Abstract
Fasting-induced adipose factor/angiopoietin-like protein 4 (FIAF/Angptl4) was recently
introduced as a novel adipokine influencing glucose and lipid homeostasis. In the
current study, we quantified circulating FIAF/Angtl4 levels in patients on chronic
hemodialysis (CD) as compared to controls with a glomerular filtration rate above
50 ml/min. FIAF/Angptl4 was determined by ELISA in control (n=60) and CD (n=60) patients
and correlated to clinical and biochemical measures of renal function, glucose and
lipid metabolism, as well as inflammation, in both groups. Median serum FIAF/Angptl4
levels were more than 5-fold higher in CD patients (48.3 μg/l) as compared to control
subjects (8.4 μg/l) (p<0.001). Furthermore, serum creatinine independently predicted
FIAF/Angptl4 concentrations in multiple regression analyses in control subjects (p<0.01).
In CD patients, C-reactive protein was independently and positively associated with
circulating FIAF/Angptl4 (p<0.01). Taken together, we show that serum FIAF/Angptl4
levels are significantly increased in end-stage renal disease and independently associated
with markers of renal function in control subjects.
Key words
FIAF/Angptl4 - hemodialysis - insulin resistance - obesity
References
- 1
Fasshauer M, Paschke R.
Regulation of adipocytokines and insulin resistance.
Diabetologia.
2003;
46
1594-1603
- 2
Trujillo ME, Scherer PE.
Adipose tissue-derived factors: impact on health and disease.
Endocr Rev.
2006;
27
762-778
- 3
Fasshauer M, Paschke R, Stumvoll M.
Adiponectin, obesity, and cardiovascular disease.
Biochimie.
2004;
86
779-784
- 4
Kralisch S, Sommer G, Deckert CM, Linke A, Bluher M, Stumvoll M, Fasshauer M.
Adipokines in diabetes and cardiovascular diseases.
Minerva Endocrinol.
2007;
32
161-171
- 5
Kersten S, Mandard S, Tan NS, Escher P, Metzger D, Chambon P, Gonzalez FJ, Desvergne B,
Wahli W.
Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated
receptor target gene.
J Biol Chem.
2000;
275
28488-28493
- 6
Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A, Friedman JM, Holmes WE,
Spiegelman BM.
Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related
protein associated with adipose differentiation.
Mol Cell Biol.
2000;
20
5343-5349
- 7
Dutton S, Trayhurn P.
Regulation of angiopoietin-like protein 4/fasting-induced adipose factor (Angptl4/FIAF)
expression in mouse white adipose tissue and 3T3-L1 adipocytes.
Br J Nutr.
2008;
100
18-26
- 8
Yamada T, Ozaki N, Kato Y, Miura Y, Oiso Y.
Insulin downregulates angiopoietin-like protein 4 mRNA in 3T3-L1 adipocytes.
Biochem Biophys Res Commun.
2006;
347
1138-1144
- 9
Yoshida K, Shimizugawa T, Ono M, Furukawa H.
Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and
inhibitor of lipoprotein lipase.
J Lipid Res.
2002;
43
1770-1772
- 10
Xu A, Lam MC, Chan KW, Wang Y, Zhang J, Hoo RL, Xu JY, Chen B, Chow WS, Tso AW, Lam KS.
Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance
but induces hyperlipidemia and hepatic steatosis in mice.
Proc Natl Acad Sci USA.
2005;
102
6086-6091
- 11
Mandard S, Zandbergen F, van Straten E, Wahli W, Kuipers F, Muller M, Kersten S.
The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated
with lipoproteins and governs plasma lipid levels and adiposity.
J Biol Chem.
2006;
281
934-944
- 12
Koliwad SK, Kuo T, Shipp LE, Gray NE, Backhed F, So AY, Farese Jr RV, Wang JC.
Angiopoietin-like 4 (ANGPTL4, fasting-induced adipose factor) is a direct glucocorticoid
receptor target and participates in glucocorticoid-regulated triglyceride metabolism.
J Biol Chem.
2009;
284
25593-25601
- 13
Stejskal D, Karpisek M, Reutova H, Humenanska V, Petzel M, Kusnierova P, Vareka I,
Varekova R, Stejskal P.
Angiopoietin-like protein 4: development, analytical characterization, and clinical
testing of a new ELISA.
Gen Physiol Biophys.
2008;
27
59-63
- 14
Kersten S, Lichtenstein L, Steenbergen E, Mudde K, Hendriks HF, Hesselink MK, Schrauwen P,
Muller M.
Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated
free fatty acids.
Arterioscler Thromb Vasc Biol.
2009;
29
969-974
- 15
Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS,
Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N,
Kihara S, Funahashi T, Matsuzawa Y.
Adiponectin, metabolic risk factors, and cardiovascular events among patients with
end-stage renal disease.
J Am Soc Nephrol.
2002;
13
134-141
- 16
Ziegelmeier M, Bachmann A, Seeger J, Lossner U, Kratzsch J, Bluher M, Stumvoll M,
Fasshauer M.
Serum levels of the adipokine RBP-4 in relation to renal function.
Diabetes Care.
2007;
30
2588-2592
- 17
Sommer G, Ziegelmeier M, Bachmann A, Kralisch S, Lossner U, Kratzsch J, Bluher M,
Stumvoll M, Fasshauer M.
Serum levels of adipocyte fatty acid binding protein are increased in chronic haemodialysis.
Clin Endocrinol (Oxf).
2008;
69
901-905
- 18
Pfau D, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M.
Serum levels of the adipokine chemerin in relation to renal function.
Diabetes Care.
2010;
33
171-173
- 19
Stein S, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M.
Serum levels of the adipokine FGF21 depend on renal function.
Diabetes Care.
2009;
32
126-128
- 20
Seeger J, Ziegelmeier M, Bachmann A, Lossner U, Kratzsch J, Bluher M, Stumvoll M,
Fasshauer M.
Serum levels of the adipokine vaspin in relation to metabolic and renal parameters.
J Clin Endocrinol Metab.
2008;
93
247-251
- 21
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC.
Homeostasis model assessment: insulin resistance and beta-cell function from fasting
plasma glucose and insulin concentrations in man.
Diabetologia.
1985;
28
412-419
- 22
Cumin F, Baum HP, Levens N.
Leptin is cleared from the circulation primarily by the kidney.
Int J Obes Relat Metab Disord.
1996;
20
1120-1126
- 23
Sharma K, Considine RV, Michael B, Dunn SR, Weisberg LS, Kurnik BR, Kurnik PB, O’Connor J,
Sinha M, Caro JF.
Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients.
Kidney Int.
1997;
51
1980-1985
- 24
Campean V, Neureiter D, Varga I, Runk F, Reiman A, Garlichs C, Achenbach S, Nonnast-Daniel B,
Amann K.
Atherosclerosis and vascular calcification in chronic renal failure.
Kidney Blood Press Res.
2005;
28
280-289
- 25
Folsom AR, Peacock JM, Demerath E, Boerwinkle E.
Variation in ANGPTL4 and risk of coronary heart disease: the Atherosclerosis Risk
in Communities Study.
Metabolism.
2008;
57
1591-1596
- 26
Adachi H, Fujiwara Y, Kondo T, Nishikawa T, Ogawa R, Matsumura T, Ishii N, Nagai R,
Miyata K, Tabata M, Motoshima H, Furukawa N, Tsuruzoe K, Kawashima J, Takeya M, Yamashita S,
Koh GY, Nagy A, Suda T, Oike Y, Araki E.
Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and
protects against atherosclerosis.
Biochem Biophys Res Commun.
2009;
379
806-811
1 These authors contributed equally to this work
Correspondence
M. Fasshauer
Liebigstraße 18
04103 Leipzig
Germany
Telefon: +49/341/971 3318
Fax: +49/341/971 3389
eMail: mathias.fasshauer@medizin.uni-leipzig.de