Obesogens in a naturally obese animal: An experimental approach to assess the impact of marine pollutants on fat tissue function in seals

Lead Research Organisation: University of Abertay Dundee
Department Name: Sch of Science Engineering and Tech

Abstract

The ability of organisms to survive and thrive in a changing and increasingly exploited and polluted environment depends on appropriate regulation of energy balance. Growing evidence suggests that exposure to pollutants can alter how fat is stored and used in humans and in other animals. Recent research in humans suggests that many marine pollutants can interfere with the way fat tissue responds to hormonal signals. In particular, pollutants make it difficult to lose weight by switching on pathways that increase fat storage, and this could contribute to problems like diabetes and obesity. Large amounts of persistent organic pollutants (POPs) were made in the early part of the 20th century for use in high capacity electrical conductors and inks, insulators and plastics. Although many POPs are not made anymore because they are very toxic, they are extremely stable and remain in the environment for a long time, ending up in the sea from transport in air and water. Other pollutants, such as phthalates, which are important plasticisers, easily make their way into the sea in run off from urban areas and from marine litter. In particular, POPs do not break down very easily, accumulate in fat and become more concentrated as they are passed up the food chain, ending up in liver and fat. Seals are important top marine predators that have to build up a thick blubber layer while feeding at sea, and then use the fat as a metabolic fuel to keep them alive when they come ashore to breed, moult and rest. They have metabolic similarities to obese and diabetic patients. Their need to rely on fat for fuel and insulation makes them vulnerable to the effects of marine pollutants on the way fat tissue works. The higher the level of POPs in the blubber of seal pups, the lower their chance of survival. Fat tissue like blubber is important for storing fat, releasing it into the bloodstream for use by other parts of the body and producing fat-regulating hormones that control how much fat is stored or used. Recently, the genes of some fat-regulating hormones were shown to be switched on more in blubber of seals from polluted areas in the Baltic Sea than in clean areas in the Arctic, suggesting marine pollutants alter energy balance in seals. However, the mechanisms that control how fat tissue works in seals, and the way marine contaminants interfere with this control, are not well understood. If contaminants can prevent seals from releasing fat from blubber to give them fuel when they are fasting on land, they may have to use more of their protein from muscle tissue instead. This could put them at risk of starvation during moulting, breeding and development, even when they are fat. We will investigate whether pollutants alter fat storage and mobilisation in young grey seals, which are most at risk. We will take small blubber samples from live feeding and fasting seals, without harming them, and treat the blubber with pollutants and fat regulating hormones. We will measure levels of genes and hormones involved in energy balance, the ability of blubber to release fat, and its metabolic rate. By comparing these measures between treatments we will begin to find out how energy balance is normally regulated in seals, how it is altered by marine contaminants, and whether seals are more vulnerable during feeding or fasting. This will help predict the effects of pollutants on seal population size, by contributing a better understanding of how contaminants affect survival of young seals and change their energetic requirements. Because seals naturally experience extreme changes in fat mass, have metabolic similarities to diabetes and obesity, and eat fish, like people do, this work will also inform the likely impacts of POPs and phthalates on human fat regulation. This work has far reaching consequences for health and survivorship in seals and other animals, but also for the management of obesity, diabetes and related metabolic abnormalities in humans.

