Inflammation, circadian rhythm, and beyond
PHILADELPHIA -- It's not just the actual food eaten, but also the timing and potential effects of inflammation that matter in diet‐induced cardiac dysfunction, translational research is showing.
For example, the NLRP3 inflammasome, a multi-part protein complex, can initiate cell death and inflammation when primed or triggered by dietary components such as saturated fatty acids and cholesterol, said Stefano Toldo, PhD, of Virginia Commonwealth University in Richmond.
Inhibition of NLRP3 and other inflammasomes thus represents a target to reduce adverse remodeling and cardiac dysfunction, he told the audience here at a food-focused session at the Heart Failure Society of America's annual meeting.
Another key piece of the inflammation puzzle is the role of microbes, which are thought to act as inflammatory modulators in heart failure progression -- and food is known to have an impact on metabolite levels and microbiome diversity, according to W. H. Wilson Tang, MD, of the Cleveland Clinic.
"Gut bacteria and their ability to modify our ingested food can have diverse impact on development and progression of cardio-renal diseases," Tang said at the session. "No matter what disease you have, there's a reduction in diversity of bacterial species."
For instance, researchers are trying to directly target the trimethylamine N-oxide (TMAO) pathway in which gut bacteria create an atherogenic byproduct from food components rich in choline, lecithin, and carnitine. Notably, human studies suggest that caloric restriction, intermittent fasting, decreased red meat consumption, vitamin B and D supplementation, and the Mediterranean diet lead to lower TMAO levels, Tang said.
Ultimately, the TMAO research is a prototype for learning how host and microbe interact, he said. Whether this actually prevents disease is the real question -- followed by whether people at risk can be identified for an intervention.
What is "good food" and "bad food" may be different for different people, Tang acknowledged.
Another challenge in these diet studies is that the multitude of bacteria "flying around" inside and outside of us makes it hard to reproduce these data.
Furthermore, food is a "really complex material," the presenter added. "When we do a microbiome study, pills and food react very differently."
Around the globe, dietary micronutrient insufficiencies are common and no single food group will solve this problem, added Terry Lennie, RN, PhD, of the University of Kentucky, Lexington. Such deficiencies -- most commonly calcium, magnesium, folate, zinc, and vitamins D, E, C, and K -- were linked to subsequent heart failure events in a study by Lennie's team.
Meal times, too, apparently play a role in how food intake affects heart function.
Circadian rhythm (the idea that present in every cell is a molecular clock) is driven by transcriptional mechanisms such that different times of day drive different processes, such as oxidation, nutrient storage, and cellular turnover, said Martin Young, PhD, MS, of the University of Alabama at Birmingham.
Mouse experiments show that disrupting the clock through diet -- routine high-fat meals eaten during the animal's "sleep phase," akin to "a pizza before going to bed," Young said -- hurts cardiac function after 16 weeks, whereas such fatty meals during the "awake phase" have no such detriment.
Other groups are trying to translate this finding to humans, according to Young. His group is now challenging the mice with protein at different times of day with the idea that excess amino acids introduced during a time when the heart is remodeling might cause hypertrophic growth, Young told the audience.
Lennie and Young disclosed no conflicts.
Tang declared consulting for Sequana Medical and MyoKardia.
Toldo reported research support from Serpin Pharma, Olatec Therapeutics, and Kiniksa.
Read the original article on Medpage Today: Translational Research: Diet Affects the Heart in Multiple Ways