Obesogens are man-made chemicals present in the food chain and water supply that can alter appetite and the way that the body processes fat, making fat gain much more likely and fat loss much more difficult. They can also make fat tissue more ‘inflammatory’ so that it is less healthy.
You can find out more about the background to our project and what it involves here.
What is an obesogen?
Why is obesity such a problem?
Obesity is the accumulation of fat to a point where it poses a significant health risk. Obesity is one of the fastest growing non communicable diseases. It affects about a quarter to a third of all adults in most populations, and childhood obesity is also on the increase. Being overweight or obese increases the risk of a wide range of complications such as diabetes, cardiovascular problems and certain cancers. It imposes a large financial burden at the state level in terms of health care provision and loss of earnings and productivity as a result of the health issues it creates. It can result in a range of physical, emotional and financial costs on a personal level. Despite large amounts of investment and efforts to curtail the increase in obesity, the problem persists in most sectors of society.
How do obesogens work?
In fat cells, obesogens can switch on a master energy-sensing switch called PPAR gamma. PPAR gamma then activates pathways that make fat cells divide and multiply and accumulate fat. Obesogens also turn on other cellular switches that activate pathways involved in inflammation. Other mechanisms also exist. For example, obesogens can act in the brain to increase appetite or preference for fatty foods, and there is also some evidence that fat absorption in the gut may be increased by obesogenic chemical effects on the microbiome: less ‘good bacteria’ can predispose people to gain fat.
Where do obesogens come from?
Many different chemicals seem to have obesogenic effects in humans. We are focussing on a group of chemicals called persistent organic pollutants, or POPs. POPs are not ‘organic’ in the sense of organic farming. They are called ‘organic’ because they contain carbon. The POPs that have most closely been linked to obesity and diabetes are some of the polychlorinated biphenyls (PCBs) and polybrominated diethyl ethers (PBDEs).
PCBs were produced widely in the 1940s through to the 1970s because they are very chemically and thermally stable. That made them very useful as capacitors and coolants, and PCBs were used in a huge range of industrial processes. They were released into the environment in the air and water. Since the 1970s, when the highly toxic effects of many PCBs were recognised, their production has become very tightly regulated and has almost completely ceased in most places. More recently PBDEs have been used as flame retardants.
Other obesogens, such as phthalates and TBTs, are less persistent because they are more easily broken down. Phthalates are water soluble and are used as plasticisers, so they are present in many food storage containers, cooking utensils and medical plasticware. Tri-butyl tins (TBTs), which are used as antifoulants on boats, have obesogenic effects, as well as their more well-known effects on reproductive health in aquatic animals. Some scientists have found that emulsifiers in our food can have obesogenic effects by altering the make-up of the gut microbiome.
As you can see its quite difficult to avoid being exposed to obesogens, and the list of obesogenic chemicals seems to be growing.
Why are POPs such a problem?
The properties that made POPs so useful have created a big problem because they are very resistant to chemical, temperature or biological breakdown which means they persist in the environment for a long time. They are also easily transported in air and water and are present in every type of habitat, even in areas they were never produced and are usually considered pristine, such as the Arctic and Antarctica. POPs are very fat soluble and so easily cross biological membranes. From soil and water they can get into the food chain where they accumulate in the fatty cells of animals. The further up the food chain, the more they become magnified so that animals at the top of the food chain have the highest levels. Fatty tissues, such as fat, liver and brain in particular, contain the most, but POPs are present in the blood stream and mother’s milk.
Why study seals?
Seals are notoriously fat. If you see a seal lazing about on a rocky outcrop or a beach you might think it’s no wonder! But we have to remember that the lifestyle of seals is fraught with constant physiological challenges. Seals are air breathing mammals that make a living under water in the cold, deep dark ocean, but need to come to the surface to breathe. This creates a range of problems that they need to overcome. They need to be able to insulate themselves against the cold, make sure they can find their way underwater in the dark, avoid nitrogen accumulation in the blood and tissues that would otherwise cause the bends, and maintain a good oxygen supply or survive without it.
Seals come ashore to rest, breed and moult. While they are on land they are away from their food source, and so they need to fast, which means voluntarily going without any food (and in this case water too).
