Abstract
Resistin and adiponectin are adipokines with postulated opposite functions. Resistin has been related with insulin resistance in obesity, while adiponectin could be associated to higher insulin sensitivity. We have determined whether the production of these two adipokines during the day is related to the feeding rhythm in rats. Resistin mRNA levels in adipose tissue correlated positively with the gastric contents and serum insulin concentration, showing higher levels during the dark phase (period of the highest food intake), especially in the mesenteric depot, while levels decreased during the light phase. The diurnal pattern of resistin expression was not directly reflected in the circulating levels, but it showed a 6-h delay and correlated negatively with the gastric contents and serum insulin. Adiponectin expression followed an opposite pattern, not apparently related to feeding or insulin release, and not translated into changes in circulating levels. Moreover, considering that insulin stimulates resistin expression and that circulating resistin follows a contrary circadian pattern in comparison to insulin, resistin, apart from its role in the increased insulin resistance associated to obesity, could also act as a putative modulator of insulin in the daily feeding/fasting rhythm through a negative feedback regulation of its action.
Similar content being viewed by others
References
Ahima RS, Flier JS (2000) Leptin. Annu Rev Physiol 62:413–437
Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, Scherer PE, Steppan CM, Ahima RS, Obici S, Rossetti L, Lazar MA (2004) Regulation of fasted blood glucose by resistin. Science 303:1195–1198
Bertile F, Raclot T (2004) Differences in mRNA expression of adipocyte-derived factors in response to fasting, refeeding and leptin. Biochim Biophys Acta 1683:101–109
Bertile F, Oudart H, Criscuolo F, Maho YL, Raclot T (2003) Hypothalamic gene expression in long-term fasted rats: relationship with body fat. Biochem Biophys Res Commun 303:1106–1113
Bluher M, Michael MD, Peroni OD, Ueki K, Carter N, Kahn BB, Kahn CR (2002) Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev Cell 3:25–38
Bogan JS, Lodish HF (1999) Two compartments for insulin-stimulated exocytosis in 3T3-L1 adipocytes defined by endogenous ACRP30 and GLUT4. J Cell Biol 146:609–620
Combs TP, Wagner JA, Berger J, Doebber T, Wang WJ, Zhang BB, Tanen M, Berg AH, O’Rahilly S, Savage DB, Chatterjee K, Weiss S, Larson PJ, Gottesdiener KM, Gertz BJ, Charron MJ, Scherer PE, Moller DE (2002) Induction of adipocyte complement-related protein of 30 kilodaltons by PPARgamma agonists: a potential mechanism of insulin sensitization. Endocrinology 143:998–1007
Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R (2002) Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 290:1084–1089
Felipe F, Bonet ML, Ribot J, Palou A (2004) Modulation of resistin expression by retinoic acid and vitamin A status. Diabetes 53:882–889
Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 98:2005–2010
Gavrila A, Peng CK, Chan JL, Mietus JE, Goldberger AL, Mantzoros CS (2003) Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns. J Clin Endocrinol Metab 88:2838–2843
Halleux CM, Takahashi M, Delporte ML, Detry R, Funahashi T, Matsuzawa Y, Brichard SM (2001) Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun 288:1102–1107
Havel PJ (2004) Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 53(Suppl 1):S143–S151
Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599
Kim KH, Lee K, Moon YS, Sul HS (2001) A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 276:11252–11256
Kim KH, Zhao L, Moon Y, Kang C, Sul HS (2004) Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity. Proc Natl Acad Sci U S A 101:6780–6785
