Effects of hydrocortisone administration on leptin and adiponectin synthesis in dogs

Hye-Ryung Choo 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Hye-Ryung Choo in
Current site
Google Scholar
PubMed
Close
 DVM, MS
,
Hakhyun Kim 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Hakhyun Kim in
Current site
Google Scholar
PubMed
Close
 DVM, MS
,
Ji-Houn Kang 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Ji-Houn Kang in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Chan-Joo Sung 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Chan-Joo Sung in
Current site
Google Scholar
PubMed
Close
 DVM, MS
,
Changhwan Ahn 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Changhwan Ahn in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Byeong-Teck Kang 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Byeong-Teck Kang in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Dongwoo Chang 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Dongwoo Chang in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Eui-Bae Jeung 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Eui-Bae Jeung in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
, and
Mhan-Pyo Yang 1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
1College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Search for other papers by Mhan-Pyo Yang in
Current site
Google Scholar
PubMed
Close
 DVM, PhD

Abstract

OBJECTIVE

To determine effects of hydrocortisone administration on serum leptin and adiponectin concentrations, abdominal fat distribution, and mRNA expression of leptin and adiponectin in abdominal adipose tissue of dogs.

ANIMALS

12 healthy dogs.

PROCEDURES

Dogs received hydrocortisone (8.5 mg/kg; n = 6) or a placebo (6) orally every 12 hours for 90 days. Serum leptin and adiponectin concentrations were measured with a canine-specific ELISA on the day before (day 0; baseline) and during (days 1, 3, 7, 30, 60, and 90) administration. On days 0, 30, 60, and 90, abdominal fat mass was quantified with CT, and mRNA expression of leptin and adiponectin in abdominal fat was analyzed by use of a PCR assay.

RESULTS

Hydrocortisone administration resulted in an increase in visceral fat mass on days 60 and 90, compared with the mass at baseline. Visceral fat mass at the level of L3 increased during hydrocortisone administration. Serum leptin concentration began to increase on day 1 and was significantly higher than the baseline concentration on days 30 and 60. Serum adiponectin concentration on days 30, 60, and 90 was significantly lower than the baseline concentration. Leptin and adiponectin mRNA expression in abdominal fat was greater on day 30, compared with expression at baseline, but lower on days 60 and 90, compared with expression on day 30. Serum leptin concentration and visceral fat mass were correlated.

CONCLUSIONS AND CLINICAL RELEVANCE

Hydrocortisone administration affected abdominal fat distribution and serum leptin and adiponectin concentrations through dysregulation of leptin and adiponectin expression.

Abstract

OBJECTIVE

To determine effects of hydrocortisone administration on serum leptin and adiponectin concentrations, abdominal fat distribution, and mRNA expression of leptin and adiponectin in abdominal adipose tissue of dogs.

ANIMALS

12 healthy dogs.

PROCEDURES

Dogs received hydrocortisone (8.5 mg/kg; n = 6) or a placebo (6) orally every 12 hours for 90 days. Serum leptin and adiponectin concentrations were measured with a canine-specific ELISA on the day before (day 0; baseline) and during (days 1, 3, 7, 30, 60, and 90) administration. On days 0, 30, 60, and 90, abdominal fat mass was quantified with CT, and mRNA expression of leptin and adiponectin in abdominal fat was analyzed by use of a PCR assay.

RESULTS

Hydrocortisone administration resulted in an increase in visceral fat mass on days 60 and 90, compared with the mass at baseline. Visceral fat mass at the level of L3 increased during hydrocortisone administration. Serum leptin concentration began to increase on day 1 and was significantly higher than the baseline concentration on days 30 and 60. Serum adiponectin concentration on days 30, 60, and 90 was significantly lower than the baseline concentration. Leptin and adiponectin mRNA expression in abdominal fat was greater on day 30, compared with expression at baseline, but lower on days 60 and 90, compared with expression on day 30. Serum leptin concentration and visceral fat mass were correlated.

CONCLUSIONS AND CLINICAL RELEVANCE

Hydrocortisone administration affected abdominal fat distribution and serum leptin and adiponectin concentrations through dysregulation of leptin and adiponectin expression.

Contributor Notes

Drs. Choo and Kim contributed equally to the manuscript.

Address correspondence to Dr. J-H. Kang (jhkang@chungbuk.ac.kr).
  • 1. Radin MJ, Sharkey LC, Holycross BJ. Adipokines: a review of biological and analytical principles and an update in dogs, cats, and horses. Vet Clin Pathol 2009;38:136156.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Caro JF, Sinha MK, Kolaczynski JW, et al. Leptin: the tale of an obesity gene. Diabetes 1996;45:14551462.

  • 3. Masuzaki H, Ogawa Y, Hosoda K, et al. Glucocorticoid regulation of leptin in Cushing's syndrome. J Clin Endocrinol Metab 1997;82:25422547.

    • Search Google Scholar
    • Export Citation
  • 4. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab 2003;88:55935602.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Andrews RC, Walker BR. Glucocorticoids and insulin resistance; old hormones, new targets. Clin Sci (Lond) 1999;96:513523.

  • 6. Arnaldi G, Scandali VM, Trementino L, et al. Pathophysiology of dyslipidemia in Cushing's syndrome. Neuroendocrinology 2010;92(suppl 1):86–90.

    • Search Google Scholar
    • Export Citation
  • 7. Vegiopoulos A, Herzig S. Glucocorticoids, metabolism and metabolic diseases. Mol Cell Endocrinol 2007;275:4361.

  • 8. Chanson P, Salenave S. Metabolic syndrome in Cushing's syndrome. Neuroendocrinology 2010;92(suppl 1):96–101.

  • 9. Ferraù F, Korbonits M. Metabolic comorbidities in Cushing's syndrome. Eur J Endocrinol 2015;173:M133M157.

  • 10. Mayo-Smith W, Hayes CW, Biller BM, et al. Body fat distribution measured with CT: correlations in healthy subjects, patients with anorexia nervosa, and patients with Cushing syndrome. Radiology 1989;170:515518.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Rockall AG, Sohaib SA, Evans D, et al. Computed tomography assessment of fat distribution in male and female patients with Cushing's syndrome. Eur J Endocrinol 2003;149:561567.

    • Search Google Scholar
    • Export Citation
  • 12. Vega GL, Grundy SM. Metabolic risk susceptibility in men is partially related to adiponectin/leptin ratio. J Obes 2013;2013:409679.

  • 13. Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001;50:11261133.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. Houseknecht KL, Portocarrero CP. Leptin and its receptors: regulators of whole-body energy homeostasis. Domest Anim Endocrinol 1998;15:457475.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:1069710703.

  • 16. Cano P, Cardinali DP, Ríos-Lugo MJ, et al. Effect of a high-fat diet on 24-hour pattern of circulating adipocytokines in rats. Obesity (Silver Spring) 2009;17:18661871.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Verkest KR, Rose FJ, Fleeman LM, et al. Adiposity and adiponectin in dogs: investigation of causes of discrepant results between two studies. Domest Anim Endocrinol 2011;41:3541.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Fallo F, Scarda A, Sonino N, et al. Effect of glucocorticoids on adiponectin: a study in healthy subjects and in Cushing's syndrome. Eur J Endocrinol 2004;150:339344.

    • Search Google Scholar
    • Export Citation
  • 19. Cho KD, Paek J, Kang JH, et al. Serum adipokine concentrations in dogs with naturally occurring pituitary-dependent hyperadrenocorticism. J Vet Intern Med 2014;28:429436.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Lubkowska A, Radecka A, Bryczkowska I, et al. Serum adiponectin and leptin concentrations in relation to body fat distribution, hematological indices and lipid profile in humans. Int J Environ Res Public Health 2015;12:1152811548.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. National Research Council. Guide for the care and use of laboratory animals. National Academy Press: Washington, DC, 1996.

