About

Andrea Hevener is a Professor-in-Residence in the Department of Medicine at UCLA. She holds a PhD in Kinesiology, Physiology & Biophysics from the University of Southern California and a BS in Sports Medicine from Pepperdine University. Her research focuses on the molecular and cellular mechanisms underlying metabolic health, with particular attention to mitochondrial function, hormone receptor interactions, and tissue communication during exercise. She has held the Sidney Roberts and Clara Szego Roberts Endowed Chair in Molecular/Cellular Endocrinology from 2019 to 2024. Her work investigates sex-specific mechanisms of gene regulation, the impact of exercise on inter-organ endocrine networks, and the role of estrogen receptors in metabolic resilience. Dr. Hevener's research has contributed to understanding how endurance training remodels metabolic pathways and how sex differences influence molecular adaptations in tissues such as liver and skeletal muscle.

Research topics

• Medicine
• Internal medicine
• Endocrinology
• Genetics
• Biology
• Bioinformatics
• Physical medicine and rehabilitation

Selected publications

• Drp1 regulates mitochondrial health and controls skeletal muscle mass through the Erk1/2-Nur77 pathway

  Science Advances · 2026-05-08

  articleOpen access

  The maintenance of skeletal muscle mass relies on mitochondrial quality control, including balanced dynamics and mitophagy. Dynamin-related protein 1 (Drp1), a central mediator of mitochondrial fission, is essential for these processes, yet its role in muscle mass regulation remains incompletely defined. Here, we show that acute Drp1 deletion in the skeletal muscle increases Parkin-mediated mitochondrial degradation, reduces mitochondrial DNA (mtDNA) content, and leads to severe muscle atrophy. Although dual deletion of Drp1 and Parkin restores mtDNA content, muscle loss persists. Mechanistically, Drp1 loss impairs mitochondrial respiratory chain activity, suppressing extracellular signal-regulated kinase 1/2 (Erk1/2) signaling and down-regulating the nuclear receptor subfamily 4 group A member 1 (Nur77). Pharmacologic β2-adrenergic receptor activation with clenbuterol reactivated Erk1/2, restored Nur77 expression, and rescued muscle atrophy. These findings define a Drp1-Erk1/2-Nur77 signaling axis linking mitochondrial integrity to skeletal muscle mass and identify a potential therapeutic target for muscle degeneration in mitochondrial and metabolic diseases.

  PublisherDOI

• Multi-omic identification of key transcriptional regulatory programs during endurance exercise training in rats

  Nature Communications · 2026-03-21

  articleOpen access

  Transcription factors play a key role in regulating gene expression. We conduct an integrated analysis of chromatin accessibility, DNA methylation, mRNA expression, protein abundance and phosphorylation across eight tissues in fifty rats of equally represented sexes following endurance exercise training to identify coordinated epigenomic and transcriptional changes and determine key transcription factors involved. We uncover tissue-specific endurance exercise training associated changes and transcription factor motif enrichment across differentially expressed genes, accessible regions, and methylated regions. We discover distinct routes of training-induced regulation through either epigenomic alterations providing better access for transcription factors to affect target genes, or via changes in transcription factor expression or activity enabling target gene responses. We identify transcription factor motifs enriched among correlated epigenomic and transcriptomic alterations, differentially expressed genes correlated with exercise-related phenotypic and cell type composition changes, and training-induced activity changes of transcription factors whose target genes are enriched for differentially expressed genes. This analysis elucidates the unique gene regulatory mechanisms mediating diverse transcriptional responses to training across tissues.

  PublisherDOI

• Temporal Multi-Omic Analysis Uncovers Sex-Biased Molecular Programs Underlying Skeletal Muscle Adaptation to Endurance Training