Planned Impact

The main beneficiaries of our work will be advisors and policy makers in marine protection and prevention of obesity. The outputs will ultimately benefit those with a duty to protect vulnerable marine ecosystems and preserve the marine environment against pollution under UN General Assembly resolution 67/70, and those who provide advice to such bodies e.g. the International Council for the Exploration of the Sea (ICES). This includes ICES Working Groups on Marine Mammal Ecology (WGMME) and Biological Effects on Contaminants (WGBEC). Our outputs will reach relevant national government departments and advisory bodies including the Special Committee on Seals (SCOS), the Department for Environment Food and Rural Affairs (DEFRA); Marine Scotland Policy and Planning; Natural England and Natural Resources Wales, and interest overseas agencies such as Department of Fisheries and Oceans (DFO), Canada. They will interest European (Convention for the protection of the marine environment of the North West Atlantic (OSPAR) commission) and global (ICES) intergovernmental agencies, who will be able to use the information to interpret seal population "biodiversity" indicators and "clean and safe" contaminant indicators of Good Environmental Status (GES) in the European Marine Framework Strategy Directive (MFSD). The public will benefit from more effective policy and environmental monitoring, which will facilitate Government's commitment to clean, healthy, safe, productive and biologically diverse oceans and seas. This will indirectly improve quality of life by ensuring sustainable management of marine resources, better policing of legacy and emerging contaminants in marine food webs and maintaining the natural capital of the seas.
Policy makers and advocacy groups targeting the obesity epidemic, particularly those with a duty to prevent and control non-communicable diseases under UN General Assembly resolution 66/2, including the World Health Organisation (WHO), will benefit. The European Association of the Study of Obesity (EASO), and its UK subsidiary, ASO, promote multidisciplinary approaches to obesity research and management, provide a discussion forum and aim to maximise uptake and public benefit of research. Through membership of ASO, we will ensure the outputs are available to EASO, the foremost European scientific and practice-based organisation of professionals in obesity prevention, with formal relations with WHO regional offices and membership of the World Obesity Federation (WOF). Information and advice arising from the project has the potential to influence policy and interventions that would benefit health care providers and advisory groups, such as the National Health Service (NHS), and the National Institute for Health and Care Excellence (NICE). End users, including the UK population, and groups with high dietary contaminant exposure risk will benefit from increased quality of life through advice on obesity prevention, which could have positive economic effects by alleviating strain on health care providers.
Impact through training includes development of technical skills used across disciplines and in public and private sectors. Timely training in media engagement and how science informs policy will have societal impact by increasing the effectiveness of communication by the project team, producing positive effects on public understanding of science and uptake of science into advice to government.
Schools, public outreach, and citizen science organisations will benefit from resources and information we produce and activities such as annual public lectures, visits to schools, participation in Bioblitz and national science events, such as Soapbox Science. Conservation organisations and groups advocating reduced use of plasticisers and other chemicals will find the project useful in identifying where pressure may be needed on Government to address issues of legacy and emerging contaminants on ecosystem and human health.

Publications

10 25 50
 
Description Physiological Society travel grant
Amount £700 (GBP)
Organisation Physiological Society 
Sector Learned Society
Country United Kingdom
Start 12/2015 
End 12/2015
 
Title Explant development in seals 
Description We have developed and refined the use of adipose tissue explants from seals. 
Type Of Material Biological samples 
Year Produced 2015 
Provided To Others? Yes  
Impact Use of adipose tissue explants replaces animals in whole animal research to investigate local regulation and endocrine disruption of fat tissue. It opens up possibilities for a more experimental approach in this aspect of comparative physiology. 
 
Title Validation of planar optodes in closed system respirometry of adipose tissue explants 
Description This method uses oxygen sensitive planar optodes to monitor oxygen levels in samples. It has been used in ecological monitoring of small organisms and bacterial growth, but to the best of our knowledge has not been used before to investigate oxygen use of explants in medium term culture experiments. We have investigated whether we can monitor oxygen use in fat tissue explants from seals using this technology and how best to apply the technology in this context, with a view to monitor tissue viability and align with other markers of health and function. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact None yet 
 
