Tuesday, April 16, 2024 4/16/2024

Peripheral Neurotrophic Factors in the Regulation of Adipose Tissue Energy Expenditure

Award Number: R01DK114320
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

In order to maintain proper energy balance and metabolic health, the body must tightly regulate the processes that control energy intake (appetite, food intake, nutrient absorption) as well as energy expenditure (physical activity, basal metabolism, thermogenesis). An important aspect of regulating energy expenditure is the transfer of signals from the brain through peripheral nerves to activate lipolysis and thermogenesis in white and brown adipose tissues, respectively. Cold-stimulation is able to increase the sympathetic innervation and activation of adipose tissues and thus increase energy expenditure through lipolysis and thermogenesis. The exact mechanisms by which cold (or other stimuli that increase energy expenditure) are able to mediate peripheral nerve plasticity are currently under-investigated and largely unclear. In the current project, we provide new evidence that white adipose tissue (WAT) undergoes increases in neural innervation after cold exposure or exercise in mice (plasticity), and reductions in neural innervation with aging or obesity/diabetes in mice and humans (neuropathy). In addition, we have demonstrated that adipose-resident immune cells are able to secrete the neurotrophic factor Brain Derived Neurotrophic Factor (BDNF), which we believe stimulates sympathetic nerve branching, neurite outgrowth, and synapse formation in order to stimulate energy-expending processes in adipose depots. Indeed, in models of adipose neuropathy such as aging, BDNF levels are significantly decreased in WAT. BDNF is well-studied in the brain, but has not been investigated for adipose tissue neurotrophic activity. We have found that BDNF is expressed in immune cells of the stromovascular fraction (SVF) of WAT, and that the secretion of BDNF increases after cold or noradrenergic stimulation. Deletion of BDNF from the myeloid lineage results in a striking and specific lack of neural innervation of adipose depots, without affecting other nerves in the brain, spinal column or neuromuscular junction. As a result of this `genetic denervation' we observed that the knock-out (KO) animals undergo a shift in energy balance that leads to increased adipose mass and lower energy expenditure, including a lack of UCP1 induction in WAT after cold exposure. We specifically hypothesize polarized macrophages in adipose tissue SVF act similarly to microglia in the brain – that is, they can be either immune cells that release nerve growth factors in response to injury or neuroplasticity needs, or they phagocytose neurites, leading to neuropathy. We have identified a population of macrophages we are calling cold-induced neuroimmune cells (CINCs) that we hypothesize secrete BDNF in response to cold/noradrenergic stimulation. In addition to investigating these mechanisms for adipose nerve plasticity and neuropathy, this project also seeks to better understand the types of nerves that innervate adipose as well as how proper innervation affects adipose tissue function, whole-body metabolism and the control of energy balance.


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: 2023 ( Subtotal = $0 )
2023	2019	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/5/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	UNIVERSITY OF MAINE SYSTEM	5717 CORBETT HALL RM 422	ORONO	ME	04469	PENOBSCOT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	9/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF MAINE SYSTEM	5717 CORBETT HALL RM 422	ORONO	ME	04469	PENOBSCOT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	8/27/2021	NON-COMPETING CONTINUATION	$0
2021	2019	UNIVERSITY OF MAINE SYSTEM	5717 CORBETT HALL RM 422	ORONO	ME	04469	PENOBSCOT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/25/2021	NON-COMPETING CONTINUATION	-$332,088
2021	2019	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	2/25/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$332,088
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $356,480 )
2019	2019	UNIVERSITY OF MAINE SYSTEM	5717 CORBETT HALL RM 422	ORONO	ME	04469	PENOBSCOT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/28/2019	NON-COMPETING CONTINUATION	$356,480
														Subtotal = $356,480

Issue Date FY: 2018 ( Subtotal = $356,480 )
2018	2018	UNIVERSITY OF MAINE SYSTEM	5717 CORBETT HALL RM 422	ORONO	ME	04469	PENOBSCOT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	7/4/2018	NEW	$20,569
2018	2018	UNIVERSITY OF MAINE SYSTEM	5717 CORBETT HALL RM 422	ORONO	ME	04469	PENOBSCOT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/7/2018	NEW	$335,911
														Subtotal = $356,480

Grand Total All Awards = $712,960

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Peripheral Neurotrophic Factors in the Regulation of Adipose Tissue Energy Expenditure

Award Number: R01DK114320

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer