The effect of an experimental amino acid-based sugar substitute on lipid accumulation in Caenorhabditis elegans: a pathophysiological and biophysical study

Abstract

Background. The problem of excessive sugar consumption is one of the key issues in modern dietetics, acting as a risk factor for the development of obesity, metabolic syndrome, and type 2 diabetes [1, 2]. In this regard, there remains a high demand for safe and effective sugar substitutes that would not only possess the desired organoleptic properties but also would not contribute to metabolic disruption [3].

Aim. Evaluation of the effect of an experimental sugar substitute based on a combination of amino acids and a prebiotic on neutral lipid metabolism in Caenorhabditis elegans, as well as to verify its metabolic safety during long-term exposure in comparison with sucrose, stevia, and metformin.

Methods. Nematodes were cultured in the presence of the tested compounds for 5 days, followed by fluorescent staining of lipid droplets using the BODIPY 493/503 dye. Quantitative assessment of fluorescence intensity, reflecting the volume of accumulated lipids, was performed using microscopy and subsequent image processing employing a specially developed pipeline in the Matlab and CellProfiler environments.

Results. It was shown that the developed sugar substitute significantly reduces lipid accumulation in the organism of C. elegans compared to sucrose. The most pronounced effect was observed at a concentration of 0.5 mg/mL, where the mean fluorescence intensity was 0.2339 versus 0.5271 for sucrose (p < 0.001). The combination of the sugar substitute (0.5 mg/mL) with metformin (10 µM) demonstrated a synergistic effect, reducing the lipid accumulation index to 0.1114, which is more than 5 times lower than in the group that consumed sucrose (1 mg/mL).

Conclusion. The new sugar substitute has a pronounced potential in the prevention of obesity, being not inferior in efficacy to stevia and exhibiting synergism with metformin. The obtained data justify its further study as a functional food ingredient and in metabolic pathophysiology.