Eat more, move less and lose weight — sounds too good to be true. Yet this is exactly what Julia Fischer and her colleagues observed in mice lacking one specific gene (J. Fischer et al. Nature advance online publication doi:10.1038/nature07848; 2009).
Obesity is a complex disorder because, as well as environmental factors, many genes seem to be involved. One such gene is FTO, as several studies have indicated that different versions of FTO are strongly correlated with body mass index: individuals carrying the high-risk version weigh roughly 3 kilograms more than those with the low-risk version.
Fischer et al. studied mice lacking Fto (Fto−/− mice) and compared them with normal mice and with those carrying only one copy of the gene (Fto+/− mice). The absence of Fto did not affect embryonic development, but by six weeks after birth, Fto−/− mice weighed on average 30–40% less than normal or Fto+/− mice. This reduction in weight was associated with a marked loss of white fat tissue, with near-complete loss by 15 months.
The lower weight of the mutant mice doesn't seem to be due to reduced calorific intake. In fact, these mice ate more in proportion to their body weight than normal mice. Moreover, on a high-fat diet, both groups of mutant mice gained much less weight than normal animals. Instead, Fto−/− mice used more energy, while not moving much. The authors suggest that this increased energy expenditure might be due to higher activity of the sympathetic nervous system — that is, to enhanced circulating levels of adrenaline and noradrenaline.
Fischer and colleagues' data indicate that variations in the human FTO gene might affect its levels of expression, either putting individuals at risk of obesity or protecting them from it. It remains to be seen how FTO might regulate the activity of the sympathetic nervous system.
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