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Leptin Signaling Could Mediate Hippocampal Decumulation of Beta-Amyloid and Tau Induced by High-Intensity Interval Training in Rats with Type 2 Diabetes

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Abstract

Leptin (LEP) can cross the blood–brain barrier and facilitate cross-talk between the adipose tissue and central nerve system (CNS). This study aimed to investigate the effect of 8-week high-intensity interval training (HIIT) on the LEP signaling in the hippocampus of rats with type 2 diabetes. 20 rats were randomly divided into four groups: (i) control (Con), (ii) type 2 diabetes (T2D), (iii) exercise (EX), and (iv) type 2 diabetes + exercise (T2D + EX). The rats in the T2D and T2D + EX were fed a high-fat diet for two months, then a single dose of STZ (35 mg/kg) was injected to induce diabetes. The EX and T2D + EX groups performed 4–10 intervals of treadmill running at 80–100% of Vmax. Serum and hippocampal levels of LEP as well as hippocampal levels of LEP receptors (LEP-R), Janus kinase 2 (JAK-2), signal transducer and activator of transcription 3 (STAT-3), activated protein kinase (AMP-K), proxy zoster receptor α (PGC-1α), beta-secretase 1 (BACE1), Beta-Amyloid (Aβ), Phosphoinositide 3-kinases (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), Glycogen Synthase Kinase 3 Beta (GSK3β), and hyperphosphorylated tau proteins (TAU) were measured. One-way ONOVA and Tukey post-hoc tests were used to analyze the data. Serum and hippocampal levels of LEP as well as hippocampal levels of LEP-R, JAK-2, STAT-3, AMP-K, PGC1α, PI3K, AKT, and mTOR were increased while hippocampal levels of BACE1, GSK3B, TAU, and Aβ were decreased in T2D + EX compared with T2D group. Serum LEP and hippocampal levels of LEP, LEP-R, JAK-2, STAT-3, AMP-K, PGC1α, PI3K, AKT, and mTOR were decreased. Conversely hippocampal levels of BACE1, GSK3B, TAU, and Aβ were increased in T2D group compared with CON group. HIIT could improve LEP signaling in the hippocampus of rats with type 2 diabetes and decrease the accumulation of Tau and Aβ, which may reduce the risk of memory impairments.

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Data Availability

Data that support the findings of this study are available at Kerman University of Medical Sciences.

Abbreviations

AMP:

Activated protein kinase

Aβ:

Beta-amyloid

BACE1:

Beta-secretase 1

BBB:

Blood–brain barrier

CDC:

Centers for disease control and prevention

CNS:

Central nerve system

CO:

Control

EX:

Exercise

GSK3β:

Glycogen synthase kinase 3 Beta

JAK-2:

Janus kinase 2

IR:

Insulin resistance

LEP:

Leptin

LEP-R:

Leptin receptor

LR:

Leptin resistance

MTOR:

Mammalian target of rapamycin

PKB/AKT:

Protein kinase B

PI3K:

Phosphoinositide 3-kinases

PGC1α:

Proxy zoster receptor α

STAT-3:

Signal transducer and activator of transcription 3

TAU:

Hyperphosphorylated tau proteins

T2D:

Type 2 diabetes

T2D + EX:

Type2 diabetes + exercise

WHO:

World Health Organization

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Acknowledgements

The authors would like to thank Neuroscience Research Center, Kerman University of Medical Sciences for its financial support. 

Funding

This research was funded by Neuroscience Research Center, Kerman University of Medical Sciences.

Author information

Author notes

  1. Maryam Hossein Rezaei and Elham Madadizadeh have contributed equally to this work.

  2. Mohsen Aminae and Mehdi Abbaspour have contributed equally to this work.

Authors and Affiliations

  1. Department of Exercise Physiology, Faculty of Physical Education, Shahid Bahonar University, Kerman, Iran

    Maryam Hossein Rezaei, Elham Madadizadeh, Mohsen Aminaei & Mehdi Abbaspoor

  2. Exercise Physiology and Metabolism (Sports Medicine), BaySpo—Bayreuth Centre of Sports Science, University of Bayreuht, Bayreuth, Germany

    Janis Schierbauer & Othmar Moser

  3. Interdisciplinary Metabolic Medicine Trials Unit, Medical University of Graz, Graz, Austria

    Othmar Moser

  4. Neuroscience Research Center, Institute of Neuropharmacology and Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Kayvan Khoramipour

  5. Aspetar Qatar Orthopaedic and Sports Medicine Hospital, Doha, Qatar

    Karim Chamari

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Contributions

Conceptualization, KK, Methodology, KK, Software, MA, Validation, MH, Formal Analysis, M.A, KC; Investigation, MH, Resources, EM, Data Curation, MA, Writing—Original Draft Preparation, EM, Writing—Review & Editing, KK, KC, Visualization, MA, KC, Supervision, KK, KC; Project Administration, KK, Funding Acquisition, KK.

Corresponding author

Correspondence to Kayvan Khoramipour.

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This study was approved by the Kerman University of Medical Sciences (IR.UK.REC.1400.008).

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Rezaei, M.H., Madadizadeh, E., Aminaei, M. et al. Leptin Signaling Could Mediate Hippocampal Decumulation of Beta-Amyloid and Tau Induced by High-Intensity Interval Training in Rats with Type 2 Diabetes. Cell Mol Neurobiol 43, 3465–3478 (2023). https://doi.org/10.1007/s10571-023-01357-1

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