Download PDF
Horm Metab Res 2013; 45(05): 378-382
DOI: 10.1055/s-0032-1330015
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Prolonged Fasting and the Effects on Biomarkers of Inflammation and on Adipokines in Healthy Lean Men

N. A. van Herpen
1   Department of Human Biology, NUTRIM – School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
2   TI Food and Nutrition, Wageningen, The Netherlands
,
H. Sell
3   Paul Langerhans Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany
,
J. Eckel
3   Paul Langerhans Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany
,
P. Schrauwen
1   Department of Human Biology, NUTRIM – School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
2   TI Food and Nutrition, Wageningen, The Netherlands
,
R. P. Mensink
1   Department of Human Biology, NUTRIM – School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
2   TI Food and Nutrition, Wageningen, The Netherlands
› Author Affiliations
Further Information

Publication History

received 13 July 2012

accepted 25 October 2012

Publication Date:
12 December 2012 (online)

Also available at
    Permissions and Reprints

Abstract

Obesity and insulin resistance are associated with low-grade systemic inflammation, which is related to increased concentrations of plasma FFAs, glucose, or insulin. Prolonged fasting induces insulin resistance due to elevated plasma FFAs, but is not accompanied by hyperinsulinemia or hyperglycemia. This makes it possible to study effects of physiologically increased FFA concentrations on inflammatory markers, when insulin and glucose concentrations are not increased. In random order, 10 healthy young lean men (mean BMI: 22.8 kg/m2) were fasted or fed in energy balance for 60 h with a 2-week wash-out period. Subjects stayed in a respiration chamber during the 60-h periods. Blood samples were taken after 12, 36, and 60 h. Then, a hyperinsulinemic-euglycemic clamp was performed.

Fasting decreased insulin sensitivity by 45% and increased FFA concentrations 5-fold. Fasting did not change concentrations of the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-8, or of hs-CRP. Effects on vascular endothelial growth factor (VEGF) – which may positively relate to insulin resistance, and on chemerin and leptin – adipokines related to obesity, and obesity-related pathologies, were also studied. At t=60 h, VEGF concentrations were significantly increased during the fasted period (p<0.05). At the same time point, chemerin (p<0.01) and leptin (p<0.01) were significantly decreased after fasting. For leptin, this decrease was also significant after 36 h (p<0.01). Adiponectin levels remained unchanged. In healthy young lean men, fasting-induced increases in FFAs leading to insulin resistance do not cause changes in concentrations of the inflammatory cytokines. VEGF concentrations increased and those of chemerin decreased.

Key words

free fatty acids - cytokines - adipokines
 

  • References

  • 1 Tripathy D, Mohanty P, Dhindsa S, Syed T, Ghanim H, Aljada A, Dandona P. Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes 2003; 52: 2882-2887
    CrossrefPubMedGoogle Scholar
  • 2 Ford ES, Ajani UA, Mokdad AH. The metabolic syndrome and concentrations of C reactive protein among U.S. youth. Diabetes Care 2005; 28: 878-881
    CrossrefPubMedGoogle Scholar
  • 3 Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001; 285: 2481-2485
    CrossrefPubMedGoogle Scholar
  • 4 Frohlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H, Muche R, Brenner H, Koenig W. Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care 2000; 23: 1835-1839
    CrossrefPubMedGoogle Scholar
  • 5 Abbasi F, Chu JW, Lamendola C, McLaughlin T, Hayden J, Reaven GM, Reaven PD. Discrimination between obesity and insulin resistance in the relationship with adiponectin. Diabetes 2004; 53: 585-590
    CrossrefPubMedGoogle Scholar
  • 6 McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P, Reaven P. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation 2002; 106: 2908-2912
    CrossrefPubMedGoogle Scholar
  • 7 Saad MF, Khan A, Sharma A, Michael R, Riad-Gabriel MG, Boyadjian R, Jinagouda SD, Steil GM, Kamdar V. Physiological insulinemia acutely modulates plasma leptin. Diabetes 1998; 47: 544-549
    CrossrefPubMedGoogle Scholar
  • 8 Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M, Olefsky JM. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 2002; 51: 2968-2974
    CrossrefPubMedGoogle Scholar
  • 9 Schwartz EA, Reaven PD. Molecular and signaling mechanisms of atherosclerosis in insulin resistance. Endocrinol Metab Clin North Am 2006; 35: 525-549 viii
    CrossrefPubMedGoogle Scholar
  • 10 Hoeks J, van Herpen NA, Mensink M, Moonen-Kornips E, van Beurden D, Hesselink MK, Schrauwen P. Prolonged fasting identifies skeletal muscle mitochondrial dysfunction as consequence rather than cause of human insulin resistance. Diabetes 2010; 59: 2117-2125
    CrossrefPubMedGoogle Scholar
  • 11 Sandhofer A, Tatarczyk T, Kirchmair R, Iglseder B, Paulweber B, Patsch JR, Schratzberger P. Are plasma VEGF and its soluble receptor sFlt-1 atherogenic risk factors? Cross-sectional data from the SAPHIR study. Atherosclerosis 2009; 206: 265-269
    CrossrefPubMedGoogle Scholar
  • 12 Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, Walder K, Segal D. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007; 148: 4687-4694
    CrossrefPubMedGoogle Scholar
  • 13 Parlee SD, Ernst MC, Muruganandan S, Sinal CJ, Goralski KB. Serum chemerin levels vary with time of day and are modified by obesity and tumor necrosis factor-{alpha}. Endocrinology 2010; 151: 2590-2602
    CrossrefPubMedGoogle Scholar
  • 14 Schrauwen P, van Marken Lichtenbelt WD, Westerterp KR. Energy balance in a respiration chamber: individual adjustment of energy intake to energy expenditure. Int J Obes Relat Metab Disord 1997; 21: 769-774
    CrossrefPubMedGoogle Scholar
  • 15 Schoffelen PF, Westerterp KR, Saris WH, Ten Hoor F. A dual-respiration chamber system with automated calibration. J Appl Physiol 1997; 83: 2064-2072
    PubMedGoogle Scholar
  • 16 Schrauwen P, van Marken Lichtenbelt WD, Saris WH, Westerterp KR. Changes in fat oxidation in response to a high-fat diet. Am J Clin Nutr 1997; 66: 276-282
    PubMedGoogle Scholar
  • 17 van der Crabben SN, Allick G, Ackermans MT, Endert E, Romijn JA, Sauerwein HP. Prolonged fasting induces peripheral insulin resistance, which is not ameliorated by high dose salicylate. J Clin Endocrinol Metab 2008; 93: 638-641
    CrossrefPubMedGoogle Scholar
  • 18 Pickup JC, Crook MA. Is Type II diabetes mellitus a disease of the innate immune system?. Diabetologia 1998; 41: 1241-1248
    CrossrefPubMedGoogle Scholar
  • 19 Stegenga ME, van der Crabben SN, Dessing MC, Pater JM, Van Den Pangaart PS, De Vos AF, Tanck MW, Roos D, Sauerwein HP, Van Der Poll T. Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans. Diabetic Medicine 2008; 25: 157-164
    CrossrefPubMedGoogle Scholar
  • 20 Loebig M, Klement J, Schmoller A, Betz S, Heuck N, Schweiger U, Peters A, Schultes B, Oltmanns KM. Evidence for a relationship between VEGF and BMI independent of insulin sensitivity by glucose clamp procedure in a homogenous group healthy young men. PLoS One 2010; 5: e12610
    CrossrefPubMedGoogle Scholar
  • 21 Dandona P, Aljada A, Mohanty P, Ghanim H, Bandyopadhyay A, Chaudhuri A. Insulin suppresses plasma concentration of vascular endothelial growth factor and matrix metalloproteinase-9. Diabetes Care 2003; 26: 3310-3314
    CrossrefPubMedGoogle Scholar
  • 22 Sone H, Kawakami Y, Okuda Y, Kondo S, Hanatani M, Suzuki H, Yamashita K. Vascular endothelial growth factor is induced by long-term high glucose concentration and up regulated by acute glucose deprivation in cultured bovine retinal pigmented epithelial cells. Biochem Biophys Res Commun 1996; 221: 193-198
    CrossrefPubMedGoogle Scholar
  • 23 Merl V, Peters A, Oltmanns KM, Kern W, Hubold C, Fehm HL, Born J, Schultes B. Antecedent hypoglycaemia attenuates vascular endothelial growth factor response to subsequent hypoglycaemia in healthy men. Diabet Med 2005; 22: 1278-1281
    CrossrefPubMedGoogle Scholar
  • 24 Dantz D, Bewersdorf J, Fruehwald-Schultes B, Kern W, Jelkmann W, Born J, Fehm HL, Peters A. Vascular endothelial growth factor: a novel endocrine defensive response to hypoglycemia. J Clin Endocrinol Metab 2002; 87: 835-840
    CrossrefPubMedGoogle Scholar
  • 25 Boden G. Pathogenesis of type 2 diabetes. Insulin resistance. Endocrinol Metab Clin North Am 2001; 30: 801-815 v
    CrossrefPubMedGoogle Scholar
  • 26 Lamers D, Schlich R, Greulich S, Sasson S, Sell H, Eckel J. Oleic acid and adipokines synergize in inducing proliferation and inflammatory signaling in human vascular smooth muscle cells. J Cell Mol Med 2011; 15: 1177-1188
    CrossrefPubMedGoogle Scholar
  • 27 Sell H, Laurencikiene J, Taube A, Eckardt K, Cramer A, Horrighs A, Arner P, Eckel J. Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells. Diabetes 2009; 58: 2731-2740
    CrossrefPubMedGoogle Scholar
  • 28 Kralisch S, Weise S, Sommer G, Lipfert J, Lossner U, Bluher M, Stumvoll M, Fasshauer M. Interleukin-1beta induces the novel adipokine chemerin in adipocytes in vitro. Regul Pept 2009; 154: 102-106
    CrossrefPubMedGoogle Scholar
  • 29 Tan BK, Chen J, Farhatullah S, Adya R, Kaur J, Heutling D, Lewandowski KC, O’Hare JP, Lehnert H, Randeva HS. Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes 2009; 58: 1971-1977
    CrossrefPubMedGoogle Scholar
  • 30 Weigert J, Neumeier M, Wanninger J, Bauer S, Farkas S, Scherer MN, Schnitzbauer A, Schaffler A, Aslanidis C, Scholmerich J, Buechler C. Serum galectin-3 is elevated in obesity and negatively correlates with glycosylated hemoglobin in type 2 diabetes. J Clin Endocrinol Metab 2010; 95: 1404-1411
    CrossrefPubMedGoogle Scholar
  • 31 Merl V, Peters A, Oltmanns KM, Kern W, Born J, Fehm HL, Schultes B. Serum adiponectin concentrations during a 72-h fast in over- and normal-weight humans. Int J Obes (Lond) 2005; 29: 998-1001
    CrossrefPubMedGoogle Scholar
  • 32 Gavrila A, Chan JL, Yiannakouris N, Kontogianni M, Miller LC, Orlova C, Mantzoros CS. Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross sectional and interventional studies. J Clin Endocrinol Metab 2003; 88: 4823-4831
    CrossrefPubMedGoogle Scholar