The basics of energy balance are not exactly rocket science. If you regularly consume significantly more energy than you burn, then you will gain weight. That being said, obesity is an extremely complex disease, and if solutions were as simple as just eating less, then it seems unlikely that the current worldwide crisis that we are facing would exist. Behavior, diseases, genetics and even our gut microbes can all contribute to obesity, yet it still seems that we don’t know enough about it.
But a new study is offering a boost to our understanding of the processes potentially underlying disease development, with the discovery of a putative “obesity gene.” This gene seems to be involved in a complex network that coordinates the generation of fat cells in the body, helping to regulate the induction of so-called “master” factors that drive fat production. Importantly, when scientists switched it off, mice experienced a significant drop in abdominal fat, despite continuing the same diet.
Interestingly, this particular gene, which codes for a protein called 14-3-3zeta, was not one of those identified in a significant study published earlier this year that found almost 90 stretches of DNA that play roles in obesity development, such as fat distribution. This signaling molecule belongs to a conserved family of so-called adaptor proteins that are known to interact with and facilitate the transport of other molecules, called transcription factors, which help to control gene activity.
During the process of adipogenesis, in which precursor cells become fat cells (adipocytes), several of these transcription factors are needed in the nucleus to switch on master genes that drive this process of cell division and differentiation. Although it was unclear as to whether certain 14-3-3 proteins help the transport of these specific “adipogenic” factors in fat cells, they have previously been found in the fat tissue of obese people, suggesting that they may play key roles in adipogenesis.
To find out if this could be the case, scientists from the University of British Columbia started off by silencing the 14-3-3zeta gene in mice. Before birth, the embryos of these engineered mice were smaller than controls and although they caught up in terms of length by adulthood, they remained significantly lighter. Despite being fed the same diet, the genetically altered mice were much leaner than the controls, with substantially reduced fat mass.
Taking this one step further, the scientists created mice in which 14-3-3zeta was overproduced, which grew up to be noticeably larger than the controls. And when fed a high-fat diet, these animals experienced significantly greater weight gain and fat mass than controls. These findings have been published in Nature Communications.
While interesting, the study does not point to a specific genetic “cause” of obesity; many genes seem to be involved in the development of fat cells, and the research was only conducted in mice. Furthermore, while it has been suggested that blocking 14-3-3zeta could represent a possible treatment avenue for overweight people to prevent fat accumulation, other scientists are not so convinced.
“I would be very dubious of the benefits of such treatment,” Bariatric Physician Nicholas Finer, who was not involved in the research, told IFLScience. “Even if this were a ‘sensible’ approach, the time lag from this sort of science to clinical development is likely to be at least 10–15 years.”