  • 22. Kook PH, Schellenberg S, Grest P, et al. Microbiologic evaluation of gallbladder bile of healthy dogs and dogs with iatrogenic hypercortisolism: a pilot study. J Vet Intern Med 2010;24:224228.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Kook PH, Schellenberg S, Rentsch KM, et al. Effects of iatrogenic hypercortisolism on gallbladder sludge formation and biochemical bile constituents in dogs. Vet J 2012;191:225230.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Ishioka K, Okumura M, Sagawa M, et al. Computed tomographic assessment of body fat in Beagles. Vet Radiol Ultrasound 2005;46:4953.

  • 25. Nishii N, Takasu M, Ohba Y, et al. Effects of administration of glucocorticoids and feeding status on plasma leptin concentrations in dogs. Am J Vet Res 2006;67:266270.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Tvarijonaviciute A. Martínez-Subiela, Ceron JJ. Validation of 2 commercially available enzyme-linked immunosorbent assays for adiponectin determination in canine serum samples. Can J Vet Res 2010;74:279285.

    • Search Google Scholar
    • Export Citation
  • 27. Lee GS, Hong EJ, Gwak KS, et al. The essential oils of Chamaecyparis obtusa promote hair growth through the induction of vascular endothelial growth factor gene. Fitoterapia 2010;81:1724.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Vo TT, An BS, Yang H, et al. Calbindin-D9k as a sensitive molecular biomarker for evaluating the synergistic impact of estrogenic chemicals on GH3 rat pituitary cells. Int J Mol Med 2012;30:12331240.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Ishioka K, Soliman MM, Honjoh T, et al. Dexamethasone increases serum leptin concentration in dogs. Vet J 2002;164:295297.

  • 30. De Vos P, Saladin R, Auwerx J, et al. Induction of ob gene expression by corticosteroids is accompanied by body weight loss and reduced food intake. J Biol Chem 1995;270:1595815961.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Murakami T, Iida M, Shima K. Dexamethasone regulates obese expression in isolated rat adipocytes. Biochem Biophys Res Commun 1995;214:12601267.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Slieker LJ, Sloop KW, Surface PL, et al. Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem 1996;271:53015304.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Newcomer JW, Selke G, Melson AK, et al. Dose-dependent cortisol-induced increases in plasma leptin concentration in healthy humans. Arch Gen Psychiatry 1998;55:9951000.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Krsek M, Silha JV, Jezkova J, et al. Adipokine levels in Cushing's syndrome; elevated resistin levels in female patients with Cushing's syndrome. Clin Endocrinol (Oxf) 2004;60:350357.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Widjaja A, Schürmeyer TH, Von zur Mühlen A, et al. Determinants of serum leptin levels in Cushing's syndrome. J Clin Endocrinol Metab 1998;83:600603.

    • Search Google Scholar
    • Export Citation
  • 36. Veldman RG, Frölich M, Pincus SM, et al. Hyperleptinemia in women with Cushing's disease in driven by high-amplitude pulsatile, but orderly and eurhythmic, leptin secretion. Eur J Endocrinol 2001;144:2127.

    • Search Google Scholar
    • Export Citation
  • 37. Geer EB, Shen W, Gallagher D, et al. MRI assessment of lean and adipose tissue distribution in female patients with Cushing's disease. Clin Endocrinol (Oxf) 2010;73:469475.

    • Search Google Scholar
    • Export Citation
  • 38. Sukumaran S, Dubois DC, Jusko WJ, et al. Glucocorticoid effects on adiponectin expression. Vitam Horm 2012;90:163186.

  • 39. Verkest KR, Fleeman LM, Morton JM, et al. Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like peptide-1 using path analysis. Domest Anim Endocrinol 2011;41:2434.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40. Shi JH, Du WH, Liu XY, et al. Glucocorticoids decrease serum adiponectin level and WAT adiponectin mRNA expression in rats. Steroids 2010;75:853858.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41. Ryan VH, German AJ, Wood IS, et al. Adipokine expression and secretion by canine adipocytes: stimulation of inflammatory adipokine production by LPS and TNFα. Pflugers Arch 2010;460:603616.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42. Shuster A, Patlas M, Pinthus JH, et al. The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. Br J Radiol 2012;85:110.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement