Neuroscience offers important insights into the pathogenesis and treatment of obesity by investigating neural circuits underpinning appetite and feeding. Gamma-aminobutyric acid (GABA), one of the most abundant neurotransmitters in the brain, and its associated receptors represent an array of pharmacologically targetable mediators of appetite signalling. Targeting the GABAergic system is therefore an increasingly investigated approach to obesity treatment. However, the many GABAergic projections that control feeding have yet to be collectively analysed. This review provides a comprehensive analysis of the relationship between GABAergic signalling and appetite by examining both foundational studies and the results of newly emerging chemogenetic/optogenetic experiments. A current snapshot of these efforts to map GABAergic projections influencing appetite is provided, and potential avenues for further investigation are provided.

There is accumulating evidence that an obesogenic Western diet causes neuroinflammatory damage to the brain, which then promotes further appetitive behaviour. Neuroinflammation has been extensively studied by analysing the translocator protein of 18 kDa (TSPO), a protein that is upregulated in the inflamed brain following a damaging stimulus. As a result, there is a rich supply of TSPO-specific agonists, antagonists and positron emission tomography ligands. One TSPO ligand, etifoxine, is also currently used clinically for the treatment of anxiety with a minimal side-effect profile. Despite the neuroinflammatory pathogenesis of diet-induced obesity, and the translational potential of targeting TSPO, there is sparse literature characterizing the effect of TSPO on appetite. Therefore, in this review, the influence of TSPO on appetite is discussed. Three putative mechanisms for TSPO's appetite-modulatory effect are then characterized: the TSPO–allopregnanolone–GABA _A R signalling axis, glucosensing in tanycytes and association with the synaptic protein RIM-BP1. We highlight that, in addition to its plethora of functions, TSPO is a regulator of appetite. This review ultimately suggests that the appetite-modulating function of TSPO should be further explored due to its potential therapeutic promise.

Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes in non-anemic, iron-deficient individuals is limited and conflicting. Methods: This retrospective cohort study utilized the multi-institutional TriNetX database to examine the 5-year outcomes of iron therapy in adult women with stage 3 CKD, normal hemoglobin (≥12 g/dL), normal mean corpuscular volume (MCV), and low serum ferritin (<100 ng/mL). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, progression to advanced CKD (estimated glomerular filtration rate ≤30 mL/min/1.73 m²), and gastrointestinal (GI) bleeding. Results: We identified 53,769 eligible non-anemic patients with stage 3 CKD, low serum ferritin levels, and normal MCV. Propensity score matching (1:1) was conducted on demographic variables to compare iron-treated (n = 6638) and untreated (n = 6638) cohorts. Over the 5-year follow-up, iron therapy in non-anemic females with stage 3 CKD, low ferritin levels, and iron supplementation was significantly associated with increased risks of MACE, AKI, pneumonia, CKD progression, and GI bleeding (log-rank p < 0.0001). No significant difference in all-cause mortality was observed. Data on transferrin saturation and the dosage of iron supplementation were unavailable. Conclusions: In non-anemic women with stage 3 CKD and low ferritin levels, iron supplementation was linked to increased MACE, renal, and pneumonia risks without evident survival benefits. These findings suggest that iron therapy in this group of patients may not confer cardiovascular benefit and may pose risks.