Description Collaboration with Gauthier Eppe's lab at University de Liege 
Organisation University of Liege
Department Department of Chemistry
Country Belgium 
Sector Academic/University 
PI Contribution Our team member Dr Kelly Robinson went to Liege in summer 2015 for 5 weeks and was trained in Gauthier Eppe's lab in the methods to extract persistent organic contaminants from blubber tissue. These data will be used by us in three ways: as covariates to explain changes in metabolic activity and gene expression of explants; to quantify changes in POPs over time by comparing values with those from the same population in previous years; and to investigate associations between POPs and metabolic characteristics.
Collaborator Contribution Gauthier's team trained Kelly in the sample extraction methods and subsequently ran the samples to identify and quantify the congeners present.
Impact This partnership is mutlidisciplinary. The team at Abertay and SMRU are physiologists interested in the toxicological and metabolic effects of contaminants and their ecological consequences. The team in Liege are environmental chemists interested in quantifying POPs in a variety of matrices to monitor their levels in the environment.
Start Year 2015
 
Description Contaminant analysis collaboration with Dr C Debier 
Organisation Catholic University of Louvain
Country Belgium 
Sector Academic/University 
PI Contribution Discussion of use of explants as an appropriate in vitro model in seals and the potential use in agricultural animals such as pigs. Discussion of methodology for explant preparation and use of closed system respirometry method for monitoring tissue health and responses.
Collaborator Contribution Arrangement of contaminant analysis by additional Belgian partners to occur later in the year; advice on best practice for sample collection and storage for sample contaminant analysis; advice on range of contaminants to analyse; sharing ideas on use of tissue viability markers; sharing methodological development and technical issues for possible use of tissue slices and isolated adipocytes.
Impact Strategy for sample analysis; Invited seminar about obesogens and current project at Universite Catholique de Louvain
Start Year 2014
 
Description Blog for BBC Autumnwatch: Grey seals pups are having to deal with chemicals produced as a result of industry 10.12.2017 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I wrote a blog for BBC Autumnwatch about our work to understand how seals energy balance is altered by pollutants. This reached followers of Autumnwatch blogs and was timed to coincide with Blue Planet 2 to reach a much wider BBC audience. It reached @PHATSAbertay followers on Twitter (~700), followers of the BBC Autumnwatch account and subsequent retweets.
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/blogs/natureuk/entries/4399bf8f-85d9-4424-921f-aefa531c9723
 
Description Blog for The female Scientist: How do seals regulate their fat stores? 30. 8.2017 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I wrote a contribution to the Female Scientist about our project including the contrast with humans in fat regulation, how we can investigate fat regulation in seals, the challenges involved, and the explant approach we use. This has been tweeted by myself (~700 followers) and by @ScientistFemale which has >3000 followers. An author has also contacted me about writing a book on grey seals and wanted to more about this project as a result of the Blog.
Year(s) Of Engagement Activity 2017
URL https://thefemalescientist.com/research/kimberley-bennett/1477/how-do-seals-regulate-their-fat-store...
 
Description Cafe Science Dundee: How is pollution affecting Scottish seals ? 9th October 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact I gave a talk to a capacity room (I believe ~70 people), using props but no powerpoint, on pollution effects on seals, including some of our evidence from this project that glucose uptake is influenced. This led to a lively question and answer session about the role of pollution and what we can do to minimise it and mitigate its effects both personally and more widely. Several people came to me afterwards to discuss individual points, as well as career options, the value of chemistry and engineering in the solutions etc.
Year(s) Of Engagement Activity 2017
URL https://www.skiddle.com/whats-on/Dundee/Avery-And-Co/Caf-Science-Dundee-How-is-Pollution-affecting-S...
 
Description Dundee University Museums Collection public talk series: Fitness and fatness in Seals and Humans. D'Arcy Thompson Zoology Museum, Dundee, UK, Dec 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact KB gave a talk at Dundee University Museums Collection in their public talk series, entitled Fitness and fatness in Seals and Humans. We explored why being fat is so important to seals, what we know about how they regulate fatness compared with humans, how pollutants can influence body fat control in both seals and humans and the potential consequences for human and animal health. The talk initiated lots of questions about general seal physiology, comparisons with human obesity and issues related to avoiding contaminants in food. It also led to invites to give additional talks elsewhere in the local area
Year(s) Of Engagement Activity 2016
URL https://www.abertay.ac.uk/research/research-projects/phats/news/name,33241,en.php
 