Having a thick layer of fat under the skin, called blubber, really helps them fast and stay warm. Blubber is five times more effective as an insulator than air. So blubber prevents the loss of body heat to the cold water.
Even though it’s much heavier than fur, blubber doesn’t get wet because it’s on the inside, and its weight doesn’t matter when the animals are in the water because the water itself provides a buoyant force. Since fat is lighter than water, animals with a thicker blubber layer are more likely to float, really useful if you want to get to the surface quickly after a dive!
Fat is also great as a metabolic fuel store. You get about twice as many calories from ‘burning’ 1g of fat than you do from the same weight of either sugar (carbohydrate) or amino acids, the building blocks of protein. Fat contains very little water, unlike the storage form of sugar, called glycogen. That means fat is a highly efficient fuel store that you can carry round with you. If you tried to store the same amount of energy as liver glycogen, your liver would be so big it would be impossible to move around.
So seals effectively have an internal multi-purpose fuel store and duvet that keeps them warm and supplied with enough energy to keep them going even when they haven’t had a meal in a while. And when we say ‘a while’, grey seals can fast for up to 50 days without any sign of starvation – the process that kicks in when fat stores have run so low that the body has to start using protein as fuel instead. Starvation is bad because it quickly irreversibly damages muscle tissue and compromises tissue structure and function.
Seals are very heavily reliant on fat as a metabolic fuel. Whereas humans rely on a mix of fat and carbohydrates to meet most of our energetic needs, seals have almost no carbohydrate in their diet and rely almost exclusively on fat. Because their metabolism is so finely tuned to burn fat, they are very vulnerable to any processes that target or disrupt fat metabolism.
Why are obesogens a problem for seals?
Being fat is great for seals. The survival of pups in their first year is closely linked with how fat they were when they weaned. Females that are fatter can produce bigger, fatter pups. Its therefore better for adults to be fat too.
So does that mean that obesogens might be a good thing for these animals? Not really. The problem of being fat is that many obesogenic chemicals are fat soluble. They accumulate in fat tissue and magnify up the food chain. Seals are top predators, which means they get the highest dose from their food and the levels build up in their fat and liver, potentially affecting how the fat tissue works. Although they need to be very efficient at laying down fat to make sure they have a good layer of insulation and a metabolic fuel store, the fat is no good to them if they can’t mobilise it to keep them going when food is scarce or when they are fasting. Obesogenic chemicals may inhibit this process making it difficult for a fat animal to meet its energetic needs.
Why are seals useful in understanding obesity?
The famous physiologist, August Krogh, said that for every biological phenomenon there is an animal ideally suited for its study. If we want to understand fat deposition and mobilisation, look no further. Seals are extremely good at laying down fat: grey seal pups triple their body mass within 15-21 days of birth, and almost all the weight gain is from fat. That’s a phenomenal capacity for rapid fat deposition! Pups can be as much as 45% fat at weaning: a human with that body fat content would have serious health problems. If we can understand better how they lay down fat so fast, store fat almost exclusively under their skin (which is thought to be a ‘safer’ place to store fat than around internal organs) and avoid inflammation, we will have a much better insight into how humans could avoid the complications associated with obesity.
Similarly, seals can lose fat very rapidly without an increase in appetite. Female grey seals lose about 40% of their body mass, almost entirely from blubber, as they fast while feeding their pups. How do they mobilise their fat reserves so quickly and effectively while avoiding being hungry?
What does our project involve?
We are investigating how seals’ fat tissue normally responds to the hormones that typically regulate fat – leptin, cortisol and thyroid hormones. We then find out whether POPs alter this regulation. The way we do this is to take a small biopsy of fat tissue from seals that are either fattening up or using their fat during fasting.
In the lab we divide the biopsy into tiny pieces called explants. We expose the explants to hormones, POPs or both and compare their responses to an untreated ‘control’ piece of fat. We are measuring how much the signalling pathways involved in fat metabolism are turned on or off, and how much the cells use glucose and fats. This will help us predict the ecological effects of obesogens on seals, and the health consequences for humans.