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-27

  articleOpen access

  Background: Exercise training is known to benefit health and reduce disease risk. While skeletal muscle adaptations are fundamental to many of the health benefits of exercise training, the common and sex-specific molecular regulators that mediate these adaptations remain to be fully elucidated. Methods: To this end, we leveraged skeletal muscle multi-omics data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), where 6 month-old male and female rats endurance trained for 1, 2, 4, or 8 weeks. Our objective was to identify shared and sex-specific multi-omic molecular responses to endurance training in skeletal muscle, and relate them to phenotypic adaptations. Results: , which correlated with skeletal muscle responses from a published exercise study in humans. We uncovered sex-consistent post-translational modifications, including decreased oxidation of MYH2 and deacetylation of the β-oxidation enzyme HADHA. Pathway enrichment analyses revealed sex-specific remodeling across the acetylome, redox proteome, and phosphoproteome; females decreased mitochondrial protein cysteine oxidation and increased mitochondrial cristae proteins, indicative of enhanced redox buffering and mitochondrial efficiency. Despite decreases in cysteine oxidation of key mitochondrial proteins, females displayed increases in the cysteine oxidation of proteins involved in glucose catabolism relative to males after 8 weeks of training, suggestive of sex-biased subcellular reactive oxygen species generation. Males demonstrated earlier induction of mitochondrial transcripts and predicted activation of mTOR. Although the increase in mitochondrial protein abundance was more modest in males, there was greater oxidation of mitochondrial proteins in response to training compared to females. Conclusions: This work shows a large portion of the adaptive response to endurance training in skeletal muscle is shared between females and males, while there are distinct and nuanced sex-specific adaptations that are evident, particularly at the level of post-translational regulation.

  PublisherOA PDFDOI

• Muscle metabolic resilience and enhanced exercise adaptation by Esr1-induced remodeling of mitochondrial cristae-nucleoid architecture in males

  Cell Reports Medicine · 2025-05-01 · 7 citations

  articleOpen accessSenior author

  Reduced estrogen action is associated with obesity and insulin resistance. However, the cell and tissue-specific actions of estradiol in maintaining metabolic health remain inadequately understood, especially in men. We observed that skeletal muscle ESR1/Esr1 (encodes estrogen receptor α [ERα]) is positively correlated with insulin sensitivity and metabolic health in humans and mice. Because skeletal muscle is a primary tissue involved in oxidative metabolism and insulin sensitivity, we generated muscle-selective Esr1 loss- and gain-of-expression mouse models. We determined that Esr1 links mitochondrial DNA replication and cristae-nucleoid architecture with metabolic function and insulin action in the skeletal muscle of male mice. Overexpression of human ERα in muscle protected male mice from diet-induced disruption of metabolic health and enhanced mitochondrial adaptation to exercise training intervention. Our findings indicate that muscle expression of Esr1 is critical for the maintenance of mitochondrial function and metabolic health in males and that tissue-selective activation of ERα can be leveraged to combat metabolic-related diseases in both sexes.

  PublisherOA PDFDOI

• Endurance exercise drives temporal and sexual dimorphic multi-omic adaptations in liver metabolism-Findings from MoTrPAC

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-19

  preprintOpen access

  The mechanisms by which exercise modulate liver metabolism, a central regulator of systemic metabolism, are poorly understood. Leveraging data from MoTrPAC, we analyzed liver adaptations across 1, 2, 4, and 8 weeks of exercise in male and female rats using multi-omic approaches. Female livers displayed a progressive increase in oxidative phosphorylation (OXPHOS) complexes (at the protein level), while male livers showed an increase in acetylation of OXPHOS, TCA cycle, and fatty acid oxidation enzymes. Exercise also enhanced liver cholesterol and bile acid synthesis, reducing liver lipid metabolites in males after 8 weeks of exercise. Male rats had higher fecal cholesterol and cholic acid levels, indicating a sex-specific mechanism of lipid excretion with exercise. Moreover, 8 weeks of training reduced markers related to hepatic stellate cell activation and fibrosis in both sexes. This study highlights the sexual dimorphic and temporal molecular signatures by which exercise modulates liver metabolism to provide hepatoprotective effects.

