Heshmati, E., Mohammadpour, Z., and Page, A. (2026) High-fat diet-induced alterations in redox balance and leptin regulation in in vivo models: a systematic review and meta-analysis. In: Proceedings of the Nutrition Society (85) E220. From: 49th Annual Scientific Meeting of the Nutrition Society of Australia, 03-05 December 2025, Gold Coast, QLD, Australia.

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Abstract

Leptin, an appetite-suppressing hormone, plays a pivotal role in the regulation of energy homeostasis(1). Obesity is characterised by elevated circulating leptin levels but paradoxically impaired anorexigenic leptin signalling(2,3). This systematic review aimed to provide comprehensive insights into the association between redox imbalance induced by a high-fat diet (HFD) and the neuronal leptin signalling dysfunction. Five electronic databases (PubMed, Scopus, Embase, Emcare and Web of Science) were systematically searched to identify studies reporting the effect of HFD interventions on redox balance in the nervous system, focusing on leptin-driven neural mechanisms of energy homeostasis. Twenty-nine articles were identified for the systematic review, with 14 eligible for meta-analysis. The review demonstrated that HFD interventions led to increased oxidative stress, even after short-term exposure, and/or endoplasmic reticulum (ER) stress in neural tissues. Meta-analysis revealed that HFD significantly increased circulating leptin levels and oxidative damage, as indicated by elevated malondialdehyde (MDA), and impaired antioxidant defences, reflected by decreased glutathione (GSH) and superoxide dismutase (SOD), compared to controls. In addition, elevated leptin following HFD was associated with upregulation of the negative regulators of leptin signalling, including suppressor of cytokine signalling 3 (SOCS3), protein tyrosine phosphatase-1B (PTP1B), as well as decreased phosphatidylinositol 3 kinase (PI3K), and elevated phosphorylated AMP-activated protein kinase (AMPK), collectively indicating disrupted leptin signalling pathways. Additionally, HFD-induced peroxisome proliferation in hypothalamic neurons suggest moderate levels of reactive oxygen species (ROS) may fine-tune leptin sensitivity, while excessive ROS generation contributes to leptin resistance(4,5). These findings highlight the crucial interplay between redox homeostasis and leptin signalling in diet-induced obesity. However, the role of redox imbalance in modulating leptin signalling within the peripheral nervous system remains poorly understood and requires further investigation.

Item ID:	93852
Item Type:	Conference Item (Abstract / Summary)
ISSN:	1475-2719
Copyright Information:	© The Author(s), 2026. Published by Cambridge University Press on behalf of The Nutrition Society. Issue OCE2
Date Deposited:	31 Aug 2026 04:15
FoR Codes:	42 HEALTH SCIENCES > 4299 Other health sciences > 429999 Other health sciences not elsewhere classified @ 100%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200199 Clinical health not elsewhere classified @ 100%
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