Description Environmental Analytical Chemistry symposium, Dundee 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact This was a talk at the Royal Society sponsored Scottish Environmental Analytical Chemistry meeting. Approximately 50 people attended, who were primarily environmental chemists and representatives from Marine Scotland. This meeting instigated a number of useful collaborations, including with groups who can analyse a wider range of POPs and also trace metal toxins.
Year(s) Of Engagement Activity 2016
URL https://www.abertay.ac.uk/research/research-projects/phats/news/name,33242,en.php
 
Description Guest seminar: Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee. April 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Talk entitled Seals as models for obesity: insights and challenges from the champions of fat deposition. Intended to reach those working in medical science, both as researchers and clinicians. ~30 people attended and this initiated interesting discussions with people engaged in human diabetes and obesity research, and instigated conversations about future collaborations. Ongoing contact and fruitful discussions with a number of researchers (eg Calum Sutherland) has been maintained.
Year(s) Of Engagement Activity 2016
 
Description Invited Seminar Speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact This invited lunchtime seminar to the University of Brunel postgraduate researchers led to increased awareness of this study among environmental scientists with interests in the impact of contaminants on human health. This gorup would not necessarily be aware of research in our field so it was a good opportunity to inform peer groups of the aims and objectives of the study.
Year(s) Of Engagement Activity 2015
 
Description Invited plenary talk at UK and Ireland chapter for Society of Marine Mammalogy: Seals as models for obesity: insights and challenges from champions of fat deposition Jan 19th 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact I was invited to give a talk to the students at the UK IRSC. ~50 students attended. After the talk several students asked for more information and asked about opportunities to participate in the work.
Year(s) Of Engagement Activity 2017
URL https://synergy.st-andrews.ac.uk/ukrsc/files/2016/09/UKIRSC-2017-TIMETABLE-and-ABSTRACT-BOOKLET.pdf
 
Description Invited talk at Perth Natural Sciences Society Curious Minds series: The Remarkable Physiology of the Seal, AK Bell library, Perth. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact I gave an hour talk on the physiology of seals in relation to fasting, energy balance and diving to ~60 people drawn from the local Natural Science Society. There was an extensive question and answer session afterwards and various members of the audience came to me with comments afterwards about ' I had no idea that....'. The orgaiser afterwards has approached me about being involved in further activities with this group.
Year(s) Of Engagement Activity 2017
URL https://www.perthcity.co.uk/event/curious-minds-remarkable-physiology-seal/
 
Description Invited talk: 2nd International Conference on Clinical Sciences and Drug Discovery. University of Dundee. July 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk: 2nd International Conference on Clinical Sciences and Drug Discovery. This was a talk to a group of scientists working in clinical science and industry. It initiated many questions and conversations about the need for next generation approaches. We made key international contacts for future work.
Year(s) Of Engagement Activity 2016
URL https://www.abertay.ac.uk/research/research-projects/phats/news/name,31429,en.php
 
Description Kelly Robinson's Blog about our project, including the field and lab elements 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Dr Kelly Robinson, the postdoctoral RA on this grant, write a regular blog talking about the work we are doing for this project. It routinely reaches her regular audience of ~50 people, and traffic to the site is increased by tweets from @PHATSAbertay (~700 followers) @SteeleySeabirder (~7500 followers), the warden on the Isle of May, and @SMRU_ (~1600) followers.
Year(s) Of Engagement Activity 2017
URL https://kellyrobinsonscience.wordpress.com/author/kjrscience/
 
