys Acta. 1970 May 5;202(3):477–485. doi: 10.1016/0005-2760(70)90118-9. [DOI] [PubMed] [Google Scholar]
  54. WIELAND O. Eine enzymatische Methode zur Bestimmung von Glycerin. Biochem Z. 1957;329(4):313–319. [PubMed] [Google Scholar]
  55. Winand J., Furnelle J., Wodon C., Christophe J. Spectrum of fatty acids synthesized in situ and metabolic heterogeneity of free fatty acids and glycerides within isolated rat adipocytes. Biochim Biophys Acta. 1971 Jul 13;239(2):142–153. doi: 10.1016/0005-2760(71)90160-3. [DOI] [PubMed] [Google Scholar]

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