Research Article

In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet

Volume: 52 August 24, 2026
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In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet

Abstract

Diet-induced obesity disrupts arcuate nucleus (ARC) hormonal signalling, including the development of ghrelin and leptin resistance, phenomena well-characterised in canonical AgRP/NPY neurons but largely unexplored in other orexigenic ARC populations. Tyrosine hydroxylase (TH)-expressing ARC neurons represent one such population with established roles in feeding control, yet whether chronic high-fat diet (HFD) exposure impairs their responsiveness to ghrelin and leptin in vivo remains unknown. Here, we investigated how HFD shapes ARC TH neuron Ca²⁺ dynamics across feeding-related states and during acute hormonal challenges using fibre photometry in freely moving TH-Cre mice. A total of 11 male TH-Cre mice were maintained on standard diet (SD, n=5) or HFD (n=6) for three months. A Cre-dependent AAV.Syn.Flex.GCaMP6s virus was injected into the ARC, followed by optical fibre implantation. After at least two weeks of expression, in vivo fiber photometry recordings were performed. Fluorescence signals were calculated as ΔF/F and summarized as area under the curve per minute (AUC/min). Basal activity was assessed during baseline (P1), food exposure (P2), and digestion (P3) under fed and fasted conditions. For hormonal challenges, fed mice received intraperitoneal ghrelin (1 mg/kg) and fasted mice received leptin (5 mg/kg), with analyses conducted across P1–P4 epochs. Basal ARC TH activity was comparable between chow and HFD groups across P1–P3 in both metabolic states. Ghrelin significantly increased ARC TH activity during P2 in chow controls, whereas this response was attenuated in HFD mice (p = 0.043). Leptin produced modest and similar effects in both groups. Chronic HFD selectively blunts ghrelin-evoked activation of ARC TH neurons while largely preserving basal activity and leptin responsiveness.

Keywords

Supporting Institution

Yeditepe University

Ethical Statement

All animal experiments were reviewed and approved by the Local Animal Experiments Ethics Committee of Yeditepe University (YÜDETAM). The study protocol was approved on January 27, 2023, under Protocol No: 2023-02 and Decision No: 2023/01-02.

References

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Details

Primary Language

English

Subjects

Endocrinology

Journal Section

Research Article

Publication Date

August 24, 2026

Submission Date

February 25, 2026

Acceptance Date

July 7, 2026

Published in Issue

Year 2026 Volume: 52

APA
Sümer, E., Gören, H., Barın, B., Kosif, Y., Başer, Ö., Keleştemur, M., Yavuz, Y., Gül, Z., & Yılmaz, B. (2026). In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet. Journal of Uludağ University Medical Faculty, 52. https://doi.org/10.32708/uutfd.1896815
AMA
1.Sümer E, Gören H, Barın B, et al. In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet. Journal of Uludağ University Medical Faculty. 2026;52. doi:10.32708/uutfd.1896815
Chicago
Sümer, Engin, Habibe Gören, Barış Barın, et al. 2026. “In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet”. Journal of Uludağ University Medical Faculty 52 (August). https://doi.org/10.32708/uutfd.1896815.
EndNote
Sümer E, Gören H, Barın B, Kosif Y, Başer Ö, Keleştemur M, Yavuz Y, Gül Z, Yılmaz B (August 1, 2026) In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet. Journal of Uludağ University Medical Faculty 52
IEEE
[1]E. Sümer et al., “In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet”, Journal of Uludağ University Medical Faculty, vol. 52, Aug. 2026, doi: 10.32708/uutfd.1896815.
ISNAD
Sümer, Engin - Gören, Habibe - Barın, Barış - Kosif, Yunus - Başer, Özge - Keleştemur, Miraç - Yavuz, Yavuz - Gül, Zülfiye - Yılmaz, Bayram. “In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet”. Journal of Uludağ University Medical Faculty 52 (August 1, 2026). https://doi.org/10.32708/uutfd.1896815.
JAMA
1.Sümer E, Gören H, Barın B, Kosif Y, Başer Ö, Keleştemur M, Yavuz Y, Gül Z, Yılmaz B. In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet. Journal of Uludağ University Medical Faculty. 2026;52. doi:10.32708/uutfd.1896815.
MLA
Sümer, Engin, et al. “In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet”. Journal of Uludağ University Medical Faculty, vol. 52, Aug. 2026, doi:10.32708/uutfd.1896815.
Vancouver
1.Engin Sümer, Habibe Gören, Barış Barın, Yunus Kosif, Özge Başer, Miraç Keleştemur, Yavuz Yavuz, Zülfiye Gül, Bayram Yılmaz. In Vivo Responses of Arcuate Tyrosine Hydroxylase (TH) Neurons to Hormonal Challenges Under Chronic High-Fat Diet. Journal of Uludağ University Medical Faculty. 2026 Aug. 1;52. doi:10.32708/uutfd.1896815

ISSN: 1300-414X, e-ISSN: 2645-9027

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