Cyanobacteria as a source
of bioactive compounds with
effects on obesity and
obesity-related co-morbidities

CYANOBESITY aims to develop novel
nutraceuticals that have the potential
to 
improve the quality of life for individuals

affected by obesity or related diseases.

Project Concept

The European ERA-NET MB project CYANOBESITY aims to develop novel nutraceuticals with effects on obesity and obesity-related co-morbidities in order to improve the quality of life of affected individuals. Nutraceuticals are regarded as “low hanging fruits” and normally defined as natural products from food resources with additional health effects.
In the proposed project, marine cyanobacterial strains of the culture collection from CIIMAR (LEGE CC) will be screened for beneficial properties towards obesity and obesity-related co-morbidities (obesity, fatty liver disease, diabetes, appetite and hyperlipidaemia) and the chemical structure of novel compounds will be elucidated. The molecular mechanism will be deciphered by applying an innovative biotechnological platform using chemical proteomics, analysing the interactions from oral administration to the blood stream, and with different target tissues in vitro. A proof of concept regarding the improvement of metabolism will be performed in a relevant physiological model. 

Objectives

- Screen cyanobacterial strains for beneficial properties towards obesity and obesity-related co-morbidities

- Isolate and elucidate the chemical structures of novel compounds responsible for observed bioactivities

- Characterize the biological properties of novel compounds: focus on the understanding of the underlying molecular mechanism and deciphering of molecular targets

Obesity, a global health hazard

Background

Obesity is a global health hazard associated with health problems such as hypertension, high cholesterol, type 2 diabetes, cardiovascular diseases, sleep apnea, respiratory problems (asthma), musculoskeletal diseases (arthritis) and some forms of cancer (Circulation 2007 116 39–48). In the last 20 years, the percentage of obesity has nearly doubled in many European countries, with more than 50% of the adult population being overweight (OECD, 2014). Over the years, many drugs have been proposed to treat or prevent obesity, however, during the long history of anti-obesity pharmacotherapy many drugs displayed a wide range of dangerous side-effects. An urgent demand for new anti-obesogenic compounds is present, and marine cyanobacteria promise to be an excellent source for natural-derived molecules and novel nutraceuticals.

Cyanobacteria are photosynthetic bacteria also known as blue-green algae that are widespread in aquatic ecosystems. Cyanobacteria are a prolific source of novel bioactive compounds and a wide range of bioactivities were observed from cyanobacterial natural products including for human diseases. The most famous example of a compound derived from cyanobacteria is brentuximab vedotin that is a FDA-approved anticancer drug for the clinical treatment of soft carcinoma (http://marinepharmacology.midwestern.edu/clinPipeline.htm).
Some strains of cyanobacteria are commercially available for consumption due to their beneficial properties to human health, e.g. Arthrospira, Nostoc and Aphanizomenon (Appl Microbiol Biotechnol 2004 65 635–648). Preclinical studies have been performed in various animal models and demonstrated that supplementation of the diet with Arthospira species, a traditional food in Central Africa, significantly ameliorated the hyperlipidemic profiles of high fat/high cholesterol diet, high fructose and high sucrose diets, and carbon tetrachloride-induced fatty livers in rats and mice, lowering hepatic cholesterol and triglyceride levels. CIIMAR hosts a cyanobacterial culture collection with strains mainly from the Portuguese Atlantic region (LEGE CC). The majority of the cyanobacterial strains of the collection were not explored yet for their potential bioactivities on the lipid metabolism.


Fighting obesity and related diseases with microalgae

Work Package

WP1

Biomass & Bioactive compounds

The WP1 will comprise the biomass production from cyanobacterial strains from the Blue
Biotechnology and Ecotoxicology Culture Collection (LEGE CC) of CIIMAR, and the chemical work related to the (i) production of (sub)fractions and the (ii) elucidation of chemical structure. Produced biomass will be extracted and fractionated, and forwarded for biological activity testing in WP2. 

WP2

Bioactivity

The specific objective of WP2 is to elucidate the effects of cyanobacterial derived fractions on obesity-related metabolic diseases (obesity, hyperlipidemia, fatty liver disease, diabetes). Analysis of biological activity is a central part of the project and will provide feedback for production of (sub)fractions (WP1) leading to isolated compounds.

