# JARID1a in circadian control of hepatic energy metabolism

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $344,250

## Abstract

PROJECT SUMMARY
In mammals, the circadian oscillator has emerged as a critical orchestrator of metabolism and energy
homeostasis. Importantly, circadian dysfunction due to environmental factors commonly found in modern
lifestyles (jet lag, rotating shift work, artificially-extended photoperiod, western diets) has been linked to weight
gain, metabolic syndrome, and diabetes. An important connection between the circadian clock and energy
metabolism occurs at the level of epigenetic control. However, how the clock bears upon genomic regulation of
energy homeostasis through epigenetic mechanisms is not fully understood. In particular, the effects that
chronodisruption and western-style diets have on the function of epigenetic regulators and the mechanisms by
which they, in turn, contribute to the development of metabolic disease remains unknown. We previously
described the JmjC-class lysine demethylase JARID1a as a non-redundant component of the circadian oscillator.
Recently, we have observed that liver-specific ablation of JARID1a results in disruptions to glucose metabolism.
This proposal uses a combination of novel tissue-specific genetic murine models, light-dark schedule and dietary
manipulations, molecular biology techniques, and genomic approaches to characterize JARID1a as a novel
epigenetic link between chronodisruptive environmental variables and metabolic dysfunction. Based on
preliminary data, this proposal tests the central hypothesis that JARID1a is an epigenetic link between the
circadian clock and genomic regulation of glucose metabolism through opposing modulation of the transcription
factors CREB and ChREBP, and whose dysfunction disrupts glucose homeostasis. In our first aim, we
interrogate the impact of a high-fat diet, fatty acids, fasting, acute feeding, chronodisrupted light schedules, and
metabolic signaling pathways on JARID1a function. In our second aim, we investigate the molecular mechanisms
by which JARID1a regulates energy metabolism through opposing control of two important regulators of glucose
homeostasis: the transcription factors CREB and ChREBP.

## Key facts

- **NIH application ID:** 9969406
- **Project number:** 5R01DK108088-05
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Luciano DiTacchio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,250
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969406

## Citation

> US National Institutes of Health, RePORTER application 9969406, JARID1a in circadian control of hepatic energy metabolism (5R01DK108088-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9969406. Licensed CC0.

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