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The dorsomedial hypothalamus integrates temperature and energy sensing signals to regulate energy expenditure.

Award Number: F32DK132863
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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ABSTRACT The two primary factors that drive changes in body weight (BW) - food intake (FI) and energy expenditure (EE) - are both regulated within the hypothalamus of the brain and respond to changes in energy availability (energy-sensing) and ambient temperature (temperature-sensing). A more comprehensive understanding of how the hypothalamus regulates food intake and energy expenditure can enhance our approach to treating obesity through a pharmaceutical and/or environmental approach that targets the relevant neurons and/or environmental strategies that promote high EE and lower FI. Research outlined in this proposal seeks to describe how temperature and energy-sensing circuits integrate with each other. Proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in the arcuate nucleus (ARC) are known to regulate FI via MC4R signaling in the paraventricular nucleus (PVN), but the PVN does not account for EE regulation in response to feeding signals (2). An article investigating Gsα deficiency in the DMH revealed that DMH-specific MC4R knockout impairs EE and resulted in BW increases without impacting FI, implying that energy-sensing signals from the ARC affect EE adaptations via the DMH (3). Our hypothesis is that the DMH is an integration site of thermoregulatory and energy-sensing signals that impact EE. Activation of warm-sensitive neurons of the preoptic area suppresses EE in response to warm temperatures, and this is traditionally thought to occur via the inhibition of cold-sensitive neurons in the DMH that promote brown adipose tissue (BAT) thermogenesis despite the recent discovery that warm sensitive POA neurons are glutamatergic (6). Additionally, the POA projects directly to sympathetic pre-motor neurons in the raphe pallidus (RPa), and it is unclear what distinctive roles the POA-DMH and POA-RPa connection play in EE regulation (5). We hypothesize that the POA-DMH connection is a critical integrator for temperature and energy state EE adaptations, while the POA-RPa might mediate only temperature-dependent EE adaptations and could bypass feeding-induced MC4R signaling in the DMH. Using optogenetics and a novel strategy known as synthetic-and-physiological- activation-assisted-circuit-mapping (SPAACM), we will investigate how the POA, DMH, RPa, and ARC interact with each other and control EE in response to changes in ambient temperature and feeding states. SPECIFIC AIM I investigates the role of energy-sensing signals in the DMH and whether there is a temperature- dependent effect on EE within this circuit. SPECIFIC AIM II focuses on the POA>DMH and POA>RPa connections and their respective contributions to thermoregulatory modulation of EE.


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: 2024 ( Subtotal = -$100,861 )
2024	2023	LSU PENNINGTON	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/26/2024	NON-COMPETING CONTINUATION	-$76,500
2024	2022	LSU PENNINGTON	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	7/24/2024	NEW	-$19,816
2024	2022	LSU PENNINGTON	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	7/4/2024	NEW	-$4,545
														Subtotal = -$100,861

Issue Date FY: 2023 ( Subtotal = $76,500 )
2023	2023	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	5/10/2023	NON-COMPETING CONTINUATION	$76,500
														Subtotal = $76,500

Issue Date FY: 2022 ( Subtotal = $74,174 )
2022	2022	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	5/2/2022	NEW	$0
2022	2022	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	7/14/2022	NEW	-$3
2022	2022	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/2/2022	NEW	$74,177
														Subtotal = $74,174

Grand Total All Awards = $49,813

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The dorsomedial hypothalamus integrates temperature and energy sensing signals to regulate energy expenditure.

Award Number: F32DK132863

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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