WP3

MS platform & Mechanisms

The main objectives are to elucidate the target actions of those novel compounds and potential side effects. We will provide an integrated platform for the rapid characterization of bioactive compounds through their targeting profiles by chemical proteomics, and for elucidating the molecular networks responsible for specific phenotypes by quantitative proteomics. Proof of concept integrating obtained in vitro results will be done in the obesity mouse in vivo.

WP4

Management and Dissemination

The overall aims are to set-up a suitable management structure of the project that will ensure the overall management, conflict resolution and quality assurance.
A further goal is to disseminate the project aims and results to different stakeholder groups, in particular the scientific community, potential industrial collaboration partners and the general public.

Nutraceuticals from microalgae

Consortium

The consortium of the Cyanobacteria project consists of established experts with excellent competencies in complementary scientific and technological areas. The project involves a consortium of 4 countries (Portugal, Sweden, Germany and Iceland) and is co-funded in the framework of ERA MarineBiotech (www.marinebiotech.eu) by the following national funding agencies: Science and Technology Foundation (FCT, PT), Federal Ministry of Education and Research (BMBF, DE), Icelandic Centre of Research (RANNIS, IS) and Swedish Research Council (FORMAS, SE). 


CIIMAR

Project Leader

CIIMAR – Interdisciplinary Centre of Marine and Environmental Research – is a research and advanced training institution hosted by the University of Porto. Its mission is to develop exceptional-quality research, promote technological development and innovation and support public policies in the area of Marine and Environmental Sciences.

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University of Linkoping (Sweden)
Dep Clinical and Experimental Medicine,

Partner

Linköping University, LiU, conducts world-leading, boundary-crossing research in fields that include natural science, biomedicine, materials science, and IT. In the same spirit, the university offers many innovative educational programmes, frequently with a clear professional focus and leading to qualification as, for example, doctors, teachers, economists and engineers.

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Helmholtz Zentrum München
Institute of Diabetes and Obesity 

Partner

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, lung diseases and allergy. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle.

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ArcticMass

Partner

ArcticMass is based in Reykjavðk, Iceland. The employees of ArcticMass are highly experienced in bioanalysis and most of them are former members of the bioanalytical laboratory of deCODE genetics.
ArcticMass offers high quality bioanalytical services for the pharmaceutical industry, using analytical techniques like LC-MS/MS, UPLC-MS/MS, LC-Q-TOF, HPLC-FL and HPLC-UV. ArcticMass has a strong relationship with a high quality in vivo laboratory.

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University of Iceland
Faculty of Pharmaceutical Sciences

Partner

The Faculty of Pharmaceutical Sciences is an educational and research institution of international standing, which has close ties with Icelandic industry and society. The faculty is a vibrant and highly valued research and teaching unit; in fact it is one of the most productive of the University's Faculties.

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Contacts

CIIMAR | Interdisciplinary Centre of Marine and Environmental Research of the University of Porto
Edifício do Terminal de Cruzeiros do Porto de Leixões
Avenida General Norton de Matos, S/N
4450-208 Matosinhos | Portugal | Tel. (+351) 223 401 840
E-mail: cyanobesity@ciimar.up.pt
www.ciimar.up.pt 

Team

Ralph Urbatzka (coordinator),

CIIMAR
Email

Filipa Rosa

CIIMAR
Email

Tiago Ribeiro

CIIMAR
Email

Susana Cristobal

University of Linkoping
Email

Ana Carrasco

University of Linkoping
Email

Siegfried Ussar

Helmholtz Zentrum München
Email

Rene Hernandez Butista

Helmholtz Zentrum München
Email

Finnur Freyr Eiríksson

ArcticMass 
Email

Margrét Þorsteinsdóttir

University of Iceland
Email

Margarida Costa

University of Iceland
Email

This work is financed by national funds through FCT (Portugal), BMBG (Germany), Rannis (Iceland and Formas (Sweden), within the framework of the European ERA-NET Marine Biotechnology project CYANOBESITY.

More information about ERA-NET Marine Biotechnology and funded projects can be read here:
www.marinebiotech.eu