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Chronic exposure to a high-fat diet affects stress axis function differentially in diet-induced obese and diet-resistant rats

International Journal of Obesity volume 34, pages 1218–1226 (2010)Cite this article

Subjects

Abstract

Objective:

Consumption of a high-fat (HF) diet is a contributing factor for the development of obesity. HF diet per se acts as a stressor, stimulating hypothalamo–pituitary–adrenal (HPA) axis activity resulting in elevated glucocorticoid levels; however, the mechanism behind this activation is unclear. We hypothesized that consumption of an HF diet activates HPA axis by increasing norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, leading to elevation in corticotrophin-releasing hormone (CRH) concentration in the median eminence (ME) resulting in elevated serum corticosterone (CORT).

Subjects:

To test this hypothesis, diet-induced obese (DIO) and diet-resistant (DR) rats were exposed to either chow or HF diet for 6 weeks.

Measurements:

At the end of 6 weeks, NE in the PVN was measured using HPLC, CRH in the ME, and CORT and leptin levels in the serum were measured using RIA and ELISA, respectively. The gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in NE synthesis, and leptin receptor in brainstem noradrenergic nuclei were also measured.

Results:

HF diet increased PVN NE in both DIO and DR rats (P<0.05). However, this was accompanied by increases in CRH and CORT secretion only in DR animals, but not in DIO rats. Leptin receptor mRNA levels in the brainstem noradrenergic areas were not affected in both DIO and DR rats. However, HF diet increased TH mRNA levels only in DIO rats.

Conclusion:

Significant differences occur in all the arms of HPA axis function between DIO and DR rats. Further studies are needed to determine whether this could be a causative factor or a consequence to obesity.

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Acknowledgements

This work was supported by NIH AG027697 and NSF IBN 0236385. AC Shin was supported by the MSU Biomedical Health Research Initiative. We thank Ms Katrina Linning for her technical help. We also thank Dr Soyeon Ahn, Michigan State University (currently an Assistant Professor at University of Miami) for her guidance on statistics.

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Authors and Affiliations

  1. Neuroendocrine Research Laboratory, Michigan State University, East Lansing, MI, USA

    A C Shin, S M J MohanKumar, M P Sirivelu & P S MohanKumar

  2. Neuroscience, Michigan State University, East Lansing, MI, USA

    A C Shin, S M J MohanKumar, J R Haywood, G D Fink & P S MohanKumar

  3. Comparative Medicine and Integrative Biology graduate programs, Michigan State University, East Lansing, MI, USA

    S M J MohanKumar, M P Sirivelu & P S MohanKumar

  4. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA

    S M J MohanKumar, J R Haywood & G D Fink

  5. Department of Pathobiology and of Diagnostic Investigation, Michigan State University, East Lansing, MI, USA

    M P Sirivelu & P S MohanKumar

  6. Department of Food and Human Nutrition, Michigan State University, Michigan State University, East Lansing, MI, USA

    K J Claycombe

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  1. A C Shin
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Correspondence to P S MohanKumar.

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Shin, A., MohanKumar, S., Sirivelu, M. et al. Chronic exposure to a high-fat diet affects stress axis function differentially in diet-induced obese and diet-resistant rats. Int J Obes 34, 1218–1226 (2010). https://doi.org/10.1038/ijo.2010.34

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