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High Intensity Interval Training can Ameliorate Hypothalamic Appetite Regulation in Male Rats with Type 2 Diabetes: The Role of Leptin

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Abstract

Disruption of leptin (LEP) signaling in the hypothalamus caused by type 2 diabetes (T2D) can impair appetite regulation. The aim of this study was to investigate whether the improvement in appetite regulation induced by high-intensity interval training (HIIT) in rats with T2D can be mediated by LEP signaling. In this study, 20 male Wister rats were randomly assigned to one of four groups: CO (non-type 2 diabetes control), T2D (type 2 diabetes), EX (non-type 2 diabetes exercise), and T2D + EX (type 2 diabetes + exercise).To induce T2D, a combination of a high-fat diet for 2 months and a single dose of streptozotocin (35 mg/kg) was administered. Rats in the EX and T2D + EX groups performed 4–10 intervals of treadmill running at 80–100% of their maximum velocity (Vmax). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum levels of insulin (INS) and LEP (LEPS) as well as hypothalamic expression of LEP receptors (LEP-R), Janus kinase 2 (JAK-2), signal transducer and activator of transcription 3 (STAT-3), neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin cocaine (POMC), amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1) were assessed. ANOVA and Tukey post hoc tests were used to compare the results between the groups. The levels of LEPS and INS, as well as the levels of LEP-R, JAK-2, STAT-3, POMC, and CART in the hypothalamus were found to be higher in the T2D + EX group compared to the T2D group. On the other hand, the levels of HOMA-IR, NPY, AGRP, SOCS3, and FOXO1 were lower in the T2D + EX group compared to the T2D group (P < 0.0001). The findings of this study suggest that HIIT may improve appetite regulation in rats with T2D, and LEP signaling may play a crucial role in this improvement.

Graphical Abstract

Graphical abstract (leptin signaling in the hypothalamus), Leptin (LEP), Leptin receptor (LEP-R), Janus kinase 2 (JAK2), Signal transducer and activator of transcription 3 (STAT3), expressing Neuropeptide Y (NPY), Agouti-related protein (AGRP), anorexigenic neurons (expressing pro-opiomelanocortin cocaine (POMC), Amphetamine-related transcript (CART), suppressor of cytokine signaling (SOCS3), forkhead box protein O1 (FOXO1).

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Data Availability

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

Abbreviations

AGRP:

Agouti-related protein

CART:

Amphetamine-related transcript

CON:

Non-type 2 diabetes control

EX:

Non-type 2 diabetes exercise

FOXO1:

Forkhead box protein O1

HIIT:

High-intensity interval training

INS-S:

Serum insulin levels

INS-H:

Hypothalamus insulin

JAK-2:

Janus kinase 2

LEP:

Leptin

NPY:

Neuropeptide Y

POMC:

Pro-opiomelanocortin cocaine

SOCS3:

Suppressor of cytokine signaling

STAT-3:

Signal transducer and activator of transcription 3

T2D:

Type 2 diabetes

T2D + EX:

Type 2 diabetes + exercise

Vmax :

Maximum velocity

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Acknowledgements

We would like to thanks Mohammad Amin Rajizadeh and Abbas Bejeshk for their help and support.

Funding

This research was supported by neuroscience research center, Kerman University of Medical Scinces (Project No: 400000089).

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Authors and Affiliations

  1. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Kayvan Khoramipour

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

    Maryam Hossein Rezaei & Elham Madadizadeh

  3. Student Research Committee, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Mahdieh Sadat Hosseini & Zahra Soltani

  4. Exercise Physiology and Metabolism (Sports Medicine), BaySpo-Bayreuth Centre of Sports Science, University of Bayreuth, Bayreuth, Germany

    Janis Schierbauer & Othmar Moser

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

    Othmar Moser

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  1. Kayvan Khoramipour
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Contributions

Conceptualization, KK; methodology, KK; software, MH; validation, MH; formal analysis, ZS; investigation, MH; resources, EM.; data curation, ZS ; writing—original draft preparation, EM; writing—review and editing, KK; visualization, ZS; supervision, KK; project administration, KK; funding acquisition, KK.

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Correspondence to Kayvan Khoramipour.

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Khoramipour, K., Rezaei, M.H., Madadizadeh, E. et al. High Intensity Interval Training can Ameliorate Hypothalamic Appetite Regulation in Male Rats with Type 2 Diabetes: The Role of Leptin. Cell Mol Neurobiol 43, 4295–4307 (2023). https://doi.org/10.1007/s10571-023-01421-w

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