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Updated: Jan 25, 2026

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
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Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT

Published on: January 7, 2018

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Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high-fat diet

Jiqu Xu1,2, Hui Gao3, Li Zhang4

  • 1Department of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, China.

Journal of Pineal Research
|May 4, 2019
PubMed

Insights

Melatonin (MLT) administration reversed cognitive decline in aged rats fed a high-fat diet. MLT improved brain insulin signaling, reduced neuroinflammation, and mitigated Alzheimer's disease hallmarks.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Pharmacology

Background:

  • Brain insulin resistance, driven by neuroinflammation and oxidative stress, is linked to neurodegeneration, including amyloid-beta (Aβ) accumulation and tau hyperphosphorylation.
  • High-fat diets (HFD) can induce insulin resistance and cognitive deficits, particularly in aged populations.

Purpose of the Study:

  • To investigate the effects of chronic melatonin (MLT) administration on HFD-induced brain insulin resistance and cognitive impairment in aged rats.
  • To explore MLT's impact on neuroinflammation, oxidative stress, and key molecular markers associated with neurodegeneration.

Main Methods:

  • Aged rats were fed a HFD, with chronic MLT supplementation administered to one group.
  • Cognitive function was assessed using a water maze test.
  • Brain insulin signaling, hippocampal oxidative stress, neuroinflammation markers (TNF-α, microglia, astrocytes), Aβ accumulation, tau phosphorylation, CREB activity, BDNF levels, and cholinergic neuronal activity were evaluated.

Main Results:

  • MLT attenuated peripheral insulin resistance and reduced hippocampal oxidative stress and neuroinflammation (decreased TNF-α, microglia, and astrocyte activation).
  • MLT prevented HFD-induced increases in Aβ accumulation and tau phosphorylation.
  • MLT restored impaired brain insulin signaling, normalized hippocampal long-term potentiation (LTP), and improved CREB activity, BDNF levels, and cholinergic neuronal function.

Conclusions:

  • Chronic melatonin administration demonstrates significant protective effects against HFD-induced cognitive decline in aged rats.
  • MLT's benefits are mediated through the restoration of brain insulin signaling pathways and reduction of neuroinflammation and oxidative stress.
Keywords:
TAU phosphorylationamyloid-βbrain insulin resistancecognition impairmentmelatoninneuroinflammationoxidative stress

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