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REGULATION OF NEONATAL MUSCLE PROTEIN SYNTHESIS

Award Number: R01HD085573
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2016
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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REGULATION OF NEONATAL MUSCLE PROTEIN SYNTHESIS - ABSTRACT Most premature infants experience extrauterine growth restriction for reasons that are unclear and are at in- creased lifelong risk for obesity and type 2 diabetes. Our long-term goal is to identify mechanisms that diminish lean growth and alter metabolic responses to nutrition in preterm infants; these findings will inform the develop- ment of new nutritional strategies to improve outcomes. The objective of this application is to determine if per- sistence of the anabolic resistance to feeding following premature birth impairs lean growth and if specific amino acid supplementation ameliorates lean mass accretion. The central hypothesis is that prematurity limits lean growth by blunting amino acid- and insulin-induced stimulation of protein synthesis and myonuclear accretion in skeletal muscle but can be improved by amino acid supplementation targeted to promote mechanistic target of rapamycin complex 1 (mTORC1)-dependent cellular processes. The hypothesis is based on data from the ap- plicants’ laboratories and supported by the literature. The rationale is that understanding the fundamental mech- anisms by which prematurity alters the anabolic response to nutrition is essential to inform and modify feeding practices for preterm infants to sustain intrauterine growth rates of lean mass after they are born. The hypothesis will be tested by pursuing two specific aims: 1) Determine if the acute protein anabolic resistance to feeding in the preterm is sustained long-term and results in reduced muscle and lean mass accretion; and 2) Determine if supplementation with leucine and/or the arginine precursor, citrulline enhances lean growth by upregulating mTORC1-dependent muscle protein synthesis and myonuclear accretion. When pigs born preterm and term reach ages equivalent to human late-infancy or late-childhood, we will determine body composition, growth rate, energy expenditure, hormone, substrate and metabolite profiles, and skeletal muscle protein synthesis and deg- radation rates, blood flow, amino acid, insulin and eNOS signaling, metabolomic and transcriptomic profiles, and satellite cell abundance and proliferation in response to feeding, pancreatic-substrate clamps, and supplemen- tation with leucine and/or citrulline. The methods are established in the applicants’ laboratories. The approach is innovative because it will use comprehensive approaches that will examine concurrently in vivo responses to preterm birth of the principal processes that regulate muscle growth, i.e., protein synthesis, protein degradation, and myonuclear accretion, and how these processes respond to dietary interventions targeted to promote anab- olism. The proposed studies are unique because they comprehensively examine in a relevant preterm model the mechanisms that underlie the anabolic resistance of the premature which limits lean growth and examine the effectiveness of targeted amino acid supplementation on processes that regulate skeletal muscle growth. The proposed research is significant because it will advance our understanding of how prematurity impacts the anabolic response of skeletal muscle to nutrition. The results will provide novel information to optimize the nutri- tional management of preterm infants to improve their long-term metabolic health and growth.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $603,946 )
2025	2025	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Child Health and Human Development Extramural Research	003	25	8/19/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$603,946
2025	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	002	24	8/19/2025	NON-COMPETING CONTINUATION	$0
2025	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	23	1/29/2025	COMPETING CONTINUATION	$5,640
2025	2020	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	22	1/29/2025	NON-COMPETING CONTINUATION	-$5,640
														Subtotal = $603,946

Issue Date FY: 2024 ( Subtotal = $605,251 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	24	5/1/2024	NON-COMPETING CONTINUATION	$605,251
														Subtotal = $605,251

Issue Date FY: 2023 ( Subtotal = $617,549 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	23	8/31/2023	COMPETING CONTINUATION	$617,549
														Subtotal = $617,549

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	22	1/31/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $422,871 )
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	22	4/23/2020	NON-COMPETING CONTINUATION	$422,871
														Subtotal = $422,871

Issue Date FY: 2019 ( Subtotal = $452,425 )
2019	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	21	5/1/2019	NON-COMPETING CONTINUATION	$452,425
														Subtotal = $452,425

Issue Date FY: 2018 ( Subtotal = $481,979 )
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	20	4/19/2018	NON-COMPETING CONTINUATION	$481,979
														Subtotal = $481,979

Issue Date FY: 2017 ( Subtotal = $452,890 )
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	19	6/16/2017	NON-COMPETING CONTINUATION	$45,289
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	19	3/28/2017	NON-COMPETING CONTINUATION	$407,601
														Subtotal = $452,890

Issue Date FY: 2016 ( Subtotal = $420,122 )
2016	2016	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	18	4/15/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$420,122
														Subtotal = $420,122

Grand Total All Awards = $4,057,033

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REGULATION OF NEONATAL MUSCLE PROTEIN SYNTHESIS

Award Number: R01HD085573

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/15/2016

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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