TDK conference 2024

Gold nanoparticles (AuNPs) have numerous beneficial properties, enabling their use as intracellular drug carriers, while their potential for diagnostic and therapeutic applications is increasingly being recognized. Within the central nervous system, the hypothalamus is the first area where nanoparticles interact with the brain, as this neuroendocrine centre is particularly sensitive to factors in the systemic circulation due to its function and localisation. AgRP and POMC neurons within the hypothalamus are integral components of the melanocortin system, which influences metabolic function in the whole body by maintaining homeostasis. The dynamic adaptation of mitochondrial function is essential in this regulatory process. Therefore, this study aims to investigate how gold nanoparticles affect the mitochondrial activity of POMC neurons in relation to concentration and exposure time under in vitro conditions.

For this purpose, we used immortalized POMC cell cultures derived from mice. The cells were treated with gold nanoparticles (Sigma, product no. 741965; 20 nm, spherical) at three different concentrations (6.54x10⁴, 6.54x10⁷, and 6.54x10¹⁰ particles/ml), with incubation periods of 1, 4, 15, and 24 hours. Mitochondrial activity was measured using a Seahorse XFp Analyzer (Agilent Technologies, California, USA), which recorded oxygen consumption rate (OCR) parameters.

Our results revealed significant variations in mitochondrial activity depending on nanoparticle concentration and incubation duration. While no significant differences were observed in the maximal respiratory capacity compared to the control group, a noteable decrease in ATP production was detected across most experimental conditions.

Based on these findings, we hypothesise that gold nanoparticles generally inhibit mitochondrial activity in POMC cells, potentially altering hypothalamic homeostatic regulation. In vivo, this could disrupt energy balance by decreasing satiety, increasing hunger, and activating pathways that stimulate food intake. However, further research is required to confirm these mechanisms and their broader implications.