“Battle of the bulge” may be linked to body clock in immune cells

It’s all in the timing, according to Texas A&M researchers who have confirmed disruption of the internal biological clock plays a key role in the development of metabolic diseases, including obesity and diabetes. Their study, published in the Journal of Biological Chemistry, suggests a high-fat diet alters the timing of our body clock, particularly in immune cells that are involved in mediating inflammation in obesity.

Our “body clock” is located in virtually all cells and controls circadian rhythms, 24-hour cycles that tell our bodies when to sleep and regulate many physiological processes, including inflammation and metabolism. When our circadian rhythms are disrupted, sleeping patterns and metabolism become unbalanced, notes study authors David Earnest, PhD, professor at the Texas A&M Health Science Center College of Medicine’s Department of Neuroscience and Experimental Therapeutics and Chaodong Wu, PhD, associate professor in the Department of Nutrition and Food Sciences at the Texas A&M College of Agriculture and Life Sciences. With combined interests in sleep cycles and nutrition, the duo has jointly explored effects of unhealthy eating on circadian rhythms for a number of years.

“Under normal conditions, circadian clocks help maintain the anti-inflammatory function of immune cells and keep metabolism functioning properly,” said Earnest. “With a high-fat diet, the circadian clock is dysregulated, which intensifies inflammation and fat deposition and leads to systemic insulin resistance and glucose intolerance.”

Earnest notes the internal body clock is akin to a watch. When you have a watch with a weak battery, your watch “loses time,” as do you. You will think it’s 3 p.m., when, because the watch is now running slow, it’s actually 9 p.m. Saturated fatty acids have the same effect as weak watch batteries, making our clocks run long.

Using an animal model, the team tested the effects of over-nutrition on body clocks. The test group was fed a high-fat diet and controls were fed a low-fat diet. The study found that a high-fat diet increased the normal functioning body clock from a 24-hour cycle to a 30-33 hour cycle, particularly in immune cells involved in mediating inflammation. This, in turn, results in six to nine hours of time lost each day, causing critical inflammatory and metabolic processes to occur at abnormal times throughout the day.

“As key components of inflammation in obesity, immune cells contain circadian clocks that regulate daily rhythms in inflammatory responses,” Earnest said. “Our experiment was able to demonstrate that a high-fat diet alters the molecular ‘gears’ of the clock along with the inflammatory responses in these immune cells, which can lead to metabolic disorders.”

The team also conducted novel “bone marrow transplantation” experiments to allow circadian clock disruption only in immune cells used to “re-populate” immuno-deficient recipients.

“The mere ‘breakdown’ of circadian clocks in these immune cells increased adipose and liver tissue inflammation, fat deposition and systemic metabolic dysfunction caused by a high-fat diet,” Wu said.

Independent data from the researchers suggests that “bad” saturated fatty acids (common in high-fat diets) perturb circadian clocks at specific times of the day/night when their pro-inflammatory effects are maximal. With these findings, Earnest is working on a complementary study to show that specific polyunsaturated “good” fatty acids or drugs that target inflammatory pathways could prevent the effects of saturated fatty acids, in both dysregulating the clock and increasing pro-inflammatory responses.

Findings could ultimately lead to therapeutic strategies for treating obesity-related metabolic disorders, especially the progression of insulin resistance in type 2 diabetes and other inflammation-related health disorders such as cardiovascular disease, stroke, arthritis and even recovery from injury-induced inflammation, common in sports injuries.

“Keeping our body clock running properly is vital,” Earnest said. “To promote health, we need to eat healthy foods, and more importantly keep a healthy lifestyle, which includes avoiding sleeping late and eating at night. Time your body right and it will work better.”