Horm Metab Res 2011; 43(11): 754-759
DOI: 10.1055/s-0031-1287854
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Metabolic Alterations in Adipose Tissue During the Early Phase of Experimental Endotoxemia in Humans

P. Wellhoener
1   University Hospital Schleswig Holstein, Campus Luebeck, Department of Internal Medicine I, Luebeck, Germany
,
A. Vietheer
1   University Hospital Schleswig Holstein, Campus Luebeck, Department of Internal Medicine I, Luebeck, Germany
,
F. Sayk
1   University Hospital Schleswig Holstein, Campus Luebeck, Department of Internal Medicine I, Luebeck, Germany
,
B. Schaaf
1   University Hospital Schleswig Holstein, Campus Luebeck, Department of Internal Medicine I, Luebeck, Germany
,
H. Lehnert
1   University Hospital Schleswig Holstein, Campus Luebeck, Department of Internal Medicine I, Luebeck, Germany
,
C. Dodt
2   Klinikum Bogenhausen, Department of Accident and Emergency, Munich, Germany
› Author Affiliations
Further Information

Publication History

received 28 May 2011

accepted 06 September 2011

Publication Date:
18 October 2011 (online)

Abstract

Adipose tissue plays an important role in energy homeostasis; however, there is only little knowledge about its metabolic activity during critical illness or sepsis. We assessed adipose tissue metabolic activity and local blood flow during experimental endotoxemia in otherwise healthy humans. In a prospective, placebo controlled and randomized experiment we measured changes in lactate, glycerol, and pyruvate concentrations in microdialysate samples of femoral adipose tissue after an intravenous bolus of lipopolysaccharide (LPS, 4 ng/kg). Intravenous endotoxin caused an early and constant increase in interstitial pyruvate, while formation of lactate in adipose tissue was not affected. In contrast, lactate levels in serum were elevated significantly after 90 min (p<0.05) and likewise, serum glycerol concentrations rose 90 min after LPS treatment (p<0.05) and 60 min earlier than in adipose tissue. Subcutaneous adipose tissue blood perfusion increased 2-fold while there was a strong decline in skin blood flow. Pyruvate accumulation in subcutaneous adipose tissue is an early marker of endotoxemia. While adipose tissue is a major source of serum glycerol and lactate in humans during physiological conditions, it contributes only little to increased serum lactate and glycerol levels during endotoxemia.

