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The role of vagal afferent neurons in regulating feeding behavior

Award Number: R00DK094871
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: 05/01/2015
PERIOD OF PERFORMANCE END DATE: 04/30/2018

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The role of vagal afferent neurons in regulating feeding behavior - The vagus nerve has long been known to play a role in the regulation of food intake. The vagal afferent pathway senses hormones released from the gut in response to nutritional cues and relays these signals to the brain stem. We have recently demonstrated that vagal afferent neurons (VAN) can integrate these signals and alter expression of receptors and neuropeptide transmitters important in sensing and signalling, to modify feeding behavior. In obesity, the sensitivity of key receptors to their ligands are reduced in VAN, resulting in changes in the neurochemical phenotype of these neurons. Unfortunately the techniques currently available in the field do not allow manipulations of these neurons in vivo to determine the functional role of these proteins on feeding behavior. The overarching goal of this proposal will be to determine the role of the vagus nerve in regulating feeding behaviour with specific focus on understanding how dysregulation of vagal afferent signaling leads to the development of hyperphagia and weight gain in diet induced obesity. To achieve this goal we propose to 1) determine the role of the neuropeptide transmitters cocaine and amphetamine regulated transcript (CART), and melanin concentrating hormone (MCH) released from VAN into the brain stem in the regulation of feeding behavior under normal physiological conditions and their role in the progression of diet induced obesity, 2) the effect of leptin resistance in VAN on the progression of obesity, and 3) to use an intervention study targeting MCH and the leptin receptor downstream effector early growth response 1 (EGR-1) to prevent the onset of diet induced obesity. A key component of this proposal involves the development of a novel in vivo RNAi approach to target proteins expressed by VAN. The expected outcomes of this research proposal are to develop a novel in vivo RNAi approach to target proteins expressed by VAN and to demonstrate that this technique could be applied as a therapeutic tool in obesity as well as a research tool to elucidate the role of VAN. In addition, successful completion would demonstrate an important role for VAN in the development hyperphagia and weight gain; thereby identifying novel specific molecular targets for the treatment of 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: 2018 ( Subtotal = -$59 )
2018	2017	JOHN B. PIERCE LABORATORY, INC., THE	290 CONGRESS AVE	NEW HAVEN	CT	06519	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	8/23/2018	NON-COMPETING CONTINUATION	-$59
														Subtotal = -$59

Issue Date FY: 2017 ( Subtotal = $229,687 )
2017	2017	JOHN B. PIERCE LABORATORY, INC., THE	290 CONGRESS AVE	NEW HAVEN	CT	06519	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/24/2017	NON-COMPETING CONTINUATION	$206,718
2017	2017	JOHN B. PIERCE LABORATORY, INC., THE	290 CONGRESS AVE	NEW HAVEN	CT	06519	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	6/21/2017	NON-COMPETING CONTINUATION	$22,969
														Subtotal = $229,687

Issue Date FY: 2016 ( Subtotal = $239,560 )
2016	2016	JOHN B PIERCE FOUNDATION LABORATORY, INC	290 CONGRESS AVENUE	NEW HAVEN	CT	06519	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/21/2016	NON-COMPETING CONTINUATION	$239,560
														Subtotal = $239,560

Issue Date FY: 2015 ( Subtotal = $249,000 )
2015	2015	JOHN B PIERCE FOUNDATION LABORATORY, INC	290 CONGRESS AVENUE	NEW HAVEN	CT	06519	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/15/2015	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $718,188

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The role of vagal afferent neurons in regulating feeding behavior

Award Number: R00DK094871

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: 05/01/2015

PERIOD OF PERFORMANCE END DATE: 04/30/2018

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