Journal article
Sexual dimorphism shapes renal metabolic adaptation to a ketogenic diet
Cell reports (Cambridge), Vol.45(4), pp.117190-117190
04/28/2026
DOI: 10.1016/j.celrep.2026.117190
PMID: 41904948
Abstract
While kidneys are essential for maintaining systemic metabolic homeostasis and exhibit sexual dimorphism, the effects of sex and environmental factors, such as diet, on renal metabolism remain unclear. Using kidney-specific arteriovenous (AV) metabolomics, in vivo isotope tracing, and transcriptomics, we discover profound sex differences in kidney metabolic reprogramming under ketogenic diet (KD) in C57BL/6J mice. Tissue metabolomics shows the accumulation of aldosterone and acylcarnitines exclusively in female kidneys under a normal chow (NC) diet, suggesting basal sex differences in sodium and fatty acid metabolism. Under KD, AV metabolomics reveals that only female kidneys activate ketogenesis and gluconeogenesis, supported by transcriptional sex differences in related rate-limiting enzymes and transporters. Given the widespread public and clinical interest in KD for treating epilepsy, metabolic disorders, and cancers, our findings underscore the importance of considering sex differences in kidney metabolism as a fundamental variable when interpreting KD’s diverse effects on pathophysiology and therapeutics.
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•Kidney metabolomics reveals female-specific aldosterone accumulation•Arteriovenous metabolomics reveals sex differences in kidney metabolic activities•Ketogenic diet induces female-specific renal gluconeogenesis and ketogenesis•Induction of key rate-limiting enzymes mediates gluconeogenesis and ketogenesis
By tracking metabolites entering and leaving the kidney in mice, Kelly et al. uncovered strong sex differences in kidney metabolism under normal and ketogenic diets. Female kidneys showed unexpected increases in sugar and ketone production on a ketogenic diet, highlighting sex as an important factor in kidney health and disease.
Details
- Title: Subtitle
- Sexual dimorphism shapes renal metabolic adaptation to a ketogenic diet
- Creators
- Miranda E. Kelly - University of California, IrvineLauren A. Hoffner - University of California, IrvineCuauhtemoc B. Ramirez - University of California, IrvineAlexis L. Anica - University of California, IrvineJoohwan Kim - University of California, IrvineGregory Tong - University of California, IrvineYeojin Kim - University of California, IrvineVyshnavi Mannepalli - University of California, IrvineWonsuk Choi - University of California, IrvineKi-Hong Jang - University of California, IrvineYasmine H. Alam - University of California, IrvineSunhee Jung - University of California, IrvineJohnny Le - University of California, IrvineMiranda L. Lopez - University of California, IrvineVarvara I. Rubtsova - University of California, IrvineHosung Bae - University of California, IrvineYujin Chun - University of California, IrvineWon-Suk Song - University of California, IrvineIan J Tamburini - University of California, IrvineVictor L. Schuster - Albert Einstein College of MedicineHoda Anton-Culver - University of California, IrvineWei Ling Lau - University of California, IrvineThomas F. Martinez - University of California, IrvineGina Lee - University of California, IrvineCholsoon Jang - University of California, Irvine
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.45(4), pp.117190-117190
- DOI
- 10.1016/j.celrep.2026.117190
- PMID
- 41904948
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 04/28/2026
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985217030702771
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