Exp Clin Endocrinol Diabetes 2015; 123(09): 553-560
DOI: 10.1055/s-0035-1555942
Article
© Georg Thieme Verlag KG Stuttgart · New York

Short-term Regulation of Resistin in vivo by Oral Lipid Ingestion and in vitro by Fatty Acid Stimulation

A. Schmid
1   Department of Internal Medicine III, Giessen University Hospital, Germany
,
S. Leszczak
2   Department of Internal Medicine I, Regensburg University Hospital, Germany
,
I. Ober
2   Department of Internal Medicine I, Regensburg University Hospital, Germany
,
T. Karrasch
1   Department of Internal Medicine III, Giessen University Hospital, Germany
,
A. Schäffler
1   Department of Internal Medicine III, Giessen University Hospital, Germany
› Author Affiliations
Further Information

Publication History

received 24 March 2015
first decision 24 June 2015

accepted 10 July 2015

Publication Date:
18 August 2015 (online)

Abstract

Background and aim: Dysbalance of pro- and anti-inflammatory adipokines is a hallmark of metabolic syndrome but their nutrition-dependent regulation in healthy individuals is poorly characterized. We investigated pro-inflammatory resistin and anti-inflammatory adiponectin regulation during oral lipid ingestion (OLI) in healthy adults. Response of resistin upon free fatty acid (FFA) stimulation was investigated in 3T3-L1 adipocytes.

Material and methods: 100 healthy volunteers underwent OLI. Venous blood was drawn after 0, 2, 4, and 6 hours (h). Subjects were characterized by anthropometric and standard laboratory parameters. Serum concentrations of adiponectin and resistin were measured by enzyme-linked immunosorbent assay (ELISA). Adipocytes were stimulated with FFA and concentrations of adipokines were measured by ELISA.

Results: Irrespective of BMI and gender, OLI led to a significant reduction of resistin serum levels in a stepwise manner whereas adiponectin concentrations remained unchanged. There were positive correlations of resistin with waist/hip ratio and visfatin levels, as was calculated by regression analysis. Resistin concentrations were significantly higher in smokers when compared to non-smokers. Adiponectin concentrations were higher in females and in users of hormonal contraception. Adiponectin levels showed a positive correlation with heart rate and HDL cholesterol and a negative correlation with age, waist/hip-ratio, BMI, diastolic/systolic blood pressure, visfatin levels and LDL/HDL-ratio. Resistin secretion was significantly induced by palmitic acid, linoleic acid and oleic acid in adipocytes.

Conclusions: OLI is a physiological repressor of systemic resistin release whereas FFA upregulate resistin release in vitro from adipocytes.

