© 2018 by Clara E Cho. Design by Wix.com

The primary goals of our research program include: 1) To determine the fundamental role of methyl nutrients in health outcomes; 2) To determine molecular mechanisms underlying the development of obesity, metabolic syndrome and chronic diseases; and 3) To contribute to evidence-based strategies that will improve the health of the population.

 

Previous research contributions extend to the following:

 

1. Role of maternal intake of methyl vitamins in development of energy regulatory pathways

A high intake of vitamins involved in one-carbon metabolism (folate, vitamins B12 and B6) during pregnancy contributes to the obesogenic phenotype and epigenetic alterations in the hypothalamic feeding pathways in the offspring (Mol Nutr Food Res 2015; 59:476-89; Appl Physiol Nutr Metab 2014;39:844). This work has implications in human health because methyl vitamins are promoted for consumption during pregnancy and they impact development through epigenetic modification of gene expression.

 

2. Plasticity of hypothalamic development of food intake regulatory pathways

The hypothalamic feeding pathways are modified by vitamin composition of the maternal and post-weaning diets (Int J Obes 2013;37:1177-82; Epigenetics 2013;8:710-9). Increasing the vitamin content of the pup diets (i.e., matching the vitamin content between the maternal and pup diets) prevented the obesogenic phenotype associated with high vitamin diet during pregnancy. Not only vitamins exposed in utero determine the risk of chronic diseases in the offspring, but also those in the pup diet can modulate the effect established in early life. The concept of dynamic plasticity of food intake regulatory pathways modified by the post-weaning diets also provides a potential preventive strategy against the onset of chronic diseases.

 

3. Impact of diet and gut microbiome on trimethylamine-N-oxide production and metabolic fate in humans

Trimethylamine-N-oxide (TMAO) is a small organic dietary compound found naturally in our diets (e.g., fish) or can be made from other nutrients such as choline and carnitine (found in eggs and beef). TMAO has recently emerged as a predictive risk factor for heart disease in cardiac patients. However, a higher gut microbial enrichment of Firmicutes relative to Bacteroidetes among men exhibiting greater response to dietary TMAO precursor intake indicates that circulating TMAO may be a marker of the individual gut microbiota composition, rather than a causative agent of disease (Mol Nutr Food Res 2017;61). Moreover, fish consumption which is known for its cardio-protective attributes yielded substantially greater circulating and urinary TMAO concentrations than eggs or beef, indicating that preformed TMAO in fish has the greatest impact on circulating TMAO concentrations. Unlike choline and carnitine, dietary TMAO at physiologically relevant intake levels can by-pass gut microbiome and hepatic processing with near-complete absorption, mostly eliminated unchanged in urine within 24-h and taken up by extrahepatic tissue (J Nutr Biochem 2017;45:77-82). We also highlight that preemptive dietary strategies to restrict TMAO generating nutrients as a means to improve human health warrant careful consideration and may not be justified at this time (Trends Endocrinol Metab 2017;28:121-30).

 

4. Mode of delivery and development of the immune system in the offspring

Children born by elective cesarean section (CS) face a greater risk of developing immune diseases such as asthma, allergies, type 1 diabetes, and celiac disease (Am J Obstet Gynecol 2013;208:249-54; Am J Obstet Gynecol 2013;209:496-7). The potential mechanisms by which CS can impact the development of the immune system may be through alteration of bacterial colonization, adverse birth stress response and epigenetic modification of gene expression in the immune system. With the recent increase in the rate of elective CS, an impetus for the prevention of elective CS without a clear medical indication is required, as such practice may be associated with adverse health of the offspring. This work reaches out to a broad community of health professionals and childbearing women, encouraging discussion that both short- and long-term consequences for the offspring should carry a greater weight than what is considered today.

 

5. Functional food strategies to control blood glucose and food intake in humans

Functional food products and ingredients provide a non-medicinal approach to manage and reduce the risk of metabolic syndrome including type 2 diabetes and obesity. Whey protein administered prior to a meal effectively reduces post-meal blood glucose levels and food intake in humans (patent application in collaboration with Kraft Foods Global Brands LLC, US 2009/#12550091; Am J Clin Nutr 2010;91:966-75). In addition, starch digestibility predicts satiety and glycemic response in humans (Am J Clin Nutr 2010;91:932-9). Because individuals at potential risk for diabetes have elevated blood glucose levels beyond normal levels and remain elevated for a longer period of time following a meal compared to healthy individuals, protein and/or starch pre-meal ingestion may be an effective means to better control blood glucose homeostasis.