  PublisherOA PDFDOI

• Metabolic Messengers: oestradiol

  Nature Metabolism · 2025-06-24 · 11 citations

  review1st authorCorresponding
  PublisherDOI

• A consensus guide to preclinical indirect calorimetry experiments

  Nature Metabolism · 2025-09-24 · 14 citations

  reviewOpen access
  PublisherOA PDFDOI

• Exercise training remodels inter-organ endocrine networks

  Molecular Metabolism · 2025-07-21 · 3 citations

  articleOpen access

  Exercise induces organism-wide molecular adaptations, partly mediated by humoral factors released in response to acute and chronic physical activity. However, the extent and specificity of endocrine effects from training-induced secreted factors remain unclear. Here, we applied systems genetics approaches to quantify inter-organ endocrine networks using multi-tissue transcriptomics and proteomics data collected from endurance-trained rats in The Molecular Transducers of Physical Activity Consortium (MoTrPAC). Eight weeks of endurance training significantly altered both the magnitude and specificity of endocrine effects across multiple origin-target tissue pairs. Subcutaneous white adipose tissue emerged as a key endocrine regulator impacted by training, while extracellular matrix-derived factors were identified as globally regulated secretory features in trained vs sedentary animals. Notably, secretory Wnt signaling factors were identified as key mediators of exercise-induced endocrine adaptations in multiple tissues. Our systems genetics framework provides an unprecedented atlas of inter-organ communication significantly remodeled by endurance exercise, serving as a valuable resource for novel exerkine discovery. • Exercise training remodels endocrine networks across 16 tissues, with subcutaneous white adipose tissue emerging as a key origin of secreted factors. • Systems genetics analysis using QENIE (Quantitative Endocrine Network Interaction Estimation) and GD-CAT (Gene-Derived Correlations Across Tissues) identifies secretory extracellular matrix proteins and Wnt signaling factors as central mediators of inter-organ communication induced by endurance training. • This study provides a multi-tissue atlas of exercise-induced endocrine interactions, serving as a resource for novel exerkine discovery and mechanistic investigation.

  PublisherDOI

• Workshop Report—Heterogeneity and Successful Aging Part I: Heterogeneity in Aging—Challenges and Opportunities

  The Journals of Gerontology Series A · 2025-03-07 · 2 citations

  article

  Historically, aging research has focused primarily on the study of differences in means of varied measures obtained at different ages. However, growing evidence has shown that for many parameters, variability in measurements obtained both between- and within-age groups increases with aging. Moreover, growing heterogeneity may become especially apparent when examined via longitudinal as opposed to cross-sectional aging data. Efforts to deconvolute and better understand such heterogeneity present remarkable translational opportunities for developing targeted and more effective interventions into aging. Here, we present Part I, a summary of the NIA Heterogeneity and Successful Aging workshop virtually held in May 2023.

  PublisherDOI

• Markers of mitochondrial function and oxidative metabolism in female skeletal muscle do not display intrinsic circadian regulation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-13 · 1 citations

  preprintOpen access

  Abstract Mitochondria are key regulators of metabolism and ATP supply in skeletal muscle, while circadian rhythms influence many physiological processes. However, whether mitochondrial function is intrinsically regulated in a circadian manner in mouse skeletal muscle is inadequately understood. Accordingly, we measured post-absorptive transcript abundance of markers of mitochondrial biogenesis, dynamics, and metabolism (extensor digitorum longus [EDL], soleus, gastrocnemius), protein abundance of electron transport chain complexes (EDL and soleus), enzymatic activity of SDH (tibialis anterior and plantaris), and maximum uncoupled respiration (tibialis anterior) in different skeletal muscles from female C57BL/6NJ mice at four zeitgeber times (ZT), ZT 1, 7, 13, and 19. Our findings demonstrate that markers of mitochondrial function and oxidative metabolism do not display intrinsic time-of-day regulation at the gene, protein, enzymatic, or functional level. The core-clock genes Bmal1 and Dbp exhibited intrinsic circadian rhythmicity in skeletal muscle (i.e., EDL, soleus, gastrocnemius) and circadian amplitude varied by muscle type. These findings demonstrate that female mouse skeletal muscle does not display circadian regulation of markers of mitochondrial function or oxidative metabolism over 24 hours.

  PublisherOA PDFDOI

Recent grants

• NIH Grant K01DK060484

  NIH · $542k · 2007

• Diabetes Research Center (DRC)

  NIH · $15.7M · 2002–2028

• NIH Grant R01DK109724

  NIH · $2.4M · 2022

• NIH Grant R21DK073227

  NIH · $419k · 2009

• The impact of HSP72 on mitochondrial function and muscle metabolism

  NIH · $2.1M · 2009–2029

Frequent coauthors

• Zhenqi Zhou

  University of California, Los Angeles

  44 shared

• Timothy M. Moore

  UCLA Health

  37 shared

• Marcus M. Seldin

  University of California, Irvine

  32 shared

• Jerrold M. Olefsky

  University of California, San Diego

  31 shared

• Brian G. Drew

  Baker Heart and Diabetes Institute

  27 shared

• Lauren M. Sparks

  Translational Research Institute for Metabolism and Diabetes

  26 shared

• Aldons J. Lusis

  University of California, Los Angeles

  26 shared

• Kenneth S. Korach

  National Institutes of Health

  22 shared

Education

• Ph.D., Molecular, Cellular, and Integrative Physiology

  University of California, Los Angeles

  2003

• M.S., Molecular, Cellular, and Integrative Physiology

  University of California, Los Angeles

  1998

• B.A., Biology

  University of California, Los Angeles

  1996

Awards & honors

• Sidney Roberts and Clara Szego Roberts Endowed Chair in Mole…