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Consumption of a high-fat diet induces central insulin resistance independent of adiposity.

Publication ,  Journal Article
Clegg, DJ; Gotoh, K; Kemp, C; Wortman, MD; Benoit, SC; Brown, LM; D'Alessio, D; Tso, P; Seeley, RJ; Woods, SC
Published in: Physiol Behav
April 18, 2011

Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of LF and chow rats but had no effect on HF rats in either the chronic or the acute experiment. Rats chronically pair-fed the HF diet to match the caloric intake of LF rats, and with body weights and adiposity levels comparable to those of LF rats, were also unresponsive to i3vt insulin when returned to ad libitum food whereas rats pair-fed the LF diet had reduced food intake and body weight when administered i3vt insulin. Insulin's inability to reduce food intake in the presence of the high-fat diet was associated with a reduced ability of insulin to activate its signaling cascade, as measured by pAKT. Finally, i3vt administration of insulin increased hypothalamic expression of POMC mRNA in the LF- but not the HF-fed rats. We conclude that consumption of a HF diet leads to central insulin resistance following short exposure to the diet, and as demonstrated by reductions in insulin signaling and insulin-induced hypothalamic expression of POMC mRNA.

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Published In

Physiol Behav

DOI

EISSN

1873-507X

Publication Date

April 18, 2011

Volume

103

Issue

1

Start / End Page

10 / 16

Location

United States

Related Subject Headings

  • Time Factors
  • Signal Transduction
  • Rats, Long-Evans
  • Rats
  • RNA, Messenger
  • Pro-Opiomelanocortin
  • Neuropeptide Y
  • Male
  • Insulin Resistance
  • Insulin
 

Citation

APA
Chicago
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Clegg, D. J., Gotoh, K., Kemp, C., Wortman, M. D., Benoit, S. C., Brown, L. M., … Woods, S. C. (2011). Consumption of a high-fat diet induces central insulin resistance independent of adiposity. Physiol Behav, 103(1), 10–16. https://doi.org/10.1016/j.physbeh.2011.01.010
Clegg, Deborah J., Koro Gotoh, Christopher Kemp, Matthew D. Wortman, Stephen C. Benoit, Lynda M. Brown, David D’Alessio, Patrick Tso, Randy J. Seeley, and Stephen C. Woods. “Consumption of a high-fat diet induces central insulin resistance independent of adiposity.Physiol Behav 103, no. 1 (April 18, 2011): 10–16. https://doi.org/10.1016/j.physbeh.2011.01.010.
Clegg DJ, Gotoh K, Kemp C, Wortman MD, Benoit SC, Brown LM, et al. Consumption of a high-fat diet induces central insulin resistance independent of adiposity. Physiol Behav. 2011 Apr 18;103(1):10–6.
Clegg, Deborah J., et al. “Consumption of a high-fat diet induces central insulin resistance independent of adiposity.Physiol Behav, vol. 103, no. 1, Apr. 2011, pp. 10–16. Pubmed, doi:10.1016/j.physbeh.2011.01.010.
Clegg DJ, Gotoh K, Kemp C, Wortman MD, Benoit SC, Brown LM, D’Alessio D, Tso P, Seeley RJ, Woods SC. Consumption of a high-fat diet induces central insulin resistance independent of adiposity. Physiol Behav. 2011 Apr 18;103(1):10–16.
Journal cover image

Published In

Physiol Behav

DOI

EISSN

1873-507X

Publication Date

April 18, 2011

Volume

103

Issue

1

Start / End Page

10 / 16

Location

United States

Related Subject Headings

  • Time Factors
  • Signal Transduction
  • Rats, Long-Evans
  • Rats
  • RNA, Messenger
  • Pro-Opiomelanocortin
  • Neuropeptide Y
  • Male
  • Insulin Resistance
  • Insulin