Use of Lipids as Energy Substrates

  • Philip C. CalderEmail author
  • Pierre Singer


Complex lipids and their fatty acid components have important biological activities and are involved in the regulation of many metabolic and physiological processes. Fatty acids are important energy sources and upon complete β-oxidation yield more energy per mole and per carbon atom than glucose. Fatty acid β-oxidation occurs mainly in the mitochondria, and there are specific mechanisms for transporting fatty acids from the cytosol to the mitochondrial matrix to enable their oxidation. Ensuring fatty acid availability for oxidation reduces the need for glucose provision. Fatty acids in foods and in formulas used for nutrition support are esterified into triacylglycerols. There are specific mechanisms for releasing fatty acids from triacylglycerols provided orally and for taking these up into enterocytes. These involve coordinated physical, chemical and enzymatic activities operating from the mouth to the small intestine. In healthy people these processes are very efficient, but they can be disrupted by injury, illness or disease, including critical illness, meaning that fatty acid availability can be decreased in these situations. The products of triacylglycerol digestion and absorption ultimately appear in the bloodstream as triacylglycerols in lipoproteins called chylomicrons. Fatty acids are removed from chylomicrons by the action of lipoprotein lipase, which is promoted by insulin, and can be stored in adipose tissue following their re-esterification into triacylglycerols. In stress states or times of limited glucose availability, fatty acids are released from stored triacylglycerols and appear in the bloodstream as non-esterified fatty acids. These are the substrates for β-oxidation and energy generation. Lipid emulsions used in intravenous nutrition support are metabolised similarly to chylomicrons, but they need to acquire proteins from native lipoproteins to enable this to happen. ESPEN guidelines recommend intravenous lipid infusion in critically ill patients where enteral feeding is not possible. However, excess rates of lipid infusion can lead to hypertriacylglycerolemia and can disrupt organ function, and therefore the rate of lipid infusion needs to be controlled and limited. The critically ill patient displays alterations in lipid metabolism and lipid utilisation that result from insulin resistance, the stress response, inflammation and nutrition support. Fatty acids are the preferred fuel in critical illness, and there is an increase in whole body fat oxidation. However, fatty acid availability may be in excess of needs, and fatty acids not oxidised may be incorporated into triacylglycerols in the liver resulting in hepatic steatosis and hypertriacylglycerolemia, which may be promoted by lipid infusion and by impaired triacylglycerol clearance. Whether these events happen or not is determined by the specific state of the individual critically ill patient. Because the fatty acid components of triacylglycerols are biologically active, the precise composition of lipid used in artificial nutrition support of critically ill patients may affect metabolic, physiological and clinical outcomes.


