Poster 49th Nutrition Society of Australia Annual Scientific Meeting 2025

High-Fat Diet-Induced Alterations in Redox Balance and Leptin Regulation in in vivo Models: A systematic review and meta-analysis (130108)

Elaheh Heshmati 1 2 , Zinat Mohammadpour 3 , Amanda Page 1 2
  1. University of Adelaide, Adelaide, SA, Australia
  2. Vagal Afferent Research Group, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
  3. College of Medicine and Dentistry, James Cook University, Cairns, Cairns, QLD, Australia

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.

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