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Defining choline metabolism in metabolic health

Award Number: K01DK144653
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/15/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2030

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Defining choline metabolism in metabolic health - Project Summary The impairment in choline catabolism to its methyl-donor, betaine, is strongly related to the development of metabolic-associated liver disfunction (MASLD). In order for choline to be metabolized, it must be transported into the mitochondrial matrix. However, limitations in the understanding subcellular localization of choline have limited the understanding of choline metabolism in the development of MASLD. My work has identified SLC25A48 as a mitochondrial choline carrier (MChoC, SLC25A48) which regulates choline subcellular localization and metabolism. Elucidating the regulation choline metabolism under obese conditions may reveal novel mechanisms of treating MASLD. This proposal tests the hypothesis that diet induced obesity disrupts choline contribution to the methionine cycle which regulates metabolic health. A first set of studies focuses on the regulation of choline flux in the liver. I will map the fate of choline in the livers of control and MChoC liver- specific knockout (MChoC-LKO) mice through in vivo flux analysis with stable-labeled choline coupled with LC/MS. I will also determine whether overexpression of MChoC in livers of obese mice is sufficient to rescue fatty liver disease. A second set of studies will focus on choline dependent changes in epigenetics. This set of studies will expand my technical training with support from co-mentor Dr. Evan Rosen. To address the epigenetic modifications dependent on choline metabolism we will assess chromatin architecture regulated through histone methylation and translational control through polysome profiling in MChoC-LKO mice. A third set of studies will test the regulation of obesity on the choline metabolic pathway through proximal-labeling and in vivo complex assessment. Completion of these studies will expand the scope of my work, provide foundational datasets, and establish models that will be essential toward achieving my career goal of leading and developing scientists as an independent investigator.


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 = $159,775 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/12/2025	NEW	$159,775
														Subtotal = $159,775

Grand Total All Awards = $159,775

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Defining choline metabolism in metabolic health

Award Number: K01DK144653

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/15/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2030

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