Keio Research Highlights

Can't begin the day without a coffee? A morning brew might have broader benefits than just an energizing jolt, new research shows. Previous health surveys have hinted that regular coffee drinkers have a significantly reduced chance of developing obesity and associated diseases such as type-2 diabetes and heart disease. Researchers at Keio University have taken a closer look at these claims, and discovered a molecular mechanism by which coffee inhibits fat cell formation¹.

"Our results provided evidence that drinking coffee has advantages for reducing obesity and its associated diseases," says Megumi Funakoshi-Tago from the Keio University Faculty of Pharmacy, who led the work.

The team's first step was a control experiment in mice. In a study involving 36 animals, just as earlier surveys had predicted, mice on a high-fat diet gained significantly less weight when given a diluted drip-filter coffee extract, the team discovered.

These lean, coffee-fed mice had accumulated less of a fat form called adipose tissue ― the very tissue associated with obesity. "It is well understood that obesity is caused by abnormal 'adipogenesis'," the process by which immature fat cells become fully functional, fat-laden cells called adipocytes, Funakoshi-Tago says. The team homed in on coffee's effects on adipocyte formation, and confirmed that it inhibits the formation of mature adipocyte fat cells.

Drilling down into the cellular signaling pathway known to trigger adipogenesis, the researchers traced coffee's effect to a molecule called insulin receptor substrate 1 (IRS1). In the presence of coffee, a key phosphorus tag on IRS1 is removed, consigning the molecule to the cellular recycling bin and switching off adipocyte formation.

But to realize the full effects of drinking coffee on obesity would demand a serious coffee habit, says Funakoshi-Tago. Weight gain was restricted in mice given the equivalent of 6 to 7 cups of coffee per day. "To prevent obesity, we would have to drink more than 9 cups a day," she adds.

A more efficient route, would be to identify the coffee molecule responsible for the beneficial effect, which could be a lengthy task. "Coffee extract contains a large number of chemical components," Funakoshi-Tago says. "We tested the effects of caffeine, chlorogenic acid, and caffeic acid, which are known to be abundant in coffee extract, however, they had no effect on adipogenesis." The team is now grinding through coffee's other component molecules, looking for the elusive active compound.

1. Maki, C. et al. Coffee extract inhibits adipogenesis in 3T3-L1 preadipocyes by interrupting insulin signaling through the downregulation of IRS1. PLOS ONE 12, e0173264 (2017). | article