Description Oral presentation: 22nd Biennial conference on the biology of marine mammals, Halifax, Nova Scotia. October 22nd-27th 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Kelly Robinson delivered a talk on our work: An explant approach to understand adipose tissue function; metabolic profiles of blubber tissue differs between tissue depth, cell culture conditions and energetic state to an audience of marine mammal biologists and conservation workers, policy makers, students and academics. ~150 people attended the talk and asked questions immediately afterwards about the contaminant effects reported. Later on, we were approached by other academics for further information and expressing an interest in collaborative work. This has been followed up by opportunities to collaborate and circulation of grant calls of interest in the USA.
Year(s) Of Engagement Activity 2017
URL http://www.smmconference.org/scientificprogram
 
Description Poster presentation: 22nd Biennial conference on the Biology of Marine Mammals, Halifax, Nova Scotia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster entitled: Accurate and precise measures of blood glucose from fasted grey seal pups using a hand held glucometer: implications for rapid health assessment and glucose tolerance tests in the field. This poster was intended to present our work on trying to get rapid glucose measurements from seals without the contingent problems of sample processing and storage that can alter the results. From our point of view, this method would avid several weeks' of lab work and save storage space for plasma. ~15 people from different international organisations sought me out at the poster event to find out more. A great deal of interest in the development of a rapid and user friendly tool that requires minimum blood sample was shown by people involved in rehabilitation and in conservation of endangered species - an audience I had not thought would be the primary interest group. This had led to fruitful conversations about the development of this method for purposes outside research.
Year(s) Of Engagement Activity 2017
URL http://www.smmconference.org/scientificprogram
 
Description Public lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Approximately 100 people attended this lecture at St Abbs Marine Station which resulted in many questions and discussion afterwards.
Year(s) Of Engagement Activity 2018
 
Description SEB main meeting July 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Kimberley Bennett gave a pecha kucha and poster entitled Circulating polychlorinated biphenyls are associated with altered plasma adiponectin levels in grey seal pups. She presented preliminary data on an association between adiponectin and blood POP levels in a small sample of grey seal pups. This presentation generated interest from scientists from the US and Australia who had not previously encountered the concept that pollutants can modify energy balance in wildlife. It resulted in encouragement by the conservation physioogy session organisers to present our experimental findings at the next SEB meeting in July of 2017.
Year(s) Of Engagement Activity 2016
URL https://www.sebiology.org/docs/default-source/Event-documents/cross-disciplinary-abstracts.pdf
 
Description Scottish Natural Heritage 'seals weekend', Isle of May, Firth of Forth, UK, October 2016 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We participated in a 2 day weekend event showcasing how seals are able to gain weight and lose it quickly, require fat for survival and are 'canaries in the mine' for contaminant effects on energy balance regulation. We had discussions with members of the public, showed them the seal colony, answered lots of questions about their life history, general seal biology and ecology, the importance of long terms data sets, seal physiology and anatomy and the research we are doing on this project. We took along fliers, a seal skeleton, images to show on a loop, and participated in the show and tell where members of the public used a spotting scope to see newly arrived seals on the colony. We also gave a talk and fielded questions on the boat on the way to and from the island. This event helped us maintain our working relationship with the crew of the May Princess, who help with our logistics during our field season, and with SNH who provide the permits for the work on the NNR, as well as discuss our project with members of the public.
Year(s) Of Engagement Activity 2016
URL https://www.abertay.ac.uk/research/research-projects/phats/news/name,33235,en.php
 
Description Scottish Natural Heritage seals weekend, Isle of May, Firth of Forth, October 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I went out to the Isle of May on board the May Princess as 'tour guide and expert' for the SNH's annual seals weekend, when the first animals have arrived on the island to breed in early October. I gave a talk on the boat on the way out about seal biology and our project. On the island I gave a talk about what life is like on the island for a seal researcher and gave more information on the project. Finally, I was stationed at one of the observation sites to field questions about the seals and their biology. About 50 people attended, some of whom were masters' students at St Andrews University. I was asked lots of questions both on the island and on the return trip.
Year(s) Of Engagement Activity 2017
URL https://www.snhpresscentre.com/news/seals-take-the-stage-on-the-isle-of-may