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Adiponectin, A Protein Secreted From Adipose Tissue

Award Number: R01DK055758
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: 05/15/2000
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Adiponectin, A Protein Secreted From Adipose Tissue - Adipocytes are professional secretory cells. Many adipose tissue-secreted signaling mediators (adipokines) have been identified since the discovery of leptin and adiponectin. As such, much has been learned about how adipose tissue communicates with other organs of the body to maintain systemic homeostasis. Beyond proteins, additional factors such as lipids, metabolites, non-coding RNAs and extracellular vesicles released by adipose tissue participate in this process. However, major gaps still persist in our basic understanding of how leptin and adiponectin achieve their profound actions on target cells. In this renewal application, we focus on adiponectin, a protein we first described in 1995. The previous funding period has shed much light on how adiponectin and its receptors achieve anti-inflammatory, anti-apoptotic and insulin sensitizing effects through the ceramide axis, primarily through gain-of-function approaches. In the proposed studies in this application, we aim to elucidate why adiponectin knock out models generated by different groups give rise to seemingly different metabolic phenotypes. In preliminary studies, we attribute this phenomenon to different strategies for gene elimination. While our own knock out mouse completely lacks all relevant exons for the adiponectin gene, other models leave behind exon 3 that has the potential to encode a non-secreted form of globular adiponectin. We believe it is this remnant fragment that is responsible for the different phenotypes. Furthermore, we believe that endogenous adiponectin, even in the absence of any gene manipulation, may also have a non-secreted, cytoplasmic / nuclear form that exerts unique functions locally in adiponectin expressing cells. In fact, adiponectin is expressed in the proximal tubules of the kidney, specifically in the cortex. We show that adiponectin exerts a major role on renal gluconeogenesis. Adiponectin is also expressed in hepatic stellate cells, where it prevents the activation of stellate cells into fibrotic myofibroblasts. Inducible gain- and loss-of-function experiments will shed more light on the relevance of these phenomena. Finally, we are well positioned to eliminate both adiponectin receptors inducibly in target cells in the adult animal. This has not been possible so far due to embryonic lethality of double-knock out animals. We will focus our efforts initially on the hepatocyte and the adipocyte, in which we will inducibly eliminate both adiponectin receptors. Combined, these experiments will significantly broaden our knowledge of adiponectin function in “non-conventional” areas of metabolism studies. “Non-conventional” in the sense of adiponectin expression in cells other than adipocytes. Furthermore, “non-conventional” in the sense of adiponectin action not mediated through its passing through the secretory pathway, but rather through its actions as a non-secreted fragment in the cytoplasm and/or nucleus. Particularly the latter efforts have been inspired by studies in the various adiponectin knock out models, which have given rise to a large amount of confusing and discrepant data that we aim to explain and clarify for the field.


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	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	25	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $516,403 )
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	25	8/27/2024	NON-COMPETING CONTINUATION	$516,403
														Subtotal = $516,403

Issue Date FY: 2023 ( Subtotal = $537,920 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	24	8/30/2023	NON-COMPETING CONTINUATION	$537,920
														Subtotal = $537,920

Issue Date FY: 2022 ( Subtotal = $537,920 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	8/30/2022	NON-COMPETING CONTINUATION	$537,920
														Subtotal = $537,920

Issue Date FY: 2021 ( Subtotal = $537,920 )
2021	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	22	8/30/2021	NON-COMPETING CONTINUATION	$537,920
2021	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	21	6/24/2021	COMPETING CONTINUATION	$3,817
2021	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	6/24/2021	NON-COMPETING CONTINUATION	-$3,817
														Subtotal = $537,920

Issue Date FY: 2020 ( Subtotal = $536,280 )
2020	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	21	3/5/2020	COMPETING CONTINUATION	$536,280
														Subtotal = $536,280

Issue Date FY: 2019 ( Subtotal = $448,376 )
2019	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	8/15/2019	NON-COMPETING CONTINUATION	$448,376
														Subtotal = $448,376

Issue Date FY: 2018 ( Subtotal = $448,376 )
2018	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	8/21/2018	NON-COMPETING CONTINUATION	$448,376
														Subtotal = $448,376

Issue Date FY: 2017 ( Subtotal = $302,577 )
2017	2017	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	18	8/30/2017	NON-COMPETING CONTINUATION	$448,376
2017	2016	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	8/29/2017	SUPPLEMENT FOR EXPANSION	-$145,799
														Subtotal = $302,577

Issue Date FY: 2016 ( Subtotal = $594,176 )
2016	2016	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	17	9/1/2016	SUPPLEMENT FOR EXPANSION	$145,800
2016	2016	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	8/30/2016	NON-COMPETING CONTINUATION	$448,376
														Subtotal = $594,176

Issue Date FY: 2015 ( Subtotal = $446,992 )
2015	2015	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	16	9/23/2015	COMPETING CONTINUATION	$446,992
														Subtotal = $446,992

Issue Date FY: 2014 ( Subtotal = $432,393 )
2014	2014	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	5/5/2014	NON-COMPETING CONTINUATION	$432,393
														Subtotal = $432,393

Issue Date FY: 2013 ( Subtotal = $417,259 )
2013	2013	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	5/22/2013	NON-COMPETING CONTINUATION	$417,259
														Subtotal = $417,259

Issue Date FY: 2012 ( Subtotal = $431,939 )
2012	2012	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	4/19/2012	NON-COMPETING CONTINUATION	$431,939
														Subtotal = $431,939

Issue Date FY: 2011 ( Subtotal = $553,398 )
2011	2011	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	12	6/17/2011	SUPPLEMENT FOR EXPANSION	$122,362
2011	2011	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	6/14/2011	NON-COMPETING CONTINUATION	$431,036
														Subtotal = $553,398

Issue Date FY: 2010 ( Subtotal = $518,937 )
2010	2010	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	11	4/22/2010	COMPETING CONTINUATION	$4,911
2010	2010	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	11	4/13/2010	COMPETING CONTINUATION	$514,026
2010	2010	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	11	5/3/2010	COMPETING CONTINUATION	$0
2010	2009	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	10	4/30/2010	NON-COMPETING CONTINUATION	$0
2010	2009	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	4/9/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $518,937

Issue Date FY: 2009 ( Subtotal = $421,212 )
2009	2009	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	4/23/2009	NON-COMPETING CONTINUATION	$421,212
														Subtotal = $421,212

Issue Date FY: 2008 ( Subtotal = $409,002 )
2008	2008	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	4/14/2008	NON-COMPETING CONTINUATION	$409,002
														Subtotal = $409,002

Issue Date FY: 2007 ( Subtotal = $405,256 )
2007	2007	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	6/7/2007	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$405,256
														Subtotal = $405,256

Issue Date FY: 2006 ( Subtotal = $428,067 )
2006	2006	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	5/1/2006	NON-COMPETING CONTINUATION	$428,067
														Subtotal = $428,067

Issue Date FY: 2005 ( Subtotal = $435,498 ) (Continued on the next page)
Grand Total All Awards = $10,925,382

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Adiponectin, A Protein Secreted From Adipose Tissue

Award Number: R01DK055758

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: 05/15/2000

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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