 
  • References

  • 1 Hudgins LC, Parker TS, Levine DM, Gordon BR, Saal SD, Jiang XC, Seidman CE, Tremaroli JD, Lai J, Rubin AL. A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers. J Lipid Res 2003; 44: 1489-1498
  • 2 Suffredini AF, Harpel PC, Parrillo JE. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. N Engl J Med 1989; 320: 1165-1172
  • 3 Streat SJ, Beddoe AH, Hill GL. Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. J Trauma 1987; 27: 262-266
  • 4 Cooney RN, Kimball SR, Vary TC. Regulation of skeletal muscle protein turnover during sepsis: mechanisms and mediators. Shock 1997; 7: 1-16
  • 5 Michie HR, Manogue KR, Spriggs DR, Revhaug A, O’Dwyer S, Dinarello CA, Cerami A, Wolff SM, Wilmore DW. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 1988; 318: 1481-1486
  • 6 Martich GD, Boujoukos AJ, Suffredini AF. Response of man to endotoxin. Immunobiology 1993; 187: 403-416
  • 7 Enoksson S, Nordenstrom J, Bolinder J, Arner P. Influence of local blood flow on glycerol levels in human adipose tissue. Int J Obes Relat Metab Disord 1995; 19: 350-354
  • 8 Dodt C, Lonnroth P, Fehm HL, Elam M. Intraneural stimulation elicits an increase in subcutaneous interstitial glycerol levels in humans. J Physiol (Lond) 1999; 521 (Pt 2) 545-552
  • 9 Hagstrom-Toft E, Enoksson S, Moberg E, Bolinder J, Arner P. Absolute concentrations of glycerol and lactate in human skeletal muscle, adipose tissue, and blood. Am J Physiol 1997; 273: E584-E592
  • 10 Lonnroth P. Microdialysis in adipose tissue and skeletal muscle. Horm Metab Res 1997; 29: 344-346
  • 11 De Boer J, Korf J, Plijter-Groendijk H. In vivo monitoring of lactate and glucose with microdialysis and enzyme reactors in intensive care medicine. Int J Artif Organs 1994; 17: 163-170
  • 12 Poling J, Leptien A, Klaus S, Rees W, Kraatz E, Wiebe K, Bahlmann L. Analysis of the myocardial metabolism by microdialysis during open beating heart surgery. Scand Cardiovasc J 2007; 41: 114-119
  • 13 Wellhoener P, Rolle D, Lonnroth P, Strindberg L, Elam M, Dodt C. Laser Doppler Flowmetry reveals rapid perfusion changes in adipose tissue of lean and obese females. Am J Physiol Endocrinol Metab 2006; 291: E1025-E1030
  • 14 Albert J, Radomski A, Soop A, Sollevi A, Frostell C, Radomski MW. Differential release of matrix metalloproteinase-9 and nitric oxide following infusion of endotoxin to human volunteers. Acta Anaesthesiol Scand 2003; 47: 407-410
  • 15 Fong Y, Matthews DE, He W, Marano MA, Moldawer LL, Lowry SF. Whole body and splanchnic leucine, phenylalanine, and glucose kinetics during endotoxemia in humans. Am J Physiol 1994; 266: R419-R425
  • 16 Godin PJ, Fleisher LA, Eidsath A, Vandivier RW, Preas HL, Banks SM, Buchman TG, Suffredini AF. Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized, crossover trial. Crit Care Med 1996; 24: 1117-1124
  • 17 Landman RE, Puder JJ, Xiao E, Freda PU, Ferin M, Wardlaw SL. Endotoxin stimulates leptin in the human and nonhuman primate. J Clin Endocrinol Metab 2003; 88: 1285-1291
  • 18 Nanni G, Siegel JH, Coleman B, Fader P, Castiglione R. Increased lipid fuel dependence in the critically ill septic patient. J Trauma 1984; 24: 14-30
  • 19 Shaw JH, Wolfe RR. Energy and protein metabolism in sepsis and trauma. Aust NZ J Surg 1987; 57: 41-47
  • 20 Stoner HB, Little RA, Frayn KN, Elebute AE, Tresadern J, Gross E. The effect of sepsis on the oxidation of carbohydrate and fat. Br J Surg 1983; 70: 32-35
  • 21 Arner P, Bolinder J, Eliasson A, Lundin A, Ungerstedt U. Microdialysis of adipose tissue and blood for in vivo lipolysis studies. Am J Physiol 1988; 255: E737-E742
  • 22 Dodt C, Lonnroth P, Fehm HL, Elam M. The subcutaneous lipolytic response to regional neural stimulation is reduced in obese women. Diabetes 2000; 49: 1875-1879
  • 23 Fellander G, Nordenstrom J, Tjader I, Bolinder J, Arner P. Lipolysis during abdominal surgery. J Clin Endocrinol Metab 1994; 78: 150-155
