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J Clin Invest. May 1, 1996; 97(9): 2081–2091.
PMCID: PMC507283

Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet.

Abstract

A new experimental approach was used to determine whether a eucaloric, low fat, high carbohydrate diet increases fatty acid synthesis. Normally volunteers consumed low fat liquid formula diets (10% of calories as fat and 75% as glucose polymers, n = 7) or high fat diets (40% of calories as fat and 45% as glucose polymers, n = 3) for 25 d. The fatty acid composition of each diet was matched to the composition of each subject's adipose tissue and compared with the composition of VLDL triglyceride. By day 10, VLDL triglyceride was markedly enriched in palmitate and deficient in linoleate in all subjects on the low fat diet. Newly synthesized fatty acids accounted for 44 +/- 10% of the VLDL triglyceride. Mass isotopomer distribution analysis of palmitate labeled with intravenously infused 13C-acetate confirmed that increased palmitate synthesis was the likely cause for the accumulation of triglyceride palmitate and "dilution" of linoleate. In contrast, there was minimal fatty acid synthesis on the high diet. Thus, the dietary substitution of carbohydrate for fat stimulated fatty acid synthesis and the plasma accumulation of palmitate-enriched, linoleate-deficient triglyceride. Such changes could have adverse effects on the cardiovascular system.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • HIRSCH J, GOLDRICK RB. SERIAL STUDIES ON THE METABOLISM OF HUMAN ADIPOSE TISSUE. I. LIPOGENESIS AND FREE FATTY ACID UPTAKE AND RELEASE IN SMALL ASPIRATED SAMPLES OF SUBCUTANEOUS FAT. J Clin Invest. 1964 Sep;43:1776–1792. [PMC free article] [PubMed]
  • Sjöström L. Carbohydrate-stimulated fatty acid synthesis de novo in human adipose tissue of different cellular types. Acta Med Scand. 1973 Nov;194(5):387–404. [PubMed]
  • Angel A, Bray GA. Synthesis of fatty acids and cholesterol by liver, adipose tissue and intestinal mucosa from obese and control patients. Eur J Clin Invest. 1979 Oct;9(5):355–362. [PubMed]
  • Barakat HA, McLendon VD, Carpenter JW, Marks RH, Legett N, O'Brien K, Caro JF. Lipogenic potential of liver from morbidly obese patients with and without non-insulin-dependent diabetes. Metabolism. 1991 Mar;40(3):280–285. [PubMed]
  • Goodridge AG. Dietary regulation of gene expression: enzymes involved in carbohydrate and lipid metabolism. Annu Rev Nutr. 1987;7:157–185. [PubMed]
  • Shillabeer G, Hornford J, Forden JM, Wong NC, Lau DC. Hepatic and adipose tissue lipogenic enzyme mRNA levels are suppressed by high fat diets in the rat. J Lipid Res. 1990 Apr;31(4):623–631. [PubMed]
  • Acheson KJ, Schutz Y, Bessard T, Anantharaman K, Flatt JP, Jéquier E. Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am J Clin Nutr. 1988 Aug;48(2):240–247. [PubMed]
  • Hellerstein MK, Christiansen M, Kaempfer S, Kletke C, Wu K, Reid JS, Mulligan K, Hellerstein NS, Shackleton CH. Measurement of de novo hepatic lipogenesis in humans using stable isotopes. J Clin Invest. 1991 May;87(5):1841–1852. [PMC free article] [PubMed]
  • Hellerstein MK, Neese RA. Mass isotopomer distribution analysis: a technique for measuring biosynthesis and turnover of polymers. Am J Physiol. 1992 Nov;263(5 Pt 1):E988–1001. [PubMed]
  • Leitch CA, Jones PJ. Measurement of human lipogenesis using deuterium incorporation. J Lipid Res. 1993 Jan;34(1):157–163. [PubMed]
  • Faix D, Neese R, Kletke C, Wolden S, Cesar D, Coutlangus M, Shackleton CH, Hellerstein MK. Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans. J Lipid Res. 1993 Dec;34(12):2063–2075. [PubMed]
  • Sniderman AD, Cianflone K. Substrate delivery as a determinant of hepatic apoB secretion. Arterioscler Thromb. 1993 May;13(5):629–636. [PubMed]
  • Jayakumar A, Tai MH, Huang WY, al-Feel W, Hsu M, Abu-Elheiga L, Chirala SS, Wakil SJ. Human fatty acid synthase: properties and molecular cloning. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8695–8699. [PMC free article] [PubMed]
  • NIH Consensus conference. Triglyceride, high-density lipoprotein, and coronary heart disease. NIH Consensus Development Panel on Triglyceride, High-Density Lipoprotein, and Coronary Heart Disease. JAMA. 1993 Jan 27;269(4):505–510. [PubMed]
  • Goodnight SH, Jr, Harris WS, Connor WE, Illingworth DR. Polyunsaturated fatty acids, hyperlipidemia, and thrombosis. Arteriosclerosis. 1982 Mar-Apr;2(2):87–113. [PubMed]
  • FOLCH J, LEES M, SLOANE STANLEY GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed]
  • HIRSCH J, FARQUHAR JW, AHRENS EH, Jr, PETERSON ML, STOFFEL W. Studies of adipose tissue in man. A microtechnic for sampling and analysis. Am J Clin Nutr. 1960 Jul-Aug;8:499–511. [PubMed]
  • Ito Y, Hudgins LC, Hirsch J, Shike M. Adipose-tissue fatty acid composition in recipients of long-term total parenteral nutrition (TPN). Am J Clin Nutr. 1991 Jun;53(6):1487–1492. [PubMed]
  • Warnick GR, Benderson J, Albers JJ. Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. Clin Chem. 1982 Jun;28(6):1379–1388. [PubMed]
  • Herbert V, Lau KS, Gottlieb CW, Bleicher SJ. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. [PubMed]
  • Hudgins LC, Hirsch J. Changes in abdominal and gluteal adipose-tissue fatty acid compositions in obese subjects after weight gain and weight loss. Am J Clin Nutr. 1991 Jun;53(6):1372–1377. [PubMed]
  • Phinney SD, Stern JS, Burke KE, Tang AB, Miller G, Holman RT. Human subcutaneous adipose tissue shows site-specific differences in fatty acid composition. Am J Clin Nutr. 1994 Nov;60(5):725–729. [PubMed]
  • BIERMAN EL, PORTE D, Jr, O'HARA DD, SCHWARTZ M, WOOD FC., Jr CHARACTERIZATION OF FAT PARTICLES IN PLASMA OF HYPERLIPEMIC SUBJECTS MAINTAINED ON FAT-FREE HIGH-CARBOHYDRATE DIETS. J Clin Invest. 1965 Feb;44:261–270. [PMC free article] [PubMed]
  • Wene JD, Connor WE, DenBesten L. The development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally. J Clin Invest. 1975 Jul;56(1):127–134. [PMC free article] [PubMed]
  • SWEENEY MJ, ETTELDORF JN, THROOP LJ, TIMMA DL, WRENN EL. Diet and fatty acid distribution in subcutaneous fat and in the cholesterol-triglyceride fraction of serum of young infants. J Clin Invest. 1963 Jan;42:1–9. [PMC free article] [PubMed]
  • Spritz N, Mishkel MA. Effects of dietary fats on plasma lipids and lipoproteins: an hypothesis for the lipid-lowering effect of unsaturated fatty acids. J Clin Invest. 1969 Jan;48(1):78–86. [PMC free article] [PubMed]
  • Baudet MF, Esteva O, Delplanque B, Winchenne N, Jacotot B. Effects of three dietary fats on plasma lipids and lipoproteins in fasting and post-prandial humans after a short-term diet. Lipids. 1980 Apr;15(4):216–223. [PubMed]
  • Clandinin MT, Cheema S, Field CJ, Garg ML, Venkatraman J, Clandinin TR. Dietary fat: exogenous determination of membrane structure and cell function. FASEB J. 1991 Oct;5(13):2761–2769. [PubMed]
  • Clarke SD, Jump DB. Dietary polyunsaturated fatty acid regulation of gene transcription. Annu Rev Nutr. 1994;14:83–98. [PubMed]
  • Siguel EN, Lerman RH. Altered fatty acid metabolism in patients with angiographically documented coronary artery disease. Metabolism. 1994 Aug;43(8):982–993. [PubMed]
  • Riemersma RA, Wood DA, Butler S, Elton RA, Oliver M, Salo M, Nikkari T, Vartiainen E, Puska P, Gey F, et al. Linoleic acid content in adipose tissue and coronary heart disease. Br Med J (Clin Res Ed) 1986 May 31;292(6533):1423–1427. [PMC free article] [PubMed]
  • Wood DA, Riemersma RA, Butler S, Thomson M, Macintyre C, Elton RA, Oliver MF. Linoleic and eicosapentaenoic acids in adipose tissue and platelets and risk of coronary heart disease. Lancet. 1987 Jan 24;1(8526):177–183. [PubMed]
  • Hellerstein MK, Neese RA, Schwarz JM. Model for measuring absolute rates of hepatic de novo lipogenesis and reesterification of free fatty acids. Am J Physiol. 1993 Nov;265(5 Pt 1):E814–E820. [PubMed]
  • Ntambi JM. Dietary regulation of stearoyl-CoA desaturase 1 gene expression in mouse liver. J Biol Chem. 1992 May 25;267(15):10925–10930. [PubMed]
  • Elovson J. Conversions of palmitic and stearic acid in the intact rat. Biochim Biophys Acta. 1965 Oct 4;106(2):291–303. [PubMed]
  • Emken EA, Adlof RO, Rohwedder WK, Gulley RM. Influence of linoleic acid on desaturation and uptake of deuterium-labeled palmitic and stearic acids in humans. Biochim Biophys Acta. 1993 Oct 13;1170(2):173–181. [PubMed]
  • Toorop AI, Romsos DR, Leveille GA. The metabolic fate of dietary 1-[14C]linoleate and 1-[14C]palmitate in meal-fed rats. Proc Soc Exp Biol Med. 1979 Mar;160(3):312–316. [PubMed]
  • Nestel PJ, Barter P. Metabolism of palmitic and linoleic acids in man: differences in turnover and conversion to glycerides. Clin Sci. 1971 Apr;40(4):345–350. [PubMed]
  • Jones PJ, Schoeller DA. Polyunsaturated:saturated ratio of diet fat influences energy substrate utilization in the human. Metabolism. 1988 Feb;37(2):145–151. [PubMed]
  • Moustaïd N, Beyer RS, Sul HS. Identification of an insulin response element in the fatty acid synthase promoter. J Biol Chem. 1994 Feb 25;269(8):5629–5634. [PubMed]
  • Coulston AM, Liu GC, Reaven GM. Plasma glucose, insulin and lipid responses to high-carbohydrate low-fat diets in normal humans. Metabolism. 1983 Jan;32(1):52–56. [PubMed]
  • Smith SC., Jr AHA president's letter. Circulation. 1995 Jul 1;92(1):1–1. [PubMed]
  • Frayn KN, Kingman SM. Dietary sugars and lipid metabolism in humans. Am J Clin Nutr. 1995 Jul;62(1 Suppl):250S–263S. [PubMed]

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