SUMMARYCHILDHOOD OBESITY IS AN EPIDEMIC IN THE UNITED STATES WHERE 32% OF CHILDREN AND ADOLESCENTS AGES 2-19 ARE OVERWEIGHT (BMI&LT;85TH PERCENTILE) AND 16.9% ARE OBESE (BMI&GT;95TH PERCENTILE). TEN PERCENT OF INFANTS AND TODDLERS HAVE HIGH WEIGHT-FOR-RECUMBENT LENGTH MEASUREMENTS PUTTING THEM AT RISK DEVELOPING CHILDHOOD OBESITY. OBESE CHILDREN ARE MORE LIKELY TO EXHIBIT ATTENTION DEFICIT/HYPERACTIVITY DISORDER (ADHD), DEPRESSION, LEARNING DISABILITY AND DEVELOPMENTAL DELAY. IT HAS BEEN PROPOSED THAT A COMMON UNDERLYING DYSFUNCTION, THE OVERSUPPLY OF INFORMATION IN THE FORM OF NUTRITIONAL OR SENSORY CONTENT, MAY INDEPENDENTLY PREDISPOSE CHILDREN TO BOTH OBESITY AND ADHD. A CRITICAL GAP IN THE LITERATURE IS THE IDENTIFICATION OF FOOD-SPECIFIC BIOMARKERS ASSOCIATED WITH OBESITY. OUR PRELIMINARY DATA INDICATE THAT THE CONSUMPTION OF SINGLE-SOURCE, SOY-BASED DIETS IS ASSOCIATED WITH INCREASED SEIZURE SUSCEPTIBILITY AND BODY MASS INDEX (BMI). INCREASED BMI IS A RISK FACTOR FOR THE DEVELOPMENT OF OBESITY, METABOLIC SYNDROME AND TYPE 2 DIABETES MELLITUS (T2DM). WE HYPOTHESIZE THAT HIGH CONSUMPTION OF SOY-BASED INFANT FORMULA, PARTICULARLY IN BABIES THAT ARE GENETICALLY PREDISPOSED TO DEVELOPMENTAL DISABILITIES, IS AN ENVIRONMENTAL EXPOSURE THAT INCREASES THE RISK OF DEVELOPING OBESITY. AS MANY AS 25% OF INFANTS CONSUME SOY-BASED INFANT FORMULA DURING THEIR FIRST YEAR OF LIFE, BUT THERE IS A PAUCITY OF INFORMATION REGARDING POTENTIAL HEALTH EFFECTS. THROUGH THIS R01 APPLICATION IN RESPONSE TO PAR-15-024, "FOOD SPECIFIC MOLECULAR PROFILES AND BIOMARKERS OF NUTRIENT INTAKE, AND DIETARY EXPOSURE," WE EXPECT TO IDENTIFY METABOLIC AND PROTEOMIC BIOMARKERS, IN BOTH CONTROL AND DISEASE MODEL MICE, WHICH ARE ALTERED IN RESPONSE TO THE CONSUMPTION OF SOY PROTEIN. POSITIVE FINDINGS COULD HAVE POWERFUL TRANSLATIONAL IMPLICATIONS IN TERMS OF REDUCING THE INCIDENCE OF CHILDHOOD OBESITY THROUGH DIETARY RESTRICTION OF SOY-BASED INFANT FORMULAS.THIS CONTRIBUTION UTILIZES STATE-OF-THE-ARTMASS SPECTROMETRY TECHNIQUES TO IDENTIFY NOVEL DIETARY BIOMARKERS UNDER RIGOROUS SCIENTIFIC METHODS. THE TANGIBLE BENEFITS OF THIS CONTRIBUTION ARE MANIFOLD. FIRST, THERE IS HIGH POTENTIAL TO IDENTIFY DIETARY BIOMARKERS FOR CLINICALLY MONITORING METABOLIC CHANGES. OFTEN STUDIES OF HUMAN DISORDERS LACK AN IDEAL PROXY TISSUE THAT COULD AID PERSONALIZED MEDICINE FOR DIAGNOSIS AND TREATMENT. IN THIS PROPOSAL, WE HAVE THE OPPORTUNITY TO TEST PLASMA, BRAIN AND PERIPHERAL TISSUE FROM THE SAME MICE IN BOTH WILD TYPE AND A DISEASE MODEL. THIS PROVIDES THE OPPORTUNITY TO IDENTITY NUTRITIONAL BIOMARKERS IN AN ACCESSIBLE PROXY TISSUE AND IN RESPONSE TO DISEASE STATUS. BIOMARKERS FOUND HERE CAN BE DIRECTLY TESTED IN FUTURE CLINICAL STUDIES. MOREOVER, THE PROTEINS IDENTIFIED IN THIS STUDY CAN BE INTERROGATED IN FUTURE STUDIES FOR PSYCHIATRIC- AND OBESITY-RELATED GENETIC VARIANTS IN AT-RISK PATIENTS. THUS, THIS PROPOSAL MAY HELP BRIDGE THE GAP BETWEEN BASIC AND CLINICAL RESEARCH IN THE FIELD OF NUTRITIONAL BIOMARKERS. SECOND, THE FINDINGS WILL INFORM SUBSEQUENT THINKING AND RESEARCH IN THE FIELD OF PEDIATRIC NUTRITION, PARTICULARLY IN REGARD TO INFANTS WITH DEVELOPMENTAL DISABILITIES THAT ARE COMORBID WITH OBESITY SUCH AS PRADER-WILLI SYNDROME, AUTISM SPECTRUM DISORDERS, DOWN SYNDROME, AND FRAGILE X SYNDROME. AND THIRD, POSITIVE FINDINGS WOULD SUPPORT INCREASED DISSEMINATION REGARDING THE BENEFITS OF BREAST-FEEDING, AND IN CASES WHERE FORMULA IS REQUIRED, A DIETARY INTERVENTION (SOY RESTRICTION) TO IMPROVE MEDICAL OUTCOMES. THE AMERICAN ACADEMY OF PEDIATRICS RECOMMENDS INFANTS BE BREASTFED EXCLUSIVELY FOR THE FIRST SEVERAL MONTHS AND THAT BREASTFEEDING CONTINUE THROUGH THE FIRST YEAR OF LIFE. WHILE 83% OF MOTHERS INITIATE BREASTFEEDING, ONLY 50% ARE BREASTFEEDING AT 6 MONTHS AND 24% AT 12 MONTHS. OVER HALF OF NEWBORNS RECEIVE FORMULA IN THE HOSPITAL. APPROXIMATELY 20-25% OF INFANTS RECEIVE SOME SOY-BASED FORMULA DURING THEIR FIRST YEAR, BUT THERE IS NO DATA REGARDING HOW MANY AREEXCLUSIVELY FED SOY-BASED FORMULA. BECAUSE DIETARY RESTRICTION OF SOY, LIKE SUGAR OR WHEAT, IS NOT REGULATED BY THE FDA AND POSES NO HEALTH HAZARDS IN AN OTHERWISE BALANCED DIET, THIS TYPE OF MEDICAL INTERVENTION COULD BE RAPIDLY IMPLEMENTED.