Cholesteryl Ester Lipoprotein Lipase Nutrition Support Lipid Emulsion Fatty Acid Component 
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  1. 1.
    Abdelhamid YA, Cousins CE, Sim JA, Bellon MS, Nguyen NQ, Horowitz M, Chapman MJ, Deane AM (2015) Effect of critical illness on triglyceride absorption. J Parenter Enteral Nutr 39:966–972CrossRefGoogle Scholar
  2. 2.
    Bonafe L, Berger M, Que YA, Mechanick JJ (2014) Carnitine deficiency in chronic critical illness. Curr Opin Clin Nutr Metab Care 179:200–209CrossRefGoogle Scholar
  3. 3.
    Burdge GC, Calder PC (2015) Introduction to fatty acids and lipids. World Rev Nutr Diet 112:1–16CrossRefPubMedGoogle Scholar
  4. 4.
    Calder PC (2010) Rationale and use of n-3 fatty acids in artificial nutrition. Proc Nutr Soc 69:565–573CrossRefPubMedGoogle Scholar
  5. 5.
    Calder PC (2013) Lipids for intravenous nutrition in hospitalised adult patients: a multiple choice of options. Proc Nutr Soc 72:263–276CrossRefPubMedGoogle Scholar
  6. 6.
    Calder PC (2015) Functional roles of fatty acids and their effects on human health. J Parenter Enteral Nutr 39:18S–32SCrossRefGoogle Scholar
  7. 7.
    Calder PC (2016) Fatty acids: metabolism. In: Caballero B, Finglas P, Toldrá F (eds) The encyclopedia of food and health, vol 2. Academic, Oxford, pp 632–644CrossRefGoogle Scholar
  8. 8.
    Calder PC, Deckelbaum RJ (2013) Intravenous fish oil in hospitalized adult patients: reviewing the reviews. Curr Opin Clin Nutr Metab Care 16:119–123CrossRefPubMedGoogle Scholar
  9. 9.
    Calder PC, Jensen GL, Koletzko BV, Singer P, Wanten GJ (2010) Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions. Intensive Care Med 36:735–749CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Caresta E, Pierro A, Chowdhury M, Peters MJ, Piastra M, Eaton S (2007) Oxidation of intravenous lipid in infants and children with systemic inflammatory response syndrome and sepsis. Pediatr Res 61:228–232CrossRefPubMedGoogle Scholar
  11. 11.
    Carpentier YA, Scruel O (2002) Changes in the concentration and composition of plasma lipoproteins during the acute phase response. Curr Opin Clin Nutr Metab Care 5:153–158CrossRefPubMedGoogle Scholar
  12. 12.
    Chien JY, Jih-Shuin J, Chong-Jen Y, Pan-Chyr Y (2005) Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis. Crit Care Med 33:1688–1693CrossRefPubMedGoogle Scholar
  13. 13.
    de Luca C, Olefsky JM (2006) Stressed out about obesity and insulin resistance. Nat Med 12:41–42CrossRefPubMedGoogle Scholar
  14. 14.
    Druml W, Fischer M, Ratheiser K (1998) Use of intravenous lipids in critically ill patients with sepsis without and with hepatic failure. J Parenter Enteral Nutr 22:217–223CrossRefGoogle Scholar
  15. 15.
    Frayn KN (2010) Metabolic regulation: a human perspective. Wiley-Blackwell, ChichesterGoogle Scholar
  16. 16.
    Green P, Theilla M, Singer P (2016) Lipid metabolism in critical illness. Curr Opin Clin Nutr Metab Care 19:111–115Google Scholar
  17. 17.
    Hill AG, Hill GL (1998) Metabolic response to severe injury. Br J Surg 85:884–890CrossRefPubMedGoogle Scholar
  18. 18.
    Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91CrossRefPubMedGoogle Scholar
  19. 19.
    Hultin M, Mullertz A, Zundel MA, Olivecronna G, Hansen TT, Deckelbaum RJ, Carpentier YA, Olivecronna T (1994) Metabolism of emulsions containing medium- and long-chain triglycerides or interesterified triglycerides. J Lipid Res 35:1850–1860PubMedGoogle Scholar
  20. 20.
    Jones AE, Stolinski M, Smith RD, Murphy JL, Wootton SA (1999) Effect of fatty acid chain length and saturation on the gastrointestinal handling and metabolic disposal of dietary fatty acids in women. Br J Nutr 81:37–43CrossRefPubMedGoogle Scholar
  21. 21.
    Jones PJ, Pencharz PB, Clandinin MT (1985) Whole body oxidation of dietary fatty acids: implications for energy utilization. Am J Clin Nutr 42:769–777PubMedGoogle Scholar
  22. 22.
    Lekkou A, Mouzaki A, Siagris D, Ravani I, Gogos CA (2014) Serum lipid profile, cytokine production, and clinical outcome in patients with severe sepsis. J Crit Care 29:723–727CrossRefPubMedGoogle Scholar
  23. 23.
    Murphy JL, Jones A, Brookes S, Wootton SA (1995) The gastrointestinal handling and metabolism of [1-13C]palmitic acid in healthy women. Lipids 30:291–298CrossRefPubMedGoogle Scholar
  24. 24.
    Murphy JL, Laiho KM, Jones AE, Wootton SA (1998) Metabolic handling of 13C labelled tripalmitin in healthy controls and patients with cystic fibrosis. Arch Dis Child 79:44–47CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219–246CrossRefPubMedGoogle Scholar
  26. 26.
    Richelle M, Deckelbaum RJ, Vanweyenberg V, Carpentier YA (1997) Lipoprotein metabolism during and after a 6-h infusion of MCT/LCT vs LCT emulsion in man. Clin Nutr 16:119–123CrossRefPubMedGoogle Scholar
  27. 27.
    Simoens C, Deckelbaum RJ, Carpentier YA (2004) Metabolism of defined structured triglyceride particles compared to mixtures of medium and long chain triglycerides intravenously infused in dogs. Clin Nutr 23:665–672CrossRefPubMedGoogle Scholar
  28. 28.
    Simoens CM, Deckelbaum RJ, Massaut JJ, Carpentier YA (2008) Inclusion of 10% fish oil in mixed medium-chain triacylglycerol-long-chain triacylglycerol emulsions increases plasma triacylglycerol clearance and induces rapid eicosapentaenoic acid (20:5n-3) incorporation into blood cell phospholipids. Am J Clin Nutr 88:282–288PubMedGoogle Scholar
  29. 29.
    Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, Griffiths R, Kreyman G, Leverve X, Pichard C (2009) ESPEN guidelines on parenteral nutrition: intensive care. Clin Nutr 28:387–400CrossRefPubMedGoogle Scholar
  30. 30.
    Tappy L, Chiolero R (2007) Substrate utilization in sepsis and multiple organ failure. Crit Care Med 35:S531–S534CrossRefPubMedGoogle Scholar
  31. 31.
    Tappy L, Schwarz J-M, Schneiter P, Cayeux C, Revelly J-P, Fagerquist C, Jequier E, Chiolero R (1998) Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients. Crit Care Med 26:860–867CrossRefPubMedGoogle Scholar
  32. 32.
    Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Human Development and Health Academic Unit, Faculty of MedicineUniversity of SouthamptonSouthamptonUK
  2. 2.NIHR Southampton Biomedical Research CentreUniversity Hospital Southampton NHS Foundation Trust and University of SouthamptonSouthamptonUK
  3. 3.Institute for Nutrition Research, Rabin Medical Center, Beilinson HospitalPetah TikvaIsrael

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