Nocarpiperazine A reduces lipid deposition and oxidative stress in Caenorhabditis elegans.

This study characterised Nocarpiperazine A (NPA), a novel Z-configured 2,5-diketopiperazine isolated from the marine-derived actinomycete Nocardiopsis sp. OUCMDZ-4937, and evaluated its anti-obesity effects using high-glucose diet-induced obese Caenorhabditis elegans. NPA dose-dependently lowered intracellular triglyceride content and lipid droplet deposition. Mechanistically, NPA accelerated fatty acid β-oxidation through upregulation of nhr-49 and cpt-2, while suppressing de novo lipid synthesis via inhibition of stearoyl-CoA desaturase genes (fat-5, fat-6 and fat-7). It also alleviated oxidative stress by enhancing superoxide dismutase and glutathione activities, reducing malondialdehyde levels, and activating antioxidant genes (sod-3 and gst-4). Notably, NPA also decreased the pharyngeal pumping rate in nematodes, suggesting a reduction in food intake as an auxiliary mechanism contributing to its lipid-lowering effects. Collectively, these findings indicate that NPA exerts multi-target anti-obesity activities, highlighting its potential as a natural lead compound for management of obesity and associated metabolic disorders.