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Role of GPER in Obesity and Lipid Metabolism.

Award Number: F31DK136330
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Role of GPER in Obesity and Lipid Metabolism. - PROJECT SUMMARY/ABSTRACT Obesity poses as a serious and worsening public health issue in the United States and is the second most common cause of preventable death behind smoking. Obesity is associated with the risk of developing additional comorbidities, such as hypertension, atherosclerosis, and diabetes. Estrogens (primarily 17β-estradiol, referred to as E2) can ameliorate weight gain and multiple aspects of metabolic dysfunction. The effects of estrogens are mediated through multiple estrogen receptors (ERs), including the classical nuclear ERs (ERα and ERβ), which traditionally regulate gene expression, and the 7- transmembrane G protein-coupled estrogen receptor (GPER), which predominantly mediates rapid “non- genomic” signaling. Our preliminary results suggest a potential intervention employing a highly selective GPER agonist, with promising outcomes against multiple negative effects of obesity. With the opportunity to employ the GPER-selective agonist G-1 as a novel therapeutic for obesity, understanding the direct effects of GPER in adipocytes is critical. The long-term goal is to determine whether selective activators of GPER, such as G-1, can improve lipid homeostasis, oxidative stress, and inflammation in adipocytes. The overall objective of this proposal is to understand the mechanisms of E2-mediated effects via GPER in metabolic regulation, specifically in adipocytes. The central hypothesis to be tested is whether GPER signaling directly improves lipid homeostasis, oxidative stress, inflammation, and mitochondrial function in adipocytes. These findings will inform drug development by making significant advancements in our knowledge regarding the role of GPER in obesity and lipid metabolism, ultimately advancing the current insufficient therapeutic treatment options available for obesity. The specific aims of this proposal are: Aim 1: Evaluate the roles of GPER in lipid metabolism of adipocytes. The working hypothesis for this aim is that GPER’s effects on obesity are in part mediated by direct actions on lipid metabolism on adipocytes. Aim 2: Determine the role of GPER in oxidative stress, inflammation, and mitochondrial function in adipocytes. The working hypothesis for this aim is that GPER plays a direct protective role against oxidative stress, inflammation, and improves mitochondrial function in adipocytes. This proposal will investigate the direct effects of GPER in adipocytes pertaining to lipid homeostasis, oxidative stress, inflammation, and mitochondrial function, with the potential to significantly advance the study of novel therapeutics protecting against obesity.


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: 2026 ( Subtotal = $19,869 )
2026	2026	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	4/3/2026	NON-COMPETING CONTINUATION	$96
2026	2026	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/25/2026	NON-COMPETING CONTINUATION	$19,773
														Subtotal = $19,869

Issue Date FY: 2025 ( Subtotal = $46,138 )
2025	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	7/14/2025	NON-COMPETING CONTINUATION	$46,138
2025	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	7/8/2025	OTHER REVISION	$0
2025	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/29/2025	TERMINATION	$0
														Subtotal = $46,138

Issue Date FY: 2024 ( Subtotal = $45,574 )
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/29/2024	NON-COMPETING CONTINUATION	$45,574
														Subtotal = $45,574

Issue Date FY: 2023 ( Subtotal = $44,294 )
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/8/2023	NEW	$44,294
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	3/14/2023	NEW	$0
														Subtotal = $44,294

Grand Total All Awards = $155,875

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Role of GPER in Obesity and Lipid Metabolism.

Award Number: F31DK136330

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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