Advertisement

Journal of Cell Communication and Signaling

, Volume 12, Issue 2, pp 433–439 | Cite as

Extra-adrenal glucocorticoids contribute to the postprandial increase of circulating leptin in mice

  • Yuka Tomabechi
  • Takeshi Tsuruta
  • Shinichi Saito
  • Martin Wabitsch
  • Kei SonoyamaEmail author
Research Article
  • 271 Downloads

Abstract

Leptin, an adipokine secreted by white adipocytes, is known for its function in regulating food intake and energy expenditure, but the mechanisms regulating its circulating levels is not fully understood. Our previous findings suggest that as yet unidentified humoral factors released from enterocytes are involved. The present study tested glucocorticoids (GCs) as candidate factors. Supplementation of corticosterone and cortisol promoted leptin production in murine adipocytes from the 3T3-L1 cell strain and human adipocytes from the Simpson Golabi–Behmel syndrome (SGBS) cell strain, respectively. These changes were observed in the absence but not presence of the GC-receptor antagonist mifepristone. The cortisol concentration in conditioned medium (CM) of human enterocyte-like Caco-2 cells was increased by phorbol-12-myristate 13-acetate and decreased by metyrapone. When SGBS adipocytes were cultured in these CMs, leptin production was positively associated with cortisol concentrations. During a 2-h refeeding after fasting, plasma leptin levels continued to increase in sham-operated mice, transiently increased at 60 min in adrenalectomized mice, and were unchanged in mifepristone-administered mice. These results suggest that extra-adrenal GCs contribute to the GC-receptor signaling-dependent increase of postprandial circulating leptin, whereas further studies will be required to determine whether enterocytes participate in the GCs-mediated increase of postprandial circulating leptin.

Keywords

Leptin Adipocyte Glucocorticoid Enterocyte 

Abbreviations

B6

C57BL/6

CM

Conditioned medium

GC

Glucocorticoid

MET

Metyrapone

Mif

Mifepristone

PMA

Phorbol-12-myristate 13-acetate

RT-qPCR

Real-time quantitative PCR

SGBS

Simpson Golabi–Behmel syndrome

Notes

Acknowledgments

This study was supported in part by the Regional Innovation Strategy Support Program of the MEXT, and by the Center of Innovation Program Trial, Japan Science and Technology Agency.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to disclose.

References

  1. Ahrén B, Månsson S, Gingerich RL, Havel PJ (1997) Regulation of plasma leptin in mice: influence of age, high-fat diet and fasting. Am J Physiol Regul Integr Comp Physiol 273:R113–R120CrossRefGoogle Scholar
  2. Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau JP, Bortoluzzi MN, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin MJ (1998) The stomach is a source of leptin. Nature 394:790–793CrossRefPubMedGoogle Scholar
  3. Boden G, Chen X, Mozzoli M, Ryan I (1996) Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 81:3419–3423PubMedGoogle Scholar
  4. Cima I, Corazza N, Dick B, Fuhrer A, Herren S, Jakob S, Ayuni E, Mueller C, Brunner T (2004) Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation. J Exp Med 200:1635–1646CrossRefPubMedPubMedCentralGoogle Scholar
  5. Frederich RC, Hamann A, Anderson S, Löllmann B, Lowell BB, Flier JS (1995) Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med 1:1311–1314CrossRefPubMedGoogle Scholar
  6. Fukuda H, Iritani N (1999) Regulation of ATP citrate-lyase gene expression in hepatocytes and adipocytes in normal and genetically obese rats. J Biochem 126:437–444CrossRefPubMedGoogle Scholar
  7. Hamilton BS, Paglia D, Kwan AY, Deitel M (1995) Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med 1:953–956CrossRefPubMedGoogle Scholar
  8. Hansen GH, Niels-Christiansen LL, Danielsen EM (2008) Leptin and the obesity receptor (OB-R) in the small intestine and colon: a colocalization study. J Histochem Cytochem 56:677–685CrossRefPubMedPubMedCentralGoogle Scholar
  9. Hardie LJ, Rayner DV, Holmes S, Trayhurn P (1996) Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochem Biophys Res Commun 223:660–665CrossRefPubMedGoogle Scholar
  10. Ishihara R, Mizuno Y, Miwa A, Hamada A, Tsuruta T, Wabitsch M, Sonoyama K (2015) Intestinal epithelial cells promote secretion of leptin and adiponectin in adipocytes. Biochem Biophys Res Commun 458:362–368CrossRefPubMedGoogle Scholar
  11. Jahng JW, Kim NY, Ryu V, Yoo SB, Kim BT, Kang DW, Lee JH (2008) Dexamethasone reduces food intake, weight gain and the hypothalamic 5-HT concentration and increases plasma leptin in rats. Eur J Pharmacol 581:64–70CrossRefPubMedGoogle Scholar
  12. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, Kern PA, Friedman JM (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1:1155–1161CrossRefPubMedGoogle Scholar
  13. Mueller M, Atanasov A, Cima I, Corazza N, Schoonjans K, Brunner T (2007) Differential regulation of glucocorticoid synthesis in murine intestinal epithelial versus adrenocortical cell lines. Endocrinology 148:1445–1453CrossRefPubMedGoogle Scholar
  14. Murakami T, Iida M, Shima K (1995) Dexamethasone regulates obese expression in isolated rat adipocytes. Biochem Biophys Res Commun 214:126–127CrossRefGoogle Scholar
  15. Pan H, Guo J, Su Z (2014) Advances in understanding the interrelations between leptin resistance and obesity. Physiol Behav 130:157–169CrossRefPubMedGoogle Scholar
  16. Phrakonkham P, Viengchareun S, Belloir C, Lombès M, Artur Y, Canivenc-Lavier MC (2008) Dietary xenoestrogens differentially impair 3T3-L1 preadipocyte differentiation and persistently affect leptin synthesis. J Steroid Biochem Mol Biol 110:95–103CrossRefPubMedGoogle Scholar
  17. Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girard J, Staels B, Auwerx J (1995) Transient increase in obese gene expression after food intake or insulin administration. Nature 377:527–529CrossRefPubMedGoogle Scholar
  18. Sangild PT, Hilsted L, Nexo E, Fowden AL, Silver M (1995) Vaginal birth versus elective caesarean section: effects on gastric function in the neonate. Exp Physiol 80:147–157CrossRefPubMedGoogle Scholar
  19. Seckl JR, Walker BR (2001) Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action. Endocrinology 142:1371–1376CrossRefPubMedGoogle Scholar
  20. Sidler D, Renzulli P, Schnoz C, Berger B, Schneider-Jakob S, Flück C, Inderbitzin D, Corazza N (2011) Colon cancer cells produce immunoregulatory glucocorticoids. Oncogene 30:2411–2419CrossRefPubMedGoogle Scholar
  21. Slieker LJ, Sloop KW, Surface PL, Kriauciunas A, LaQuier F, Manetta J, Bue-Valleskey J, Stephens TW (1996) Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem 271:5301–5304CrossRefPubMedGoogle Scholar
  22. Sobhani I, Bado A, Vissuzaine C, Buyse M, Kermorgant S, Laigneau JP, Attoub S, Lehy T, Henin D, Mignon M, Lewin MJ (2000) Leptin secretion and leptin receptor in the human stomach. Gut 47:178–183CrossRefPubMedPubMedCentralGoogle Scholar
  23. Stelmanska E, Kmiec Z, Swierczynski J (2012) The gender- and fat depot-specific regulation of leptin, resistin and adiponectin genes expression by progesterone in rat. J Steroid Biochem Mol Biol 132:160–167CrossRefPubMedGoogle Scholar
  24. Uchoa ET, Silva LE, de Castro M, Antunes-Rodrigues J, Elias LL (2012) Glucocorticoids are required for meal-induced changes in the expression of hypothalamic neuropeptides. Neuropeptides 46:119–124CrossRefPubMedGoogle Scholar
  25. Wabitsch M, Jensen PB, Blum WF, Christoffersen CT, Englaro P, Heinze E, Rascher W, Teller W, Tornqvist H, Hauner H (1996) Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 45:1435–1438CrossRefPubMedGoogle Scholar
  26. Wabitsch M, Brenner RE, Melzner I, Braun M, Möller P, Heinze E, Debatin KM, Hauner H (2001) Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation. Int J Obes 25:8–15CrossRefGoogle Scholar
  27. Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L (1998) A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature 393:684–688CrossRefPubMedGoogle Scholar
  28. Weigle DS, Duell PB, Connor WE, Steiner RA, Soules MR, Kuijper JL (1997) Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab 82:561–565PubMedGoogle Scholar
  29. Wellhoener P, Fruehwald-Schultes B, Kern W, Dantz D, Kerner W, Born J, Fehm HL, Peters A (2000) Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans. J Clin Endocrinol Metab 85:1267–1271CrossRefPubMedGoogle Scholar
  30. Zhang L, Lee JE, Wilusz J, Wilusz CJ (2008) The RNA-binding protein CUGBP1 regulates stability of tumor necrosis factor mRNA in muscle cells: implications for myotonic dystrophy. J Biol Chem 283:22457–22463CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The International CCN Society 2017

Authors and Affiliations

  • Yuka Tomabechi
    • 1
  • Takeshi Tsuruta
    • 2
  • Shinichi Saito
    • 3
  • Martin Wabitsch
    • 4
  • Kei Sonoyama
    • 5
    Email author
  1. 1.Graduate School of Life ScienceHokkaido UniversitySapporoJapan
  2. 2.Graduate School of Environmental and Life ScienceOkayama UniversityOkayamaJapan
  3. 3.Graduate School of MedicineYamaguchi UniversityUbeJapan
  4. 4.Department of Pediatrics and Adolescent MedicineUniversity of UlmUlmGermany
  5. 5.Laboratory of Food Biochemistry, Research Faculty of AgricultureHokkaido UniversitySapporoJapan

Personalised recommendations