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Loss of CTRP10 results in female obesity with preserved metabolic health.
Authors Chen F, Sarver DC, Saqib M, Velez LM, Aja S, Seldin MM, Wong GW
Submitted By Submitted Externally on 3/15/2024
Status Published
Journal bioRxiv : the preprint server for biology
Year 2023
Date Published 11/1/2023
Volume : Pages Not Specified : Not Specified
PubMed Reference 37961647
Abstract Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular
disease, and hypertension. Intriguingly, there is a subset of metabolically
healthy obese (MHO) individuals who are seemingly able to maintain a healthy
metabolic profile free of metabolic syndrome. The molecular underpinnings of
MHO, however, are not well understood. Here, we report that
CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10
modulates weight gain in a striking and sexually dimorphic manner. Female, but
not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while
maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet,
female Ctrp10 knockout (KO) mice show rapid weight gain. Despite pronounced
obesity, Ctrp10 KO female mice do not develop steatosis, dyslipidemia, glucose
intolerance, insulin resistance, oxidative stress, or low-grade inflammation.
Obesity is largely uncoupled from metabolic dysregulation in female KO mice.
Multi-tissue transcriptomic analyses highlighted gene expression changes and
pathways associated with insulin-sensitive obesity. Transcriptional correlation
of the differentially expressed gene (DEG) orthologous in humans also show sex
differences in gene connectivity within and across metabolic tissues,
underscoring the conserved sex-dependent function of CTRP10. Collectively, our
findings suggest that CTRP10 negatively regulates body weight in females, and
that loss of CTRP10 results in benign obesity with largely preserved insulin
sensitivity and metabolic health. This female MHO mouse model is valuable for
understanding sex-biased mechanisms that uncouple obesity from metabolic


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