# Impact of Shiftwork on Metabolic Flexibility and Skeletal Muscle Clocks

> **NIH NIH K01** · ADVENTHEALTH ORLANDO · 2024 · $157,334

## Abstract

PROJECT SUMMARY
Shiftwork is now recognized as a risk factor for type 2 diabetes (T2D); yet the mechanisms underlying these
associations are poorly understood. Addressing this knowledge gap requires converging the fields of metabolism
and chronobiology. T2D pathophysiology is characterized by both impaired metabolic flexibility and circadian
disruption, and skeletal muscle circadian clocks may be at the intersection of these features. Metabolic flexibility
is the capacity to efficiently switch between fuel sources and is largely maintained by skeletal muscle, whereas
metabolic inflexibility is implicated in insulin resistance (IR). Similarly, skeletal muscle clock disruption causes
insulin resistance in pre-clinical models and is associated with impaired glucose tolerance in humans.
Experimental simulations of short-term nightshift induce a prediabetic phenotype, indicating that the circadian
system plays a role in glucose metabolism. Herein, we will test the hypothesis that real-world nightshift work
impairs metabolic flexibility, and that this will be associated with disrupted skeletal muscle clocks. We will
conduct rigorously controlled in-patient studies to assess and compare whole-body metabolic flexibility using
innovative 24h metabolic chamber protocols, as well as diurnal shifts in skeletal muscle clock genes in dayshift
vs. nightshift workers. This NIH K01 Mentored Scientist Career Development Award was designed to enrich the
candidate’s research and training experiences, leading to an independent transdisciplinary research niche that
addresses the public health concerns of T2D risk in shift workers. The candidate will learn classic concepts in
metabolic flexibility and chronobiology from senior-level mentors and gain intensive training and hands-on
experience in cutting-edge methodologies: whole-room metabolic chambers, human skeletal muscle cell culture,
and clinical circadian protocols. The investigative team is uniquely positioned to address links between shiftwork,
metabolic inflexibility, and skeletal muscle clocks. AdventHealth’s Translational Research Institute (sponsoring
institution) houses a clinical research unit prepared for biospecimen collections, 4 state-of-the-art metabolic
chamber suits, and wet lab space dedicated to human skeletal muscle cell culture work. This project is a
collaborative effort with AdventHealth’s Nursing, Whole-Person, and Academic Research Group, who will
support recruitment through directly reaching ~1,500 local nurses working nightshift. These studies will
potentially shift the paradigm by identifying a metabolic defect specific to shiftwork that could be modified by
interventions targeting both insulin resistance and impaired fatty acid oxidation components of metabolic
flexibility across the 24h day-night cycle. At the conclusion of the funding period, the candidate will be well
equipped to pursue R-level funding. It is highly likely that exercise/physical activity interventions to mitigate or
p...

## Key facts

- **NIH application ID:** 10767355
- **Project number:** 5K01DK134838-02
- **Recipient organization:** ADVENTHEALTH ORLANDO
- **Principal Investigator:** Melissa Erickson
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $157,334
- **Award type:** 5
- **Project period:** 2023-01-23 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767355

## Citation

> US National Institutes of Health, RePORTER application 10767355, Impact of Shiftwork on Metabolic Flexibility and Skeletal Muscle Clocks (5K01DK134838-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10767355. Licensed CC0.

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