PHILADELPHIA — Fat cells store excess energy and signal these levels to the brain.  In a new study this week in Nature Medicine, Georgios Paschos PhD, a research associate in the lab of Garret FitzGerald, MD, FRS director of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, shows that deletion of the clock gene Arntl, also known as Bmal1, in fat cells, causes mice to become obese, with a shift in the timing of when this nocturnal species normally eats. These findings shed light on the complex causes of obesity in humans.

The Penn studies are surprising in two respects. “The first is that a relatively modest shift in food consumption into what is normally the rest period for mice can favor energy storage,” says Paschos. “Our mice became obese without consuming more calories.” Indeed, the Penn researchers could also cause obesity in normal mice by replicating the altered pattern of food consumption observed in mice with a broken clock in their fat cells.

This behavioral change in the mice is somewhat akin to night-eating syndrome in humans, also associated with obesity and originally described by Penn’s Albert Stunkard in 1955.

The second surprising observation relates to the molecular clock itself. Traditionally, clocks in peripheral tissues are thought to follow the lead of the “master clock” in the SCN of the brain, a bit like members of an orchestra following a conductor. “While we have long known that peripheral clocks have some capacity for autonomy – the percussionist can bang the drum without instructions from the conductor – here we see that the orchestrated behavior of the percussionist can, itself, influence the conductor,” explains FitzGerald.

Daily intake of food is driven by oscillating expression of genes that drive and suppress appetite in the hypothalamus. When the clock was broken in fat cells, the Penn investigators found that this hypothalamic rhythm was disrupted to favor food consumption at the time of inappropriate intake – daytime in mice, nighttime in humans.

When a species’ typical daily rhythm is thrown off, changes in metabolism also happen. For example, in people, night shift workers have an increased prevalence of obesity and metabolic syndrome, and patients with sleep disorders have a higher risk for developing obesity. Also, less sleep means more weight gain in healthy men and women.

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