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

The impact of dietary fatty acids and TNF-alpha on neuropathy associated with metabolic syndrome

Award Number: R01DK149012
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: 08/28/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

Group Awards By:

View Award Description

The impact of dietary fatty acids and TNF-alpha on neuropathy associated with metabolic syndrome - Abstract Peripheral neuropathy (PN) is a common complication of diabetes, prediabetes, and the metabolic syndrome. PN causes a progressive decrease in sensory function resulting in severe morbidity characterized by loss of sensation, poor balance, and can eventually lead to amputation of the effected limb. Despite the prevalence and debilitating nature of this neurological complication, there is currently no disease-modifying treatment, and the molecular mechanisms that underlie PN in the metabolic syndrome are incompletely understood. Mice fed a high-fat diet rich in saturated fatty acids develop both the metabolic syndrome and PN similar to their human counterparts. We recently discovered that switching these mice from a high-fat diet enriched with saturated fatty acids to a high-fat diet enriched with monounsaturated fatty acids significantly improved nerve function without affecting metabolic impairments. These results indicate that dietary saturated and monounsaturated fatty acids differentially regulate nerve function in the context of the metabolic syndrome. To identify novel therapeutic targets for metabolic syndrome PN, it is important to understand the cell type-specific changes that underlie PN pathogenesis. The metabolic syndrome is often linked to chronic inflammation that impacts a multitude of tissues and alters lipid metabolism and energy homeostasis. Saturated fatty acids have generally been associated with pro-inflammatory pathways, whereas monounsaturated fatty acids reduce inflammation. However, specific inflammatory factors and downstream alterations in lipid metabolism and energy homeostasis by these fatty acids in the peripheral nerves is not known. Herein, we hypothesize that saturated fatty acids induce neuroinflammation and toxic lipid metabolism pathways, while dietary monounsaturated fatty acids reverse the aberrant pathways thereby restoring nerve function. We will test these hypotheses by 1) identifying cell-specific changes in lipid metabolism that underlie PN 2) determine the resident or infiltrating inflammatory cells that contribute to PN progression during the metabolic syndrome, and 3) assess the role of tumor necrosis factor  (TNF) and neutral sphingomyelinase, an enzyme that hydrolyzes sphingomyelin, as a central lipid metabolism mediator that connects inflammation with lipid metabolism to regulate nerve function in mice with metabolic syndrome PN. Altogether, these studies will determine the specific lipid metabolism and inflammatory pathways that underlie PN as well as the molecular changes that drive the beneficial effect of monounsaturated fatty acids. Successful completion of these studies will greatly enhance our understanding of the molecular pathways that impact nerve function in metabolic syndrome and provide specific therapeutic targets for PN.


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 = $798,942 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/28/2026	NEW	$798,942
														Subtotal = $798,942

Grand Total All Awards = $798,942

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The impact of dietary fatty acids and TNF-alpha on neuropathy associated with metabolic syndrome

Award Number: R01DK149012

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: 08/28/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer