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Tick-tock of stem cell circadian clock controls when fat cells mature, Stanford research shows

Stem cells that give rise to fat have their own circadian clock, and it ticks a bit differently than the clocks in other cells, according to Stanford research that appears in Cell Reports.

Not only does the clock mechanism use different proteins as its "gears" than most other cells, this clock also plays a role in cell development that surprised the research team, led by pediatric endocrinologist Brian Feldman, MD, PhD. The clock controls when these stem cells, known as adipocyte precursor cells, make the decision to mature into adipocytes, ready to store fat.

Several different hormones can cause adipocyte precursor cells to turn into mature adipocytes in a lab dish, but surges of the individual hormones don't always make the cells mature inside the body. Instead, the clock machinery integrates all the hormonal signals and makes the final decision for the cells, Feldman's team discovered. The finding is especially interesting in light of the long-recognized but poorly understood links between disturbed sleep patterns and metabolic disease. Our press release explains:

Extensive research has shown that late-shift workers, who are awake at night and asleep during the day, are at increased risk for diabetes and obesity. But scientists have not known why.

'This work is connecting the dots of how altered biological rhythms can lead to metabolic derangement,' Feldman said. In those who sleep at night, the adipocyte precursor cells’ circadian clock guards against maturing too many fat cells. 'But what happens in shift workers is that this ends up working against you,' he said. 'If the rhythm of making mature adipocytes is thrown off and you’re not making adipocytes when you should, that may place you at greater risk for diabetes in the future.'

This research also has an interesting tie to the 2017 Nobel Prize in Physiology or Medicine, which recognizes three scientists who discovered the basic molecular mechanics of circadian clocks. Feldman first became fascinated with circadian biology while working as an undergraduate student in the lab of one of the new Nobel laureates, Michael Rosbash, PhD, of Brandeis University.

"His winning the prize made me reflect on how formative that early experience was, and how I built my medical expertise on that foundation," Feldman told me in a recent e-mail. "All this made me feel a bit philosophical about how every stage of training is impactful -- even playing with fruit flies as an undergrad!"

Previously: Immune cells release "red flag" to activate muscle stem cells in response to damage, New hormone helps explain how high-fat diets make us fatter and Stanford technology enabled circadian clock research that won a Nobel Prize
Photo by fintbo

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