Choline-derived phosphatidylcholine has diverse functions including being necessary for
packaging and exporting triglycerides from the liver. Choline deficiency induces fatty
liver, which occurs very commonly in overweight and obesity, emphasizing the importance
of choline in lipid metabolism. Studies suggest the role of gut microbiota and host
genetics in influencing choline availability, which gut microbes can convert choline to
trimethylamine, and hepatically oxidized by flavin monooxygenase 3 to
trimethylamine-N-oxide (TMAO), a recently emerged marker of disease. We have recently
shown that phosphatidylcholine (the major form of choline in food) leads to higher plasma
concentrations of choline without raising TMAO compared to no choline control, which
metabolic heterogeneity in TMAO response that appears to be a function of individual gut
microbiota composition. However, the effect of phosphatidylcholine on parameters of liver
health and function in the context of obesity has not been examined. This study will
leverage a whole-food approach using eggs, which are enriched in phosphatidylcholine, as
a modulator of metabolic health with a focus on interindividual variation in response.
The study objectives are: 1) determine the effect of additional daily intake of eggs on
metabolic outcomes (liver density and enzymes, circulating lipids and glucose levels,
body mass index and adiposity); 2) assess the effects of additional daily intake of eggs
on levels of choline and downstream metabolites including TMAO; 3) determine the relation
between outcome variables in response to additional daily intake of eggs and metabolic
modifiers including the gut microbiota composition and genetic polymorphism. To achieve
these objectives, Phase I of the larger study will be conducted, which will have multiple
"hits" to form the basis of targetable outcomes. Participants will be asked to keep their
habitual diet during the 4-week baseline period, followed by 4 weeks of additional daily
intake of 3 whole eggs (intervention) then 4 weeks without daily intake of eggs as a
washout. Participants will be free-living and will not be supplied with any other food
except for the eggs during the intervention period with no restrictions of energy intake.
Participants will make clinic visits every 4 weeks for 12 weeks. At their first visit
(week 0), before the intervention (week 4), after the intervention (week 8) and after the
washout (week 12), participants will arrive overnight-fasted and liver imaging will be
performed. Fasting blood will be obtained by a phlebotomist using a standard venipuncture
procedure. Anthropometric measures including waist and hip circumferences and BMI will be
collected. Participants will also be asked to turn in their fecal sample in a
thermos-insulated bag with ice packs. All samples will be de-identified, distributed
among storage vials and stored at -80°C until further analyses.