  • 24 Krogh-Madsen R, Plomgaard P, Akerstrom T, Moller K, Schmitz O, Pedersen BK. Effect of short-term intralipid infusion on the immune response during low-dose endotoxemia in humans. Am J Physiol Endocrinol Metab 2008; 294: E371-E379
  • 25 Spitzer JJ, Bagby GJ, Meszaros K, Lang CH. Alterations in lipid and carbohydrate metabolism in sepsis. JPEN J Parenter Enteral Nutr. 1988; 12: 53S-58S
  • 26 Stouthard JM, Romijn JA, van der PT, Endert E, Klein S, Bakker PJ, Veenhof CH, Sauerwein HP. Endocrinologic and metabolic effects of interleukin-6 in humans. Am J Physiol 1995; 268: E813-E819
  • 27 Sugawara K, Miyata G, Shineha R, Satomi S. The lipolytic responsiveness to endotoxin in subcutaneous adipose tissue is greater than mesenteric adipose tissue. Tohoku J Exp Med 2003; 199: 171-179
  • 28 Navegantes LC, Sjostrand M, Gudbjornsdottir S, Strindberg L, Elam M, Lonnroth P. Regulation and counterregulation of lipolysis in vivo: different roles of sympathetic activation and insulin. J Clin Endocrinol Metab 2003; 88: 5515-5520
  • 29 Jansson PA, Smith U, Lonnroth P. Evidence for lactate production by human adipose tissue in vivo. Diabetologia 1990; 33: 253-256
  • 30 Gore DC, Jahoor F, Hibbert JM, DeMaria EJ. Lactic acidosis during sepsis is related to increased pyruvate production, not deficits in tissue oxygen availability. Ann Surg 1996; 224: 97-102
  • 31 Wolfe RR, Jahoor F, Herndorn DO, Miyoshi H. Isotopic evaluation of the metabolism of pyruvate and related substrates in normal adult volunteers and severely burned children: effect of dichloroacetate and glucose infusion. Surgery 1991; 110: 54-66
  • 32 Das UN. Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. Med Sci Monit 2006; 12: RA79-RA84
  • 33 Ulloa L, Ochani M, Yang H, Tanovic M, Halperin D, Yang R, Czura CJ, Fink MP, Tracey KJ. Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci USA 2002; 99: 12351-12356
  • 34 Rosdahl H, Hamrin K, Ungerstedt U, Henriksson J. Metabolite levels in human skeletal muscle and adipose tissue studied with microdialysis at low perfusion flow. Am J Physiol 1998; 274: E936-E945
  • 35 Jansson PA, Larsson A, Smith U, Lonnroth P. Lactate release from the subcutaneous tissue in lean and obese men. J Clin Invest 1994; 93: 240-246
  • 36 Ellmerer M, Schaupp L, Sendlhofer G, Wutte A, Brunner GA, Trajanoski Z, Skrabal F, Wach P, Pieber TR. Lactate metabolism of subcutaneous adipose tissue studied by open flow microperfusion. J Clin Endocrinol Metab 1998; 83: 4394-4401
  • 37 Dimopoulou I, Nikitas N, Orfanos SE, Theodorakopoulou M, Vassiliadi D, Ilias I, Ikonomidis I, Boutati E, Maratou E, Tsangaris I, Karkouli G, Tsafou E, Diamantakis A, Kopterides P, Maniatis N, Kotanidou A, Armaganidis A, Ungerstedt U. Kinetics of adipose tissue microdialysis-derived metabolites in critically ill septic patients: associations with sepsis severity and clinical outcome. Shock 2011; 35: 343-348
  • 38 Martinez A, Chiolero R, Bollman M, Revelly JP, Berger M, Cayeux C, Tappy L. Assessment of adipose tissue metabolism by means of subcutaneous microdialysis in patients with sepsis or circulatory failure. Clin Physiol Funct Imaging 2003; 23: 286-292
  • 39 Klaus S, Staubach KH, Heringlake M, Gliemroth J, Schmucker P, Bahlmann L. Tissue metabolism during endotoxin shock after pretreatment with monophosphoryl lipid A. Cardiovasc Res 2003; 59: 105-112
  • 40 Vary TC, O’Neill P, Cooney RN, Maish III G, Shumate M. Chronic infusion of interleukin 1 induces hyperlactatemia and altered regulation of lactate metabolism in skeletal muscle. JPEN J Parenter Enteral Nutr 1999; 23: 213-217
  • 41 Levy B, Desebbe O, Montemont C, Gibot S. Increased aerobic glycolysis through beta-2 stimulation is a common mechanism involved in lactate formation during shock states. Shock 2008; 30: 417-421