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Time of Eating Plays Critical Role in Weight Gain

by Kathy Jones on November 12, 2012 at 6:38 PM
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 Time of Eating Plays Critical Role in Weight Gain

Pennsylvania researchers looking into why night shift workers tend to be more obese compared to others have found that the time of eating, and not just the type and amount of food, plays an important role in weight gain

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, found 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.

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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 favour energy storage. Our mice became obese without consuming more calories," said Paschos.
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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 behavioural 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 behaviour of the percussionist can, itself, influence the conductor," explained 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 favour food consumption at the time of inappropriate intake - daytime in mice, nighttime in humans.

The Penn team found that only a handful of genes were altered when the clock was broken in fat cells and these governed how unsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were released into the blood stream.

Interestingly, these are the same fatty acids that are typically associated with fish oils. Sure enough, levels of EPA and DHA were low in both plasma and in the hypothalamus at the time of inappropriate feeding.

"To our amazement, we were able to rescue the entire phenotype - inappropriate fatty acid oscillation and gene expression in the hypothalamus, feeding pattern and obesity - by supplementing EPA and DHA to the knock-out animals," noted Paschos.

The findings point to a role for the fat cell clock molecules in organizing energy regulation and the timing of eating by communicating with the hypothalamus, which ultimately affects stored energy and body weight.

Taken together, these studies emphasize the importance of the molecular clock as an orchestrator of metabolism and reflect a central role for fat cells in the integration of food intake and energy expenditure.

"Our findings show that short-term changes have an immediate effect on the rhythms of eating. Over time, these changes lead to an increase in body weight. The conductor is indeed influenced by the percussionist," said FitzGerald.

The findings were reported this week in Nature Medicine.

Source: ANI
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