 
  • References

  • 1 Lehrke M, Lazar MA. Inflamed about obesity. Nature medicine 2004; 10: 126-127
  • 2 Clement K, Langin D. Regulation of inflammation-related genes in human adipose tissue. J Intern Med 2007; 262: 422-430
  • 3 Ferrante Jr AW. Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med 2007; 262: 408-414
  • 4 Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med 2008; 14: 222-231
  • 5 Weisberg SP, McCann D, Desai M et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796-1808
  • 6 Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 2008; 93: S64-S73
  • 7 Ito A, Suganami T, Yamauchi A et al. Role of CC chemokine receptor 2 in bone marrow cells in the recruitment of macrophages into obese adipose tissue. J Biol Chem 2008; 283: 35715-35723
  • 8 Jernas M, Palming J, Sjoholm K et al. 2006; Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression. FASEB J 2006; 20: 1540-1542
  • 9 Vettor R, Milan G, Rossato M et al. Review article: adipocytokines and insulin resistance. Aliment Pharmacol Ther 2005; 22 (Suppl. 02) 3-10
  • 10 Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obes 2013; 2013: 393192
  • 11 Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin – the classical, resistin – the controversial, adiponectin – the promising, and more to come. Best Pract Res Clin Endocrinol Metab 2005; 19: 525-546
  • 12 Flehmig G, Scholz M, Kloting N et al. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation. PloS one 2014; 9: e99785
  • 13 Mantzoros CS, Magkos F, Brinkoetter M et al. Leptin in human physiology and pathophysiology. American journal of physiology. Endocrinology and metabolism 2011; 301: E567-E584
  • 14 Lee S, Kwak HB. Role of adiponectin in metabolic and cardiovascular disease. Journal of exercise rehabilitation 2014; 10: 54-59
  • 15 Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer 2006; 94: 1221-1225
  • 16 Matsuzawa Y. Adipocytokines: emerging therapeutic targets. Curr Atheroscler Rep 2005; 7: 58-62
  • 17 Steppan CM, Brown EJ, Wright CM et al. A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci USA 2001; 98: 502-506
  • 18 Steppan CM, Lazar MA. The current biology of resistin. J Intern Med 2004; 255: 439-447
  • 19 Steppan CM, Bailey ST, Bhat S et al. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307-312
  • 20 Curat CA, Wegner V, Sengenes C et al. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 2006; 49: 744-747
  • 21 Bokarewa M, Nagaev I, Dahlberg L et al. an adipokine with potent proinflammatory properties. J Immunol 2005; 174: 5789-5795
  • 22 Kawanami D, Maemura K, Takeda N et al. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun 2004; 314: 415-419
  • 23 Karrasch T, Leszczak S, Bala M et al. Short-term regulation of Visfatin release in vivo by oral lipid ingestion and in vitro by fatty acid stimulation. Experimental and clinical endocrinology & diabetes: official journal, German Society of Endocrinology [and] German Diabetes Association 2014; 122: 126-134
  • 24 Green H, Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 1975; 5: 19-27
  • 25 Zaitsu H, Serrero G. Pedersen fetuin contains three adipogenic factors with distinct biochemical characteristics. J Cell Physiol 1990; 144: 485-491
  • 26 Bachmeier M, Loffler G. Adipogenic activities in commercial preparations of fetuin. Horm Metab Res 1994; 26: 92-96
  • 27 Green H, Kehinde O. Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. J Cell Physiol 1979; 101: 169-171
  • 28 Green H, Meuth M. An established pre-adipose cell line and its differentiation in culture. Cell 1974; 3: 127-133
  • 29 Cornelius P, MacDougald OA, Lane MD. Regulation of adipocyte development. Annu Rev Nutr 1994; 14: 99-129
  • 30 MacDougald OA, Lane MD. Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem 1995; 64: 345-373
  • 31 Schaeffler A, Gross P, Buettner R et al. Fatty acid-induced induction of Toll-like receptor-4/nuclear factor-kappaB pathway in adipocytes links nutritional signalling with innate immunity. Immunology 2009; 126: 233-245
  • 32 Kopp A, Gross P, Falk W et al. Fatty acids as metabolic mediators in innate immunity. Eur J Clin Invest 2009;
  • 33 Musso G, Gambino R, Pacini G et al. Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver. The American journal of clinical nutrition 2009; 89: 558-567
  • 34 Thomsen C, Rasmussen O, Lousen T et al. Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects. The American journal of clinical nutrition 1999; 69: 1135-1143
  • 35 Westerink J, Hajer GR, Kranendonk ME et al. An oral mixed fat load is followed by a modest anti-inflammatory adipocytokine response in overweight patients with metabolic syndrome. Lipids 2014; 49: 247-254
  • 36 Musso G, Cassader M, De Michieli F et al. Nonalcoholic steatohepatitis versus steatosis: adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism. Hepatology 2012; 56: 933-942
  • 37 Signori LU, Vargas da Silva AM, Della Mea Plentz R et al. Reduced venous endothelial responsiveness after oral lipid overload in healthy volunteers. Metabolism 2008; 57: 103-109
  • 38 Rubin D, Helwig U, Nothnagel M et al. Postprandial plasma adiponectin decreases after glucose and high fat meal and is independently associated with postprandial triacylglycerols but not with – 11388 promoter polymorphism. The British journal of nutrition 2008; 99: 76-82
  • 39 Musso G, Bo S, Cassader M et al. Impact of sterol regulatory element-binding factor-1c polymorphism on incidence of nonalcoholic fatty liver disease and on the severity of liver disease and of glucose and lipid dysmetabolism. The American journal of clinical nutrition 2013; 98: 895-906
  • 40 Peake PW, Kriketos AD, Campbell LV et al. The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals. Eur J Endocrinol 2005; 153: 409-417
  • 41 Bulcao C, Ferreira SR, Giuffrida FM et al. The new adipose tissue and adipocytokines. Current diabetes reviews 2006; 2: 19-28
  • 42 Zietz B, Herfarth H, Paul G et al. Adiponectin represents an independent cardiovascular risk factor predicting serum HDL-cholesterol levels in type 2 diabetes. FEBS Lett 2003; 545: 103-104
  • 43 Shaw KA, Hennebold JD, Edelman AB. Effect of a combined estrogen and progesterone oral contraceptive on circulating adipocytokines adiponectin, resistin and DLK-1 in normal and obese female rhesus monkeys. Contraception 2013; 88: 177-182
  • 44 Gursoy G, Esbah O, Kirnap NG et al. The relation of obesity with serum resistin levels in smoker and nonsmokers. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences 2012; 17: 119-122
  • 45 Cabrera de Leon A, Almeida Gonzalez D, Gonzalez Hernandez A et al. The association of resistin with coronary disease in the general population. Journal of atherosclerosis and thrombosis 2014; 21: 273-281
  • 46 Kappelle PJ, Dullaart RP, van Beek AP et al. The plasma leptin/adiponectin ratio predicts first cardiovascular event in men: a prospective nested case-control study. European journal of internal medicine 2012; 23: 755-759
  • 47 Jung CH, Rhee EJ, Choi JH et al. The relationship of adiponectin/leptin ratio with homeostasis model assessment insulin resistance index and metabolic syndrome in apparently healthy korean male adults. Korean diabetes journal 2010; 34: 237-243
  • 48 Singh P, Sridhar MG, Rajappa M et al. Adiponectin-resistin index and its strong association with acute coronary syndrome in South Indian men. Inflammation research: official journal of the European Histamine Research Society… [et al.] 2014; 63: 961-968
  • 49 Sarray S, Madan S, Saleh LR et al. Validity of adiponectin-to-leptin and adiponectin-to-resistin ratios as predictors of polycystic ovary syndrome. Fertility and sterility 2015;
  • 50 Romacho T, Sanchez-Ferrer CF, Peiro C. Visfatin/Nampt: an adipokine with cardiovascular impact. Mediators of inflammation 2013; 2013: 946427
  • 51 Schwartz DR, Lazar MA. Human resistin: found in translation from mouse to man. Trends Endocrinol Metab 2011; 22: 259-265
  • 52 Nagaev I, Smith U. Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 2001; 285: 561-564
  • 53 Savage DB, Sewter CP, Klenk ES et al. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 2001; 50: 2199-2202