Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm
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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.
KeywordsResistin Adiponectin Insulin action Circadian rhythm Feeding status
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.
- 7.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 143:998–1007CrossRefPubMedGoogle Scholar
- 10.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 98:2005–2010PubMedCrossRefGoogle Scholar
- 14.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 20:1595–1599PubMedGoogle Scholar
- 17.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 47:1847–1853CrossRefPubMedGoogle Scholar
- 30.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 276:25651–25653CrossRefPubMedGoogle Scholar
- 33.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 7:941–946PubMedCrossRefGoogle Scholar
- 34.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 8:1288–1295PubMedCrossRefGoogle Scholar