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Maternal obesity, AMPK and Developmental Programming

Award Number: R01HD067449
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: 09/27/2010
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Maternal obesity, AMPK and Developmental Programming - Maternal obesity, AMPK and Developmental Programming Over 30% of pregnant American women are obese and an additional 30% are over-weight, conditions which negatively affect fetal development with long-term consequences for offspring health, including pre-disposition to obesity and type 2 diabetes (T2D). The underlying mechanisms remain poorly defined. Skeletal muscle (SM) accounts for >30% body weight and is a key tissue for the oxidation of fatty acids and glucose, as is brown adipose tissue (BAT). Under the support of our previous award, we demonstrated that maternal obesity (MO) elicits early onset of fibrotic and fatty infiltration (FFI) in offspring SM and BAT, which impairs their functions and programs metabolic disorders in offspring. We found that AMP-activated protein kinase (AMPK), a known target for metformin, is robustly inhibited due to MO, correlates with FFI and worsened offspring SM/BAT functions. In the early embryo, both myogenic and fibrogenic cells are derived from progenitor cells (PCs) in the dermomyotome. While the embryonic myogenic cells are the sources of both myogenic and brown adipogenic cells, embryonic fibrogenic cells are sources of fibrogenic and white adipogenic cells in offspring SM/BAT. Because of this, our previous studies point to embryonic origins for developmental abnormalities of offspring SM/BAT due to MO, but this is yet to be examined. Using single cell RNA sequencing (scRNA-seq), we found that embryonic myogenesis is attenuated in E9.5 MO embryos. We hypothesize that MO suppresses AMPK, which inhibits myogenic commitment and drives uncommitted PCs to fibrogenesis during embryonic development, programming FFI in offspring SM/BAT. Accordingly, we have three specific aims: 1) Study AMPK inhibition due to MO in impairing embryonic myogenic commitment; 2) Evaluate AMPK in linking MO to enhanced embryonic fibrogenesis; and 3) Analyze AMPK as a target for improving embryonic SM/BAT development of MO and the resulting offspring SM/BAT functions. We will use single cell “omics” for analyzing embryonic tissues, and embryoid body culture for mechanistic exploration. Knowledge obtained will identify molecular targets for therapeutics to improve embryonic SM/BAT development and subsequent metabolic health of MO offspring, helping the increasing populations of obese mothers to deliver healthy children.


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 = $377,108 )
2025	2025	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	14	7/18/2025	NON-COMPETING CONTINUATION	$377,108
														Subtotal = $377,108

Issue Date FY: 2024 ( Subtotal = $373,338 )
2024	2024	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	13	7/22/2024	NON-COMPETING CONTINUATION	$373,338
														Subtotal = $373,338

Issue Date FY: 2023 ( Subtotal = $377,108 )
2023	2023	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	002	12	7/13/2023	NON-COMPETING CONTINUATION	$377,108
2023	2022	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	001	11	12/30/2022	COMPETING CONTINUATION	$199,497
2023	2021	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	10	12/30/2022	NON-COMPETING CONTINUATION	-$199,497
														Subtotal = $377,108

Issue Date FY: 2022 ( Subtotal = $377,108 )
2022	2022	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	001	11	7/27/2022	COMPETING CONTINUATION	$377,108
2022	2021	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	10	7/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $377,108

Issue Date FY: 2021 ( Subtotal = $311,125 )
2021	2021	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	10	7/13/2021	NON-COMPETING CONTINUATION	$311,125
														Subtotal = $311,125

Issue Date FY: 2020 ( Subtotal = $317,475 )
2020	2020	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	9	7/20/2020	NON-COMPETING CONTINUATION	$317,475
														Subtotal = $317,475

Issue Date FY: 2019 ( Subtotal = $311,606 )
2019	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	8	7/19/2019	NON-COMPETING CONTINUATION	$311,606
														Subtotal = $311,606

Issue Date FY: 2018 ( Subtotal = $311,991 )
2018	2018	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	7	7/26/2018	NON-COMPETING CONTINUATION	$311,991
														Subtotal = $311,991

Issue Date FY: 2017 ( Subtotal = $312,349 )
2017	2017	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	001	6	7/31/2017	COMPETING CONTINUATION	$312,349
2017	2014	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	5	12/6/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $312,349

Issue Date FY: 2014 ( Subtotal = $231,571 )
2014	2014	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	5	7/24/2014	NON-COMPETING CONTINUATION	$231,571
														Subtotal = $231,571

Issue Date FY: 2013 ( Subtotal = $226,093 )
2013	2013	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	4	7/23/2013	NON-COMPETING CONTINUATION	$226,093
														Subtotal = $226,093

Issue Date FY: 2012 ( Subtotal = $238,243 )
2012	2012	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	3	7/13/2012	NON-COMPETING CONTINUATION	$238,243
														Subtotal = $238,243

Issue Date FY: 2011 ( Subtotal = $238,243 )
2011	2011	WASHINGTON STATE UNIVERSITY	FRENCH ADMIN BLDG, ROOM 240K	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	2	7/25/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$238,243
														Subtotal = $238,243

Issue Date FY: 2010 ( Subtotal = $234,890 )
2010	2010	UNIVERSITY OF WYOMING	P.O. BOX 3355	LARAMIE	WY	82071	ALBANY	USA	Child Health and Human Development Extramural Research	000	1	9/28/2010	NEW	$234,890
														Subtotal = $234,890

Grand Total All Awards = $4,238,248

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Maternal obesity, AMPK and Developmental Programming

Award Number: R01HD067449

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: 09/27/2010

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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