New research indicates that cancerous lung tumors can alter metabolism and impact the way circadian rhythms control liver function.

Their research, published online today in Cell, is the first showing that lung adenocarcinoma can affect the body clock’s sway over lipid metabolism and sensitivity to insulin and glucose.

Paolo Sassone-Corsi and Selma Masri of UCI’s Center for Epigenetics & Metabolism and colleagues found in rodent studies that lung adenocarcinoma sends signals to the liver through an inflammatory response, which rewires the circadian mechanisms that manage metabolic pathways. As a result of this inflammation, the insulin signaling pathway is inhibited in the liver, leading to decreased glucose tolerance and reorganization of lipid metabolism.

“It seems that lung tumors take control of circadian metabolic function in the liver, potentially to support the heightened metabolic demands of cancer cells,” said Masri, a research scientist in the Sassone-Corsi lab. “We believe that this distal rewiring of metabolic tissues does not occur only in the liver, suggesting a systemic shake-up of metabolism.”

Circadian rhythms of 24 hours govern fundamental physiological processes in virtually all organisms. The circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental fluctuations and adapt to suit the time of day. Changes to these rhythms can profoundly influence human health. Up to 15 percent of people’s genes are regulated by the day-night pattern of circadian rhythms; nearly 50 percent of those involved with metabolic pathways in the liver are affected by these rhythms.

Photo Credit: Steve Zylius/ UCI

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