Weekly Endocrinology Research Analysis
This week’s endocrinology literature highlights mechanistic and translational advances linking microbiome and redox biology to systemic endocrine disease, along with pragmatic clinical studies that refine therapeutics and monitoring. A mechanistic mycobiome–AhR axis was implicated in PCOS, while pentose phosphate pathway and PRDX1 redox regulation revealed new targets for cartilage and liver disease respectively. Large trials and meta-analyses clarified clinical practice: time-restricted eating
Summary
This week’s endocrinology literature highlights mechanistic and translational advances linking microbiome and redox biology to systemic endocrine disease, along with pragmatic clinical studies that refine therapeutics and monitoring. A mechanistic mycobiome–AhR axis was implicated in PCOS, while pentose phosphate pathway and PRDX1 redox regulation revealed new targets for cartilage and liver disease respectively. Large trials and meta-analyses clarified clinical practice: time-restricted eating added no visceral-fat benefit beyond Mediterranean diet, SGLT2 inhibitors show consistent kidney protection across risk strata, and CGM improves inpatient glycemic time-in-range.
Selected Articles
1. The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite.
Human multi-cohort profiling found enrichment of the gut fungus Aspergillus tubingensis in PCOS; mouse colonization reproduced PCOS-like features via AhR inhibition and reduced ILC3-derived IL-22. A strain-based metabolite screen identified AT-C1, an endogenous AhR antagonist, as a causal mediator, linking a defined fungal metabolite to endocrine dysfunction.
Impact: Provides the first mechanistic link between a gut mycobiome member and PCOS through a defined fungal metabolite and immune axis (AhR–ILC3–IL-22), opening a novel pathogenic paradigm and targetable pathway.
Clinical Implications: Suggests screening and modulation of the gut mycobiome (or targeting AhR signaling) as potential adjunct strategies for PCOS management; requires validation in diverse human populations and interventional trials.
Key Findings
- Enrichment of Aspergillus tubingensis in gut samples from PCOS cohorts across three regions in China (total n=226).
- Mouse colonization with A. tubingensis induced PCOS-like features by inhibiting AhR signaling and lowering ILC3-derived IL-22.
- AT-C1, a strain-diversity–derived metabolite, functions as an endogenous AhR antagonist mediating the phenotype.
2. The pentose phosphate pathway controls oxidative protein folding and prevents ferroptosis in chondrocytes.
Chondrocyte-specific loss of G6PD demonstrated that PPP-derived NADPH is essential to maintain glutathione recycling, protect against ROS generated during oxidative protein folding, prevent unfolded protein response activation, and avert ferroptosis—culminating in chondrodysplasia. The study establishes PPP as a redox gatekeeper for proteostasis in hypoxic cartilage, with implications for skeletal repair.
Impact: Defines a fundamental metabolic mechanism coupling oxidative protein folding to ferroptosis and skeletal phenotype, nominating PPP/NADPH and ferroptosis pathways as potential therapeutic nodes for cartilage disorders and fracture repair.
Clinical Implications: Supports exploration of strategies to boost PPP flux or NADPH availability, or to inhibit ferroptosis, as approaches to enhance cartilage resilience in growth disorders and repair—pending translational validation.
Key Findings
- G6PD loss in chondrocytes reduces NADPH, impairs glutathione recycling, and compromises protection against ROS from oxidative protein folding.
- Proteostasis disruption activates the unfolded protein response and increases protein degradation.
- Oxidative stress-induced ferroptosis and matrix changes lead to chondrodysplasia, establishing PPP as essential for endochondral ossification.
3. Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.
This study shows palmitic acid binds PRDX1 and inhibits its peroxidase activity, reducing hepatic H2O2 scavenging and promoting STAT signaling, PTP oxidation, lipid peroxidation, and NASH progression in male mice. Using structural biology, rosmarinic acid was identified as a PRDX1 agonist that stabilizes the peroxidatic cysteine and ameliorates disease, nominating PRDX1 activation as a druggable NASH strategy.
Impact: Identifies a direct, druggable mechanistic link between saturated fatty acids and oxidative stress in NASH, and provides structural validation of a small-molecule PRDX1 agonist—bridging mechanism to potential therapeutics.
Clinical Implications: While preclinical, findings justify development of selective PRDX1 activators and assessment of redox-targeted approaches in NASH clinical programs; translational work should address sex differences, PK/PD, and safety.
Key Findings
- Palmitic acid binds PRDX1 and inhibits its peroxidase activity, contributing to reduced hepatic ROS scavenging in NASH models.
- Hepatic PRDX1 protects against NASH via H2O2 scavenging, suppression of STAT signaling, and prevention of PTP oxidation and lipid peroxidation.
- Rosmarinic acid binds PRDX1 (crystal structure), stabilizes the peroxidatic cysteine, activates peroxidase activity, and alleviates NASH in mice.