Kitagawa Y, Bujo H, Takahashi K, Shibasaki M, Ishikawa K, Yagui K, Hashimoto N, Noda K, Nakamura T, Yano S, Saito Y (2004) Impaired glucose tolerance is accompanied by decreased insulin sensitivity in tissues of mice implanted with cells that overexpress resistin. Diabetologia 47:1847–1853
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Nogueiras R, Gualillo O, Caminos JE, Casanueva FF, Dieguez C (2003) Regulation of resistin by gonadal, thyroid hormone, and nutritional status. Obes Res 11:408–414
Nogueiras R, Gallego R, Gualillo O, Caminos JE, Garcia-Caballero T, Casanueva FF, Dieguez C (2003) Resistin is expressed in different rat tissues and is regulated in a tissue- and gender-specific manner. FEBS Lett 548:21–27
Oliver P, Pico C, Martinez N, Bonet ML, Palou A (2000) In vivo effects of CGP-12177 on the expression of leptin and uncoupling protein genes in mouse brown and white adipose tissues. Int J Obes Relat Metab Disord 24:423–428
Palou A, Serra F, Bonet ML, Pico C (2000) Obesity: molecular bases of a multifactorial problem. Eur J Nutr 39:127–144
Rajala MW, Qi Y, Patel HR, Takahashi N, Banerjee R, Pajvani UB, Sinha MK, Gingerich RL, Scherer PE, Ahima RS (2004) Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes 53:1671–1679
Ribot J, Felipe F, Bonet ML, Palou A (2001) Changes of adiposity in response to vitamin A status correlate with changes of PPAR gamma 2 expression. Obes Res 9:500–509
Sanchez J, Oliver P, Pico C, Palou A (2004) Diurnal rhythms of leptin and ghrelin in the systemic circulation and in the gastric mucosa are related to food intake in rats. Pflugers Arch 448:500–506
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312
Steppan CM, Wang J, Whiteman EL, Birnbaum MJ, Lazar MA (2005) Activation of SOCS-3 by resistin. Mol Cell Biol 25:1569–1575
Sul HS (2004) Resistin/ADSF/FIZZ3 in obesity and diabetes. Trends Endocrinol Metab 15:247–249
Ueno N, Dube MG, Inui A, Kalra PS, Kalra SP (2004) Leptin modulates orexigenic effects of ghrelin and attenuates adiponectin and insulin levels and selectively the dark-phase feeding as revealed by central leptin gene therapy. Endocrinology 145:4176–4184
Way JM, Gorgun CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, Oliver WR Jr, Willson TM, Kliewer SA, Hotamisligil GS (2001) Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 276:25651–25653
Winzell MS, Nogueiras R, Dieguez C, Ahren B (2004) Dual action of adiponectin on insulin secretion in insulin-resistant mice. Biochem Biophys Res Commun 321:154–160
Wolf G (2003) Adiponectin: a regulator of energy homeostasis. Nutr Rev 61:290–292
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946
Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295
Yildiz BO, Suchard MA, Wong ML, McCann SM, Licinio J (2004) Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity. Proc Natl Acad Sci U S A 101:10434–10439
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432
Zhang Y, Matheny M, Zolotukhin S, Tumer N, Scarpace PJ (2002) Regulation of adiponectin and leptin gene expression in white and brown adipose tissues: influence of beta3-adrenergic agonists, retinoic acid, leptin and fasting. Biochim Biophys Acta 1584:115–122
Zhang Y, Guo K-Y, Diaz PA, Heo M, Leibel RL (2002) Determinants of leptin gene expression in fat depots of lean mice. Am J Physiol Regul Integr Comp Physiol 282:R226–R234
Acknowledgements
This work was supported by the Spanish Government (grants G03/028, BFI2003-04439 and AGL 2004-07496/ALI). Our Laboratory is a member of the European Research Network of Excellence NuGO [The European Nutrigenomics Organization, EU Contract: FOOD-CT-2004-506360 NUGO (NOE)]. J.S. is a recipient of a fellowship from the Spanish Government.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Oliver, P., Ribot, J., Rodríguez, A.M. et al. Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm. Pflugers Arch - Eur J Physiol 452, 260–267 (2006). https://doi.org/10.1007/s00424-005-0034-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-005-0034-5