Fat flies show how bodies access energy stores
German researchers have shed new light on how fruit flies control fat storage and mobilisation. Maintaining the correct level of body fat is vital for survival; storing too little fat puts you at risk of starvation in times of famine, while too much fat can lead to an increased risk of diseases such as cardiovascular disease, type II diabetes and cancer. Little is known about the processes regulating the storage and release of fat reserves. In a previous study, Ronald Kühnlein and his colleagues at the Max Planck Institute for Biophysical Chemistry worked out how fruit flies (Drosophila) lay down their fat reserves. Like mammals, they store fat in the form of droplets in the cells of special storage tissue. 'The chemical composition of this stored fat is identical,' said Professor Kühnlein. 'In both cases it is a triglyceride.' However, it is not enough to be able to store fat - you also need to be able to access and use the fat when needed, and it is this 'mobilisation' process which is the subject of the latest study. 'When fat needs to be metabolised, you need fat-splitting enzymes: the brummer lipase in insects and in mammals the so called ATGL [adipose triglyceride lipase],' explained Professor Kühnlein. The researchers studied fruit flies who were unable to produce the brummer lipase enzyme correctly, as well as flies in which the receptor for the adipokinetic hormone (AKH) was defective. The AKH receptor activates a signalling pathway which leads to the mobilisation of fat reserves. They also studied flies in which both the brummer lipase enzyme and the AKH receptor were defective. All the flies were given as much food as they liked and then starved to see if and how they would mobilise their fat stores. The flies in which one of these genes was defective were significantly fatter than normal flies. However, although their ability to mobilise their fat reserves was limited, they were able to survive food deprivation for a long time. Flies in which both genes were defective became four times as fat as normal flies and accumulated excessive fat droplets in their fat body cells. However, when food was withdrawn, these double mutant flies quickly died of starvation. 'They had no access at all to their fat reserves,' explains Professor Kühnlein. 'This means that in Drosophila there are only two mechanisms for fat mobilisation. For if both mechanisms are switched off and the flies, in spite of all their body fat, soon die without food, there can be no third way to access the fat stores.' These flies were however able to access and make use of their carbohydrate reserves, showing that the brummer and AKH mutants only affect access to fat reserves, and not other energy stores in the body. The next step for researchers is to understand how the brummer and AKH pathways interact with each other, and also to identify other genes involved in fat storage and mobilisation. There is also the question of what mechanisms are involved in these processes in humans; we also have receptors which are similar to the flies' AKH receptor, and which are known to play a role in fat metabolism.
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