Inhibition of Intestinal Lipid Absorption by Cyanobacterial Strains in Zebrafish Larvae

Obesity is a complex metabolic disease, which is increasing worldwide. The reduction of dietary lipid intake is considered an interesting pathway to reduce fat absorption and to affect the chronic energy imbalance. In this study, zebrafish larvae were used to analyze effects of cyanobacteria on intestinal lipid absorption in vivo. In total, 263 fractions of a cyanobacterial library were screened for PED6 activity, a fluorescent reporter of intestinal lipases, and 11 fractions reduced PED6 activity > 30%. Toxicity was not observed for those fractions, considering mortality, malformations or digestive physiology (protease inhibition). Intestinal long-chain fatty acid uptake (C16) was reduced, but not short-chain fatty acid uptake (C5). Alteration of lipid classes by high-performance thin-layer chromatography (HPTLC) or lipid processing by fluorescent HPTLC was analyzed, and 2 fractions significantly reduced the whole-body triglyceride level. Bioactivity-guided feature-based molecular networking of LC-MS/MS data identified 14 significant bioactive mass peaks (p < 0.01, correlation > 0.95), which consisted of 3 known putative and 11 unknown compounds. All putatively identified compounds were known to be involved in lipid metabolism and obesity. Summarizing, some cyanobacterial strains repressed intestinal lipid absorption without any signs of toxicity and could be developed in the future as nutraceuticals to combat obesity.