Novel CNS mechanisms to combat obesity
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
Summary Obesity is characterized by visceral fat accrual and lipid spillover to liver and heart, driven largely by systemic insulin resistance. Key drivers of obesity are excessive feeding and reduced energy expenditure. Consequently, understanding the mechanisms that control feeding and/or energy expenditure will help develop strategies to combat obesity and metabolic diseases. At the whole organismal level, the central nervous system (CNS), in particular the hypothalamus and hindbrain, sense signals of nutrient availability and coordinate energy metabolism. While cell-types in the arcuate and their functions are well-characterized, how different cell-types and neuronal populations in the paraventricular nucleus of the hypothalamus (PVH), a deep-seated region in the hypothalamus, coordinate peripheral energy metabolism remains poorly studied. In particular, it is unclear how the PVH integrates physiological nutrient-related cues to control peripheral energy and lipid metabolism, and how these processes are disrupted to cause obesity and insulin resistance. My studies using brain-wide imaging of c-Fos, a defined neuron activation marker, revealed that dietary triglycerides administered via an oral gavage activates diverse regions across the brain, with greatest activation in discrete regions of the hypothalamus, including the PVH. Comparative bulk-RNA sequencing of multiple regions with the greatest response to lipids revealed Zinc Finger and BTB Domain Containing 16, a transcription factor required for stem cell maintenance and cell differentiation, as a key ubiquitously upregulated gene in response to corn oil gavage, including the PVH. Based on hypothalamic single-nuclei RNA sequencing, and PVH spatial transcriptomics, we reveal that this lipid-driven induction of ZBTB16 expression occurs in a small cluster of a poorly-characterized PVH neurons. On this basis, I hypothesize that these lipid-responsive PVH neurons play a role in regulating systemic lipid metabolism. Consistently, my preliminary studies in a small group of mice revealed that deletion of ZBTB16 in these PVH neurons leads to weight gain and adiposity when compared to controls. Taken together, in this K01 Mentored Research Scientist Career Development Award, I will test the hypothesis that lipid-driven induction of ZBTB16 in these novel PVH neurons facilitates energy expenditure in peripheral fat depots and maintains energy balance; and that sustained high fat diet feeding alters the activity of these neurons to cause obesity. I will test this hypothesis via three specific aims: Aim 1 will characterize the changes that occur in these poorly studied PVH neurons as mice transition from lean to obesity states; Aim 2 will determine the role of ZBTB16 in PVH neurons in the pathophysiology of obesity; while Aim 3 will evaluate the effect of stimulation of these PVH neurons on the reversal of obesity phenotypes. I expect that the completion of these studies will not only reveal novel roles of an uncharacterized neuronal population in combating obesity, but this K01 grant will also serve as a critical mechanism for my career development into an independent neuroscience-focused obesity researcher.
Grant Summary
Novel CNS mechanisms to combat obesity is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $167K for university, nonprofit, healthcare org. Applications are due 2031-02-28 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $167K
2031-02-28
- 1Confirm your organization is eligible for Novel CNS mechanisms to combat obesity from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases before the deadline.
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Novel CNS mechanisms to combat obesity: Frequently Asked Questions
Who is eligible for the Novel CNS mechanisms to combat obesity?
Novel CNS mechanisms to combat obesity is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Novel CNS mechanisms to combat obesity provide?
Novel CNS mechanisms to combat obesity provides up to $167K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Novel CNS mechanisms to combat obesity deadline?
Applications for Novel CNS mechanisms to combat obesity are due 2031-02-28 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Novel CNS mechanisms to combat obesity?
To apply for Novel CNS mechanisms to combat obesity, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.