Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Leptin transport in the choroid plexus and tanycytes

Award Number: R01DK148663
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: 09/15/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2030

Group Awards By:

View Award Description

Leptin transport in the choroid plexus and tanycytes - Project Summary/Abstract Leptin is an adipocyte-derived hormone that regulates appetite, energy expenditure, and glucose metabolism. In obesity, central leptin resistance develops when high circulating leptin levels fail to activate hypothalamic neurons. Despite decades of research on leptin action, the cellular mechanisms by which leptin enters the brain remain poorly understood, which limits strategies to restore leptin sensitivity in obesity-linked metabolic diseases. Our preliminary findings identify the choroid plexus (ChP) and hypothalamic tanycytes as specialized cellular gateways that play a role in the transport of leptin. We discovered that in ChP epithelial cells, low-density lipoprotein receptor-related protein-1 (LRP1) forms a functional complex with the leptin receptor (LepR) to mediate receptor-dependent transcytosis of leptin from circulation to the brain. Deletion of LRP1 or LepR in ChP cells impairs hypothalamic STAT3 activation and increases food intake, leading to obesity. Importantly, the LRP1–LepR complex is disrupted in diet-induced obesity, suggesting a pivotal role for this complex in leptin resistance. In parallel, our previous work demonstrates that tanycytic LepR forms a complex with EGFR to promote leptin uptake into the hypothalamus. We hypothesize that the LRP1–LepRa complex in the ChP and the EGFR–LepRa complex in tanycytes are critical molecular gateways for leptin entry into the brain, and their disruption contributes to central leptin deficiency, causing obesity. In this grant, we propose three aims: (i) determine the functional importance of LRP1 in ChP-mediated leptin transport and energy balance; (ii) elucidate the isoform-specific role of LepRa in ChP leptin transcytosis and diet-induced obesity; and (iii) define the physiological role of tanycytic LepRa in leptin transport, central leptin sensitivity, and glucose metabolism. These aims will be addressed using state-of-the-art tools, including Cre-dependent genetic models, AAV-DIO systems, tanycytes engineering, human ChP-derived epithelial cells, and advanced metabolic assays. This work will uncover a new mechanism for how leptin gains access to the brain via the ChP and tanycytes, providing insights into the etiopathogenesis of obesity. These findings may identify novel therapeutic strategies to restore leptin sensitivity in obesity and related metabolic 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: 2026 ( Subtotal = $876,947 )
2026	2026	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/11/2026	NEW	$876,947
														Subtotal = $876,947

Grand Total All Awards = $876,947

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Leptin transport in the choroid plexus and tanycytes

Award Number: R01DK148663

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: 09/15/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer