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Zinc Finger Protein 949 as a Potential Transcriptional Suppressor of Adipocyte Hypertrophy - Resubmission - 1

Award Number: R03DK138218
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Zinc Finger Protein 949 as a Potential Transcriptional Suppressor of Adipocyte Hypertrophy - Resubmission - 1 - Background: The cellular events that cause adipocytes to increase lipid capacity (hypertrophy) characteristic of obesity remain largely unknown. We have discovered that mice with targeted genetic deletion of diaphanous 1in adipose tissue are protected from diet-induced obesity and exhibit reliably elevated levels of the gene encoding the zinc finger protein 949 (Zfp949) in both brown and white adipose tissue. There is only limited published information regarding the physiological role of Zfp949 but what is available has identified Zfp949 as transcriptional suppressor of embryonic development. Preliminary data from our laboratory discovered that genetic manipulations that result in lowering the expression of Zfp949 in adipocytes causes those cells to accumulate significantly more triglycerides than control cells throughout the differentiation process. Thus, this novel model of adipocyte hypertrophy will allow us to identify the precise cellular changes that account for the increased lipid accumulation in Zfp949 knock-down adipocytes. Furthermore, the proposed studies aim to determine whether increasing the expression of Zfp949 represent a therapeutic target for the treatments and/or prevention of obesity. Hypothesis: In line with a common function of proteins in the zinc finger family and based on a published report supporting this role, we hypothesize that Zfp949 functions as suppressor of genes and proteins that promote lipid buildup in adipocytes. Furthermore, we hypothesize that adipocytes genetically altered to overexpressed Zfp949 will be protected from adipocyte hypertrophy and therefore it may represent a potential therapeutic target for the treatment and/or prevention of obesity and other diseases associated with excess lipid buildup. Approach: We will leverage RNA sequencing, proteomic and lipidomic studies to perform an unbiased assessment of the genes, proteins and lipid classes that underlie adipocyte hypertrophy and thereby gain insight into the cellular mechanisms that promote hypertrophy. Similarly, we will also harness those tools to assess whether or not overexpressing Zfp949 represents a potential therapeutic approach to treat obesity. Significance: One of the limitations to being able to study the cellular processes that take place in adipocytes during hypertrophy is that currently it is not technically feasible to isolate hypertrophied adipocytes from subjects in vivo to be able to identify the precise cellular changes that promote lipid accumulation. Here, we provide a new cellular model that will allow for detailed studies on the underlying cellular processes that promote adipocyte hypertrophy in vitro. Furthermore, in light of the lack of effective treatments for obesity, the fast growing prevalence of obesity and the fact that obesity is a risk factor for cardiovascular disease and diabetes, if is of paramount importance to be able to identify novel therapeutic targets for obesity. The clinical significance of the proposed work is that it will test whether overexpression of Zfp949 represents a targetable approach for the treatment and/or prevention of obesity and other lipid-dependent disorders.


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 = -$11,402 )
2025	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/1/2025	NEW	-$117,125
2025	2024	NEW YORK INSTITUTE OF TECHNOLOGY	1855 BROADWAY	NEW YORK	NY	10023	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	4/2/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$105,723
														Subtotal = -$11,402

Issue Date FY: 2024 ( Subtotal = $127,125 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/8/2024	NEW	$127,125
														Subtotal = $127,125

Grand Total All Awards = $115,723

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Zinc Finger Protein 949 as a Potential Transcriptional Suppressor of Adipocyte Hypertrophy - Resubmission - 1

Award Number: R03DK138218

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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