# Brain-wide functional mapping of circuits controlling hedonic feeding in obesity

> **NIH NIH K01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $150,444

## Abstract

7. Project Summary:
The proposal describes a five-year plan for training Dr. Li Ye to achieve his goal to become an independent investigator in
the central regulation of metabolism. The training and career development plan includes a compelling research project,
training in laboratory techniques and didactic scientific and career development seminars and courses. The applicant has
more than a decade of experiences working in both molecular metabolism and systems neurosciences. During his Ph.D.,
Dr. Ye was trained with Dr. Bruce Spiegelman, a well-recognized leader in the field of obesity and diabetes. His previous
findings in metabolic research have been published in many high-impact journals and have been then cited near 4,000
times in the subsequent works of his peers. During the proposed training, Dr. Karl Deisseroth, a leading expert in
neurosciences will mentor the applicant’s scientific and career development. Dr. Deisseroth has trained numerous
prominent scientists who now hold faculty positions in academic institutions. In addition, an advisory committee with
highly regarded expertise in hypothalamic and feeding research (Dr. Luis de Lecea and Dr. Brad Lowell) will provide the
applicant scientific advice and career guidance.
The overall goal of the project is to study neural mechanisms responsible for coordinating food intake and metabolic
demands. The obesity epidemic is putting an enormous burden on the public health systems, by contributing to the
increased prevalence of type 2 diabetes, cardiovascular and neurodegenerative diseases. Obesity is a result of energy
imbalance, in which energy consumption chronically exceeds the expenditure. There are two types of feeding, one driven
by metabolic need and the other by the hedonic aspect of palatable food. The former is mainly regulated by the
hypothalamic and hindbrain structures that are responsive to peripheral hormonal signals such as leptin, insulin, and
ghrelin. The latter is predominantly controlled by the reward systems including the mesolimbic pathway and dopamine
signaling. Preliminary studies suggested these systems converge in the lateral hypothalamus area (LH). Dissecting the
circuit, cellular and molecular bases separating these two systems in the LH is key to understanding the central control of
energy balance and its dysfunction during obesity, however, differentiating intermingled neural ensembles within a brain
region has been difficult.
In his early postdoctoral work, the candidate has developed a series of CLARITY and optogenetics-based technologies
with sufficient throughput to map brain-wide connectivity as well as with the ability to retain molecular information at the
single cell level to distinguish intermingled neuronal populations. Using these tools, the candidate has successfully
dissected two anatomically intermingled but functionally distinct ensembles representing opposite valences in the medial
prefrontal cortex. These recent advances in systems neuroscience ...

## Key facts

- **NIH application ID:** 10197899
- **Project number:** 5K01DK114165-06
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Li Ye
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $150,444
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197899

## Citation

> US National Institutes of Health, RePORTER application 10197899, Brain-wide functional mapping of circuits controlling hedonic feeding in obesity (5K01DK114165-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10197899. Licensed CC0.

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