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. 2005 Aug;25(5):869–880. doi: 10.1007/s10571-005-4943-9

Early Neuroendocrine Alterations in Female Rats Following a Diet Moderately Enriched in Fat

George Soulis 1, Efthimia Kitraki 1, Kyriaki Gerozissis 2,
PMCID: PMC11529544  PMID: 16133939

Abstract

  1. High-fat diets disrupt metabolic equilibrium and hypothalamic-pituitary-adrenal axis function and may lead to the development of metabolic and endocrine dysfunctions. The early neuroendocrine responses elicited by a combination of short-term metabolic and emotional stressors is not fully elucidated.

  2. The purpose of the present study was to determine the impact on female rats, of a short-term enriched in fat diet, combined with an acute stressor.

  3. Adult female Wistar rats were fed a fat diet for 7 days and subsequently exposed to 5 min swimming stress. Plasma leptin, insulin, glucose, luteinizing hormone (LH) and corticosterone, along with brain corticosteroid receptors’ mRNAs were measured at 1 h post stress.

  4. Diet, compared to chow, reduced food intake and body weight gain, increased leptin and LH, and decreased glucose in the periphery. The diet increased plasma corticosterone and reduced GR mRNA in the hippocampus, similarly to swim stress.

  5. The diet significantly modified the animals’ response to the subsequent swim stress, by blocking further corticosterone rise and GR mRNA reduction. In addition, exposure of diet-fed rats to stress, altered their endocrine response, in terms of leptin and LH.

  6. These observations suggest that even short, moderately unbalanced diets can affect peripheral and central components of energy balance, reproduction and stress response.

Keywords: hippocampus, corticosteroid receptors, leptin, insulin, stress, dietary fat

