Daily Endocrinology Research Analysis
Top endocrinology advances today span microbiome–endocrine crosstalk in polycystic ovary syndrome, definitive evidence that SGLT2 inhibitors protect kidneys across KDIGO risk strata, and a cell-specific adiponectin–PPARγ axis that restrains liver fibrosis. Together, these studies open new therapeutic targets and refine guideline-relevant practice.
Summary
Top endocrinology advances today span microbiome–endocrine crosstalk in polycystic ovary syndrome, definitive evidence that SGLT2 inhibitors protect kidneys across KDIGO risk strata, and a cell-specific adiponectin–PPARγ axis that restrains liver fibrosis. Together, these studies open new therapeutic targets and refine guideline-relevant practice.
Research Themes
- Microbiome–endocrine–immune axis in metabolic diseases
- Kidney protection with SGLT2 inhibitors across risk spectrum
- Cell-specific drivers of fibrosis and metabolic cross-talk
Selected Articles
1. The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite.
Across three Chinese cohorts (n=226), the gut fungus Aspergillus tubingensis was enriched in PCOS and induced a PCOS-like phenotype upon colonization in mice by inhibiting AhR signaling and decreasing IL-22 in ILC3s. A strain-diversity metabolite screen identified AT-C1 as an endogenous AhR antagonist mediating the phenotype. This establishes a mycobiome-derived mechanism for PCOS and nominates AhR signaling restoration as a therapeutic strategy.
Impact: First mechanistic linkage of gut mycobiota and a defined fungal metabolite to PCOS via the AhR–ILC3–IL-22 axis opens a new pathogenic paradigm and drug target space.
Clinical Implications: Suggests screening the gut mycobiome in PCOS and exploring AhR pathway–modulating interventions (e.g., AhR agonists, microbiome/mycobiome modulation) as adjunctive therapies alongside lifestyle and ovulatory treatments.
Key Findings
- Aspergillus tubingensis was enriched in the gut of PCOS cohorts across three regions (total n=226).
- Colonization with A. tubingensis induced PCOS-like phenotypes in mice via inhibition of AhR signaling and reduced IL-22 from ILC3s.
- A strain-diversity-based metabolite screen identified AT-C1 as an endogenous AhR antagonist that mediated PCOS features.
Methodological Strengths
- Integration of human multi-cohort profiling with in vivo colonization models
- Mechanistic dissection of immune signaling (AhR/ILC3/IL-22) and metabolite-level causation
Limitations
- Human cohorts were restricted to three regions in China, potentially limiting generalizability.
- Causality in humans remains to be proven and metabolite exposure levels in human gut remain to be quantified.
Future Directions: Validate fungal prevalence and AT-C1 levels in diverse populations; test AhR-targeted or mycobiome-modulating therapies in PCOS; delineate dietary and environmental modifiers of the mycobiome–endocrine axis.
2. Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Outcomes across the Spectrum of Kidney Disease: A Systematic Review and Meta-Analysis.
In a meta-analysis of 10 large RCTs (n=78,184; median follow-up 2.7 years), SGLT2 inhibitors reduced composite kidney outcomes across KDIGO risk categories (HR range ~0.48–0.60) and UACR strata (HR ~0.61–0.80), without heterogeneity between groups. Benefits extended to lower-risk populations, though standardization of composites varied and non-diabetic representation was limited.
Impact: Consolidates the evidence base to support broader use of SGLT2 inhibitors for kidney protection beyond high-risk CKD, informing guidelines and payer decisions.
Clinical Implications: Supports prescribing SGLT2 inhibitors for kidney protection across KDIGO classes and albuminuria levels, with careful consideration of patient profiles and outcome definitions.
Key Findings
- Meta-analysis of 10 RCTs (n=78,184) showed SGLT2 inhibitors reduced composite kidney outcomes across KDIGO low to very high risk groups (HR ~0.48–0.60).
- Benefits were consistent across UACR categories (<30, 30–300, >300 mg/g) with HRs ~0.61–0.80 and no heterogeneity between groups.
- Risk of bias was low; GRADE applied; registration CRD42023492877. Limitations include limited representation of non-diabetic low-risk populations and varying composite definitions.
Methodological Strengths
- Large-scale synthesis of randomized placebo-controlled trials with low risk of bias
- Stratified analyses across KDIGO and UACR with random-effects modeling and GRADE assessment
Limitations
- Composite kidney outcomes were not standardized across trials.
- Lower representation of non-diabetic low-risk participants limits generalization to that subgroup.
Future Directions: Harmonize outcome definitions and expand trials in non-diabetic, lower-risk cohorts; assess cost-effectiveness and implementation in diverse healthcare systems.
3. The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis.
Using an HSC-specific inducible transgenic system (Lrat-rtTA), the authors show that HSC ablation protects against MCD diet-induced fibrosis and that HSC-specific adiponectin overexpression suppresses, while deletion accelerates, fibrosis. They define a local adiponectin–PPARγ axis in HSCs that regulates fibrosis independently of circulating adiponectin.
Impact: Reveals a cell-intrinsic adiponectin–PPARγ brake on fibrosis, shifting focus from systemic to local adipokine signaling and providing a precise antifibrotic target.
Clinical Implications: Suggests potential for HSC-targeted PPARγ activation or enhancement of local adiponectin signaling in liver fibrosis, complementing systemic metabolic therapies for NASH/NAFLD.
Key Findings
- An HSC-specific, doxycycline-inducible Lrat-rtTA line enables precise gene manipulation in stellate cells.
- HSC ablation protects against MCD diet-induced fibrosis, confirming causal involvement of HSCs.
- HSC-specific adiponectin overexpression reduces, while deletion accelerates, fibrosis via a local adiponectin–PPARγ axis independent of circulating adiponectin.
Methodological Strengths
- Cell-type–specific inducible genetic models enabling causal inference
- Concordant gain- and loss-of-function studies across in vivo fibrosis models
Limitations
- Primarily MCD diet model; validation in additional fibrosis etiologies (e.g., toxic, cholestatic) is needed.
- Translational biomarkers linking HSC-local signaling to human fibrosis progression remain to be established.
Future Directions: Test HSC-targeted PPARγ modulators and enhance local adiponectin signaling in diverse fibrosis models; develop imaging/serologic biomarkers of HSC PPARγ activity for clinical translation.