Wednesday, December 17, 2025 12/17/2025

Lipid metabolism and adipose tissue function

Award Number: R01DK130331
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Lipid metabolism and adipose tissue function - Project Summary The prevalence of obesity has increased worldwide to epidemic proportions. Dysfunctional white adipose tissue (WAT) and brown adipose tissue (BAT) have been implicated in the pathogenesis of obesity and its related metabolic syndrome. BAT is densely packed with mitochondria and requires fatty acid (FA) oxidation to support thermogenesis. In comparison, WAT serves as a main energy storage organ and the FA oxidation in WAT is relatively low at ambient temperature. Chronic cold exposure induces browning of subcutaneous WAT to become thermogenic beige AT with increased FA oxidation capacity. Although FA oxidation is known to be a critical and fundamental metabolic end point in both humans and rodents, it is not completely clear how adipocyte FA oxidation is regulated post-translationally and how it contributes to whole-body energy metabolism in an autonomous manner. In this regard, our preliminary studies provide compelling evidence that a protein encoded by Apolipoprotein 6 (ApoL6) is a selective regulator of mitochondrial trifunctional protein (TFP), the key enzyme catalyzing FA β-oxidation. ApoL6 is highly expressed in WAT and differentiated adipocytes. In contrast, BAT normally expresses low levels of ApoL6, which increases during obesity or thermoneutrality-induced whitening. We found that in the basal condition, ApoL6 is localized to mitochondria, resulting in attenuation of mitochondrial FA oxidation. Transgenic mice expressing ApoL6 in BAT exhibited a lower thermogenic capacity upon cold exposure, and decreased energy expenditure along with increased adiposity. Conversely, adipose ApoL6 knockout mice on HFD showed a decreased body weight and fat mass gain. Based on these preliminary data, we hypothesize that by inhibiting mitochondrial FA oxidation and thereby decreasing energy expenditure, ApoL6 plays a key role in (1) maintaining fat storage in WAT and whole-body energy balance, and (2) impeding non-shivering thermogenesis in whitened BAT. There are three aims: In aim 1, we will determine the mechanistic role of mitochondrially localized ApoL6 in adipocyte FA oxidation by using gain- and loss-of-function cell models. In Aim 2 we will determine how adipose specific ApoL6 ablation in mice affects diet-induced obesity and its related metabolic changes including insulin resistance. In Aim 3 we will use both loss- and gain-of-function mouse models to define the role of ApoL6 in the regulation of BAT thermogenesis during obesity- and thermoneutrality-induced whitening. Evidence derived from this project should provide novel insight into the molecular basis for the regulation of FA oxidation and energy metabolism in adipose tissue, thereby advancing the possibilities for the development of novel therapeutic approaches to combat obesity and type 2 diabetes.


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 = $0 )
2026	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	10/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $504,905 )
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/22/2024	NON-COMPETING CONTINUATION	$454,414
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	6/13/2025	NON-COMPETING CONTINUATION	$50,491
														Subtotal = $504,905

Issue Date FY: 2024 ( Subtotal = $484,709 )
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/29/2023	NON-COMPETING CONTINUATION	$454,414
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/17/2024	NON-COMPETING CONTINUATION	$30,295
														Subtotal = $484,709

Issue Date FY: 2023 ( Subtotal = $504,905 )
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/2/2023	NON-COMPETING CONTINUATION	$50,491
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/30/2022	NON-COMPETING CONTINUATION	$454,414
														Subtotal = $504,905

Issue Date FY: 2022 ( Subtotal = $504,905 )
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/25/2021	NEW	$504,905
														Subtotal = $504,905

Grand Total All Awards = $1,999,424

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Lipid metabolism and adipose tissue function

Award Number: R01DK130331

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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