Circadian influences on lipid metabolism

Many biological processes are coordinated over time, creating rhythms of biological activity around the 24-hour day. In modern society, humans are often in situations where our behavior or environment – electric lights, food at all hours and shift work, for example – fights the biological circadian clock that coordinates these processes, a conflict that is implicated in a range of health problems from cancer to heart disease.

And it’s not just in humans. A new study by researchers at Julius-Maximilians University in Würzburg, Germany, led by Agnes Fekete and Christian Wegener, provides insights into how the circadian clock and the external environment together regulate lipid metabolism in fruit flies.

The work, recently published in the Journal of Lipid Research, draws on Wegener’s and Fekete’s complementary fields: Wegener studies the circadian clock and Fekete lipid metabolomics. At the intersection were unanswered questions that intrigued them both.

“This combination of expertise that we have makes this special,” Wegener said. 

They were curious about lipid levels in hemolymph because this insect blood can serve as a window into metabolism at any given moment. “We were very surprised that there is no publication on the lipid oscillation in the hemolymph,” Wegener said.

They had some doubts that they’d see circadian regulation of lipids this way because so many external influences affect what is in hemolymph at any time.

 “When we started this project, we said, ‘Oh of course it won't be rhythmic — we eat. We don't have any regulation from the body — it's all what we eat,’” Fekete said.

They addressed this by feeding the flies a diet lacking lipids; all lipids in the hemolymph had to come from biological processes.

When the flies ate this lipid-free diet, the researchers were amazed to see a clear rhythmicity of lipid transport, with peaks of lipids surrounding the times the lights were turned on in the morning and off at night (an effect that was hidden when the flies ate a lipid-containing diet), indicating underlying circadian control of lipid transport. 

They then tracked the effects of activity, feeding, light and a circadian clock mutation. Flies kept in darkness cycled only once per day, while flies with a mutation in the circadian clock didn’t cycle, indicating that the biological circadian clock drives rhythmic lipid transport, while light and dark cycling sets the timing. Activity and feeding behavior didn’t drive the lipid peaks, so the peaks appear to prepare the body for predicted times when it needs to build and restore itself.

Next, Fekete and Wegener want to look into the source of lipids, as well as at other external influences, such as offset light and dark cycles to resemble shift work or a light-polluted environment. 

Knowing that organisms regulate lipid transport around the circadian clock has implications for both human biology and the natural world.  Flies, like those in the study, and pollinators such as bees also live in our light-polluted world, and we may inadvertently influence their metabolism.

Wegener summed up the relevance of constant clock disruption: “The clock is really good to optimize things but not required. We can live without the clock. However, if you mask the clock for a long time, then you will end up with problems.”