Research grant

Brown fat: men versus women

Brown fat cells burn fat. How do we activate brown fat as a treatment for obesity? That’s what Alba Sabaté Pérez is going to investigate, thanks to the NWO ENW-XS grant she recently received. Her starting point: differences between men and women.

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Alba Sabaté Pérez

Brown fat is the counterpart of – the much better-known – white fat. White fat cells are full of fat. This is how the body stores energy. In contrast, brown fat cells contain many mitochondria. ‘These are the powerhouses of the cell,’ explains Alba Sabaté Pérez, postdoctoral research fellow at the Erasmus MC. Brown fat cells actually burn fat, producing heat in the process. This is how we keep our body temperature constant.

Ice bath

People with obesity have less active brown fat. Activating brown fat to burn fat could help them lose weight. A well-known way to activate brown fat is exposure to cold. When cold, brown fat is turned on to keep the body warm. Cold showers and ice baths, then? ‘That would not be a popular treatment,’ says Sabaté Pérez. ‘We will look for other mechanisms to activate brown fat.’

Underlying her quest is the difference between men and women. ‘Women with obesity are generally healthier than men with obesity. Diseases associated with obesity, such as diabetes and cardiovascular disease, are more common in men.’ The cause of these differences is not yet known. But Sabaté Pérez does have her suspicions. ‘Maybe brown fat plays a role in that difference between men and women.’

‘You can hardly reach brown fat’

Women have more active brown fat, is Sabaté Pérez’s expectation. She bases this on earlier studies in humans and on mouse research by her fellow researchers at Internal Medicine. From that, it is clear: female mice have more active brown fat than male mice. The brown fat cells of female mice also look different. Sabaté Pérez wants to prove that this is also true in humans, and most importantly, find out what’s behind it.

Ideally, Sabaté Pérez would like to examine biopsies of brown fat from men and from women. But it’s very difficult to obtain this. Brown fat is well hidden in the body, for example between the vertebras. Sabaté Pérez: ‘To reach brown fat, you need a delicate surgery.’ Cells that you can keep alive for a long time in a culture dish are also not an option. No male and female versions of these cell-lines are available.

Making her own

Sabaté Pérez therefore decided to develop her own male and female brown fat cells. She does this with stem cells. Stem cells can develop into different cell types, including brown fat cells. The cells she is going to use come from blood of healthy male and female donors. These cells are first made into stem cells. They are then called ‘induced pluripotent stem cells’. Then Sabaté Pérez causes them to develop into brown fat cells.

‘We hope to find differences between male and female cells,’ Sabaté Pérez says. ‘And to be able to use those differences to design new strategies to activate brown fat.’ Could this lead to the solution for obesity? ‘Obesity is a complex disease,’ Sabaté Pérez nuances. ‘It is not only dependent on brown fat.’

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