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Identification of Cyanobacterial Strains with Potential for the Treatment of Obesity-Related Co-Morbidities by Bioactivity, Toxicity Evaluation and Metabolite Profiling

1
Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland
2
Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Avenida General Norton de Matos, s/n, 4450-208 Matosinhos, Portugal
3
RG Adipocyte and Metabolism, Institute for Diabetes and Obesity, Helmholtz Center Munich, 85764 Neuherberg, Germany
4
INBB, Consorzio Interuniversitario Biosistemi e Biostrutture, 00136 Rome, Italy
5
ArcticMass, Sturlugata 8, 101 Reykjavik, Iceland
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(5), 280; https://doi.org/10.3390/md17050280
Received: 13 April 2019 / Revised: 3 May 2019 / Accepted: 7 May 2019 / Published: 10 May 2019
(This article belongs to the Special Issue Marine Natural Products and Obesity)
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Abstract

Obesity is a complex disease resulting in several metabolic co-morbidities and is increasing at epidemic rates. The marine environment is an interesting resource of novel compounds and in particular cyanobacteria are well known for their capacity to produce novel secondary metabolites. In this work, we explored the potential of cyanobacteria for the production of compounds with relevant activities towards metabolic diseases using a blend of target-based, phenotypic and zebrafish assays as whole small animal models. A total of 46 cyanobacterial strains were grown and biomass fractionated, yielding in total 263 fractions. Bioactivities related to metabolic function were tested in different in vitro and in vivo models. Studying adipogenic and thermogenic gene expression in brown adipocytes, lipid metabolism and glucose uptake in hepatocytes, as well as lipid metabolism in zebrafish larvae, we identified 66 (25%) active fractions. This together with metabolite profiling and the evaluation of toxicity allowed the identification of 18 (7%) fractions with promising bioactivity towards different aspects of metabolic disease. Among those, we identified several known compounds, such as eryloside T, leptosin F, pheophorbide A, phaeophytin A, chlorophyll A, present as minor peaks. Those compounds were previously not described to have bioactivities in metabolic regulation, and both known or unknown compounds could be responsible for such effects. In summary, we find that cyanobacteria hold a huge repertoire of molecules with specific bioactivities towards metabolic diseases, which needs to be explored in the future. View Full-Text
Keywords: anti-obesity drugs; metabolite profiling; zebrafish Nile red fat metabolism assay; uncoupling protein 1; bioactivity screening; diabetes; fatty liver disease; cyanobacteria anti-obesity drugs; metabolite profiling; zebrafish Nile red fat metabolism assay; uncoupling protein 1; bioactivity screening; diabetes; fatty liver disease; cyanobacteria
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Costa, M.; Rosa, F.; Ribeiro, T.; Hernandez-Bautista, R.; Bonaldo, M.; Gonçalves Silva, N.; Eiríksson, F.; Thorsteinsdóttir, M.; Ussar, S.; Urbatzka, R. Identification of Cyanobacterial Strains with Potential for the Treatment of Obesity-Related Co-Morbidities by Bioactivity, Toxicity Evaluation and Metabolite Profiling. Mar. Drugs 2019, 17, 280.

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