# Brain-wide functional mapping of circuits controlling hedonic feeding in obesity > **NIH NIH K01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $75,222 ## Abstract Project Summary: The proposal describes a five-year plan with a one-year extension for training Dr. Li Ye to achieve his goal to become an independent investigator in the central regulation of metabolism. The training plan includes a compelling research project, training in laboratory techniques, didactic scientific and career development courses. The applicant has more than a decade of experiences working in both metabolism and systems neurosciences. Dr. Ye’s previous findings in metabolic research have been published in many high- impact journals and have been then cited near 6,000 times by his peers. During the proposed training, Dr. Karl Deisseroth and Dr. Hollies Cline, leading experts in neurosciences will mentor the applicant’s scientific and career development. A committee with expertise in hypothalamic research (Dr. Luis de Lecea and Dr. Brad Lowell) will provide further scientific and career guidance. The goal of the project is to study neural mechanisms coordinating food intake and metabolic demands. Obesity is a result of energy imbalance, in which energy consumption exceeds the expenditure. Food intake can be driven by metabolic need or the hedonic value of palatable food. The former is mainly regulated by the hypothalamic structures that are responsive to hormonal signals. The latter is largely controlled by the mesolimbic reward systems. Preliminary studies suggested these systems converge in the lateral hypothalamus area (LH). Dissecting the circuit, cellular and molecular bases separating these two systems is key to understanding the central control of energy balance and its dysfunction during obesity, however, differentiating intermingled neural ensembles has been difficult. The candidate has developed a series of CLARITY and optogenetics-based technologies with sufficient throughput to map brain-wide connectivity and with the ability to retain molecular information to distinguish intermingled neuronal populations. The candidate has successfully dissected two anatomically intermingled but functionally distinct ensembles representing opposite valences in the prefrontal cortex. Thus, these systems provide us a unique opportunity to dissect the LH ensembles recruited by hedonic vs. metabolic feeding. The central hypothesis is that hedonic and metabolic feeding recruit distinct LH ensembles. Specifically, these ensembles quantitatively differ in: (1) the inputs they receive from upstream regions, (2) activity during different types of feeding, and (3) causal impact on feeding. The adaptation of these ensembles to diet is key to the development of hyperphagia. The approach is to use neuroscience tools to monitor and manipulate neural activity in animals (Aim 1&2). The circuit adaption will be measured using ribosome-profiling and imaging approaches (Aim3). Together, this study will elucidate neural mechanisms underlying the HFD-induced hyperphagia and provide the candidate with the training to start an independent research program fo... ## Key facts - **NIH application ID:** 10434601 - **Project number:** 3K01DK114165-06S1 - **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:** $75,222 - **Award type:** 3 - **Project period:** 2017-07-01 → 2022-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10434601 ## Citation > US National Institutes of Health, RePORTER application 10434601, Brain-wide functional mapping of circuits controlling hedonic feeding in obesity (3K01DK114165-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434601. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*