References

  1. Ackroff, K., Vigorito, M., and Sclafani, A. (1990). Fat appetite in rats: The response of infant and adult rats to nutritive and non-nutritive oil emulsions. Appetite15:171–188. [DOI] [PubMed] [Google Scholar]
  2. Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., and Flier, J. S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature382:250–252. [DOI] [PubMed] [Google Scholar]
  3. Ainslie, D. A., Proietto, J., Fam, B. C., and Thorburn, A. W. (2000). Short-term, high-fat diets lower circulating leptin concentrations in rats. Am. J. Clin. Nutr. 71:438–442. [DOI] [PubMed] [Google Scholar]
  4. Anderwald, C., Muller, G., Koca, G., Furnsinn, C., Waldhausl, W., and Roden, M. (2002). Short-term leptin-dependent inhibition of hepatic gluconeogenesis is mediated by insulin receptor substrate-2. Mol. Endocrinol. 16:1612–1628. [DOI] [PubMed] [Google Scholar]
  5. Brann, D. W., and Mahesh, V. B. (1991). Role of corticosteroids in female reproduction. FASEB J. 5:2691–2698. [DOI] [PubMed] [Google Scholar]
  6. Burcelin, R., Thorens, B., Glauser, M., Gaillard, R. C., and Pralong, F. P. (2003). Gonadotropin-releasing hormone secretion from hypothalamic neurons: Stimulation by insulin and potentiation by leptin. Endocrinology144:4484–4491. [DOI] [PubMed] [Google Scholar]
  7. Buwalda, B., Blom, W. A., Koolhaas, J. M., and van Dijk, G. (2001). Behavioral and physiological responses to stress are affected by high-fat feeding in male rats. Physiol. Behav. 73:371–377. [DOI] [PubMed] [Google Scholar]
  8. Cagampang, F. R., Cates, P. S., Sandhu, S., Strutton, P. H., McGarvey, C., Coen, C. W., and O’Byrne, K. T. (1997). Hypoglycaemia-induced inhibition of pulsatile luteinizing hormone secretion in female rats: Role of oestradiol, endogenous opioids and the adrenal medulla. J. Neuroendocrinol. 9:867–872. [DOI] [PubMed] [Google Scholar]
  9. Chan, O., Inouye, K., Riddell, M. C., Vranic, M., and Matthews, S. G. (2003). Diabetes and the hypothalamo-pituitary-adrenal (HPA) axis. Minerva Endocrinol. 28:87–102. [PubMed] [Google Scholar]
  10. Chehab, F. F., Lim, M. E., and Lu, R. (1996). Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat. Genet. 12:318–320. [DOI] [PubMed] [Google Scholar]
  11. Cheung, C. C., Clifton, D. K., and Steiner, R. A. (2000). Perspectives on leptin’s role as a metabolic signal for the onset of puberty. Front. Horm. Res. 26:87–105. [DOI] [PubMed] [Google Scholar]
  12. Chomczynski, P., and Sacchi, N. (1987). Single-step method of RNA isolation by guanidnium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156–159. [DOI] [PubMed] [Google Scholar]
  13. Cruciani-Guglielmacci, C., Vincent-Lamon, M., Rouch, C., Orosco, M., Ktorza, A., and Magnan, C. (2004). Early change in insulin secretion and action induced by high fat diet and related to decreased sympathetic nervous system activity. Am. J. Physiol. Endo. Metab. (e-pub, September 7). [DOI] [PubMed]
  14. de Kloet, E. R. (2003). Hormones, brain and stress. Endocr. Regul. 37:51–68. [PubMed] [Google Scholar]
  15. Dong, Y., Poellinger, L., Gustafsson, J. A., and Okret, S. (1988). Regulation of glucocorticoid receptor expression: evidence for transcriptional and posttranslational mechanisms. Mol. Endocrinol. 2:1256–1264. [DOI] [PubMed] [Google Scholar]
  16. Frisch, R. E., Hegsted, D. M., and Yoshinaga, K. (1975). Body weight and food intake at early estrus of rats on a high-fat diet. Proc. Natl. Acad. Sci. U S A72:4172–4176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Giovambattista, A., Chisari, A. N., Gaillard, R. C., and Spinedi, E. (2000). Food intake-induced leptin secretion modulates hypothalamo-pituitary-adrenal axis response and hypothalamic Ob-Rb expression to insulin administration. Neuroendocrinology72:341–349. [DOI] [PubMed] [Google Scholar]
  18. Gotoh, M., Tajima, T., Suzuki, Y., Ikari, H., Iguchi, A., Kakumu, S., and Hirooka, Y. (1998). Swimming stress that causes hyperglycemia increases in vivo release of noradrenaline, but not acetylcholine, from the hypothalamus of conscious rats. Brain Res. 780:74–79. [DOI] [PubMed] [Google Scholar]
  19. Havel, P. J. (2001). Peripheral signals conveying metabolic information to the brain: Short-term and long-term regulation of food intake and energy homeostasis. Exp. Biol. Med. (Maywood)226:963–977. [DOI] [PubMed] [Google Scholar]
  20. Havel, P. J., Townsend, R., Chaump, L., and Teff, K. (1999). High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes48:334–341. [DOI] [PubMed] [Google Scholar]
  21. Heiman, M. L., Ahima, R. S., Craft, L. S., Schoner, B., Stephens, T. W., and Flier, J. S. (1997). Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology138:3859–3863. [DOI] [PubMed] [Google Scholar]
  22. Herman, J. P., Adams, D., and Prewitt, C. (1995). Regulatory changes in neuroendocrine stress-integrative circuitry produced by a variable stress paradigm. Neuroendocrinology61:180–190. [DOI] [PubMed] [Google Scholar]
  23. Kalra, S. P., Dube, M. G., Pu, S., Xu, B., Horvath, T. L., and Kalra P. S. (1999). Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr. Rev. 20:68–100. [DOI] [PubMed] [Google Scholar]
  24. Kamara, K., Eskay, R., and Castonguay, T. (1998). High-fat diets and stress responsivity. Physiol. Behav. 64:1–6. [DOI] [PubMed] [Google Scholar]
  25. Karandrea, D., Kittas, C., and Kitraki, E. (2002). Forced swimming differentially affects male and female brain corticosteroid receptors. Neuroendocrinology75:217–226. [DOI] [PubMed] [Google Scholar]
  26. Kellendonk, C., Eiden, S., Kretz, O., Schutz, G., Schmidt, I., Tronche, F., and Simon, E. (2002). Inactivation of the GR in the nervous system affects energy accumulation. Endocrinology143:2333–2340. [DOI] [PubMed] [Google Scholar]
  27. Kiess, W., Muller, G., Galler, A., Reich, A., Deutscher, J., Klammt, J., and Kratzsch, J. (2000). Body fat mass, leptin and puberty. J. Pediatr. Endocrinol. Metab. 13:717–722. [DOI] [PubMed] [Google Scholar]
  28. Kitraki, E., Karandrea, D., and Kittas, C. (1999). Long-lasting effects of stress on glucocorticoid receptor gene expression in the rat brain. Neuroendocrinology69:331–338. [DOI] [PubMed] [Google Scholar]
  29. Kitraki, E., Soulis, G., and Gerozissis, K. (2004). Impaired neuroendocrine response to stress following a short term fat-enriched diet. Neuroendocrinology79:338–345. [DOI] [PubMed] [Google Scholar]
  30. Kraegen, E. W., Clark, P. W., Jenkins, A. B., Daley, E. A., Chisholm, D. J., and Storlien, L. H. (1991). Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats. Diabetes40:1397–1403. [DOI] [PubMed] [Google Scholar]
  31. Makino, S., Hashimoto, K., and Gold, P. W. (2002). Multiple feedback mechanisms activating corticotropin-releasing hormone system in the brain during stress. Pharmacol. Biochem. Behav. 73:147–158. [DOI] [PubMed] [Google Scholar]
  32. Nagatani, S., Guthikonda, P., Thompson, R. C., Tsukamura, H., Maeda, K. I., and Foster, D. L. (1998). Evidence for GnRH regulation by leptin: Leptin administration prevents reduced pulsatile LH secretion during fasting. Neuroendocrinology67:370–376. [DOI] [PubMed] [Google Scholar]
  33. Pagano, C., Marzolo, M., Granzotto, M., Ricquier, D., Federspil, G., and Vettor, R. (1999). Acute effects of exercise on circulating leptin in lean and genetically obese fa/fa rats. Biochem. Biophys. Res. Commun. 255:698–702. [DOI] [PubMed] [Google Scholar]
  34. Pascoe, W. S., Smythe, G. A., and Storlien, L. H. (1991). Enhanced responses to stress induced by fat-feeding in rats: Relationship between hypothalamic noradrenaline and blood glucose. Brain Res. 550:192–196. [DOI] [PubMed] [Google Scholar]
  35. Pilkis, S. J., and Granner, D. K. (1992). Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu. Rev. Physiol. 54:885–909. [DOI] [PubMed] [Google Scholar]
  36. Rayner, D. V., and Trayhurn, P. (2001). Regulation of leptin production: Sympathetic nervous system interactions. J. Mol. Med. 79:8–20. [DOI] [PubMed] [Google Scholar]
  37. Sandoval, D. A., and Davis, S. N. (2003). Leptin: Metabolic control and regulation. J. Diab. Complications17:108–113. [DOI] [PubMed] [Google Scholar]
  38. Slieker, L. J., Sloop, K. W., Surfac, P. L., Kriauciunas, A., LaQuier, F., Manetta, J., Bue-Valleskey, J., and Stephens, T. W. (1996). Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J. Biol. Chem. 271:5301–5304. [DOI] [PubMed] [Google Scholar]
  39. Smythe, G. A., Pascoe, W. S., and Storlien, L. H. (1989). Hypothalamic noradrenergic and sympathoadrenal control of glycemia after stress. Am. J. Physiol. 256:E231–235. [DOI] [PubMed] [Google Scholar]
  40. Spinedi, E., and Gaillard, R. C. (1998). A regulatory loop between the hypothalamo-pituitary-adrenal (HPA) axis and circulating leptin: A physiological role of ACTH. Endocrinology139:4016–4020. [DOI] [PubMed] [Google Scholar]
  41. Strack, A. M., Horsley, C. J., Sebastian, R. J., Akana, S. F., and Dallman, M. F. (1995). Glucocorticoids and insulin: Complex interaction on brown adipose tissue. Am. J. Physiol. 268:R1209–1216. [DOI] [PubMed] [Google Scholar]
  42. Tannenbaum, B. M., Brindley, D. N., Tannenbaum, G. S., Dallman, M. F., McArthur, M. D., and Meaney, M. J. (1997). High-fat feeding alters both basal and stress-induced hypothalamic-pituitary-adrenal activity in the rat. Am. J. Physiol. 273:E1168–1177. [DOI] [PubMed] [Google Scholar]
  43. Unger, R. H., and Orci, L. (2001). Diseases of liporegulation: New perspective on obesity and related disorders. FASEB J. 15:312–321. [DOI] [PubMed] [Google Scholar]
  44. Wang, J., Obici, S., Morgan, K., Barzilai, N., Feng, Z., and Rossetti, L. (2001). Overfeeding rapidly induces leptin and insulin resistance. Diabetes50:2786–2791. [DOI] [PubMed] [Google Scholar]
  45. Watanobe, H. (2002). Leptin directly acts within the hypothalamus to stimulate gonadotrophin-releasing hormone secretion in vivo in rats. J. Physiol. 545:255–268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Webster, J. C., and Cidlowski, J. A (1994). Downregulation of the glucocorticoid receptor. A mechanism for physiological adaptation to hormones. Ann. N. Y. Acad. Sci. 746:216–220. [DOI] [PubMed] [Google Scholar]

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