Research | Hepler Lab
Our Work
Learn more about the Hepler Lab's work and impact.
Adipose tissue plays a central role in maintaining metabolic health by storing excess nutrients and releasing fuels during fasting. However, during obesity and aging this system often fails, leading to inflammation, insulin resistance, and metabolic disease.
Our laboratory investigates how circadian clocks coordinate metabolism in adipose tissue and across organs to preserve metabolic flexibility.
We focus on three major questions:
How does the timing of food intake reshape metabolic pathways across tissues?
How do circadian clocks regulate inflammation in adipose tissue?
How does mitochondrial dysfunction trigger maladaptive adipose remodeling during obesity?
When food is consumed strongly influences how nutrients are processed. Restricting food intake to the active phase of the day through interventions such as time-restricted eating or caloric restriction improves metabolic health across species. Despite the growing popularity of these approaches, the metabolic mechanisms that drive their benefits remain poorly understood.
Our laboratory studies how circadian dietary interventions reshape metabolic flux across tissues. Using stable isotope tracing and metabolomics, we investigate how aligning food intake with circadian rhythms reorganizes nutrient utilization, mitochondrial metabolism, and inter-organ metabolic communication. These studies aim to uncover the metabolic pathways through which feeding-time alignment improves insulin sensitivity, promotes metabolic flexibility, and supports healthy aging.
A hallmark of obesity and aging is the development of chronic low-grade inflammation in visceral adipose tissue. This inflammatory state disrupts adipocyte metabolism and contributes to systemic insulin resistance. Our work investigates how the circadian clock restrains inflammatory signaling within adipocytes.
We focus on how circadian transcriptional repressors regulate inflammatory pathways and coordinate interactions between adipocytes and immune cells. By defining how circadian clocks suppress inflammatory programs in adipose tissue, we aim to understand why circadian disruption accelerates metabolic disease and to identify strategies to restore metabolic health during obesity and aging.
Adipose tissue must remodel continuously to safely store excess nutrients. During overnutrition, this remodeling can remain adaptive through adipocyte hyperplasia or become pathological through adipocyte hypertrophy, leading to fibrosis, inflammation, and lipid spillover into other organs. Our research shows that mitochondrial function is an early determinant of adipose tissue remodeling.
Circadian disruption and nutrient excess impair mitochondrial electron transport in adipocytes, activating stress pathways that alter transcriptional identity and metabolic function. We study how defects in specific mitochondrial respiratory complexes trigger maladaptive remodeling and how restoring mitochondrial metabolism preserves adipose tissue function. These studies aim to reveal fundamental mechanisms linking mitochondrial metabolism, circadian timing, and adipose tissue plasticity during obesity.
