Endocrinology Research Analysis
Endocrinology in January 2025 was defined by inter-organ endocrine circuits and pragmatic, implementation-ready trials. Science reports uncovered a muscle–pituitary myostatin axis driving FSH and a fasting-activated intestinal neuron→ILC2→pancreas circuit regulating glucagon, reframing systemic endocrine control. Translational advances included a multicenter RCT showing dapagliflozin added to structured calorie restriction substantially increases type 2 diabetes remission, and a Nature Communica
Summary
Endocrinology in January 2025 was defined by inter-organ endocrine circuits and pragmatic, implementation-ready trials. Science reports uncovered a muscle–pituitary myostatin axis driving FSH and a fasting-activated intestinal neuron→ILC2→pancreas circuit regulating glucagon, reframing systemic endocrine control. Translational advances included a multicenter RCT showing dapagliflozin added to structured calorie restriction substantially increases type 2 diabetes remission, and a Nature Communications study revealing a liver→brain vagal sensory pathway linking steatosis, energy balance, and anxiety-like behavior. Microbiome–endocrine crosstalk emerged with a mycobiome-derived AhR antagonist implicated in PCOS. Normalized and recency-weighted scoring prioritized late-month clinical and mechanistic papers with near-term practice implications.
Selected Articles
1. APOBEC-1 cofactors regulate APOBEC3-induced mutations in hepatitis B virus.
HBV replication models show APOBEC-1 cofactors and hnRNPs physically associate with APOBEC3 proteins to enhance mutational activity; disrupting these interactions reduces APOBEC3 mutagenesis, while APOBEC-1 cofactors increase A3C access to HBV (−)DNA driving kataegis-like hypermutation.
Impact: Identifies host interaction nodes controlling APOBEC3 mutagenesis at the intersection of antiviral defense and cancer mutagenesis, nominating modifiable cofactors and hnRNPs as therapeutic or biomarker targets.
Clinical Implications: Targeting APOBEC-1 cofactor/hnRNP interactions could limit APOBEC-driven tumor mutagenesis or augment antiviral restriction; supports development of biomarkers for A3 activity in HBV and potentially cancers.
Key Findings
- APOBEC-1 cofactors and hnRNPs strongly interact with APOBEC3 proteins and enhance mutational activity.
- Disruption of A3–hnRNP interactions markedly reduces APOBEC3-driven mutagenesis.
- A1 cofactors increase A3C accessibility to HBV (−)DNA, promoting kataegis-like hypermutation.
2. Dapagliflozin plus calorie restriction for remission of type 2 diabetes: multicentre, double blind, randomised, placebo controlled trial.
A multicenter, double-blind RCT (n=328) showed dapagliflozin 10 mg/day plus structured calorie restriction achieved 44% diabetes remission at 12 months vs 28% with diet plus placebo (RR 1.56), with greater improvements in weight, HOMA-IR, body fat, and systolic blood pressure and no increase in adverse events.
Impact: Provides high-quality randomized evidence that pharmacologic augmentation with SGLT2 inhibitors materially increases diet-driven remission—informing remission-oriented pathways and guidelines.
Clinical Implications: For overweight/obese early T2D patients pursuing remission, consider dapagliflozin alongside structured calorie restriction with individualized monitoring of renal function, volume status, and durability of remission.
Key Findings
- 12-month remission improved to 44% with dapagliflozin + diet vs 28% with diet + placebo (RR 1.56).
- Greater reductions in body weight, HOMA-IR, body fat, and systolic blood pressure with dapagliflozin.
- No significant difference in adverse events over 12 months.
3. Liver-innervating vagal sensory neurons are indispensable for the development of hepatic steatosis and anxiety-like behavior in diet-induced obese mice.
Selective ablation of liver-projecting vagal sensory neurons increased energy expenditure, prevented diet-induced obesity, attenuated hepatic steatosis, improved glucose homeostasis (with male-specific insulin sensitivity gains), and reduced anxiety-like behavior—defining a causal liver→brain neural pathway.
Impact: Reveals a discrete, targetable organ→brain circuit linking steatosis, energy balance, and behavior, opening neuromodulation strategies for MAFLD/obesity with neuropsychiatric comorbidity.
Clinical Implications: Motivates translational development of neuromodulatory therapies (afferent modulation/devices) and biomarkers to quantify liver→brain signaling in human obesity and MAFLD.
Key Findings
- Ablation of liver-projecting vagal sensory neurons prevents diet-induced obesity by increasing energy expenditure.
- Loss of these neurons limits hepatic steatosis and improves glucose homeostasis; males show increased insulin sensitivity.
- Neuronal loss reduces anxiety-like behavior, implicating the liver–brain axis in behavioral regulation.
4. Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis.
Mouse studies demonstrate myostatin acts systemically as an endocrine hormone to directly stimulate pituitary FSH synthesis, establishing a skeletal muscle–pituitary axis and challenging activin’s primacy in FSH regulation.
Impact: Redefines reproductive hormonal hierarchies and raises immediate safety/efficacy considerations for myostatin-targeting therapeutics.
Clinical Implications: Myostatin antagonism (in development for muscle disorders) may affect fertility; monitoring and counseling should be considered.
Key Findings
- Myostatin directly promotes pituitary FSH synthesis in vivo.
- Establishes a skeletal muscle–pituitary endocrine axis challenging activin primacy.
- Therapeutic myostatin antagonism may have unintended fertility effects.
5. The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite.
Human multi-cohort profiling found enrichment of Aspergillus tubingensis in PCOS; mouse colonization reproduced PCOS-like features via AhR inhibition and reduced ILC3-derived IL-22. A metabolite, AT-C1, functions as an endogenous AhR antagonist mediating the phenotype.
Impact: Establishes a causal mycobiome–immune–endocrine axis in PCOS with a defined fungal metabolite, opening AhR-targeted therapeutic strategies.
Clinical Implications: Suggests screening/modulating the gut mycobiome or targeting AhR signaling as adjunct strategies for PCOS; requires validation in diverse populations and interventional trials.
Key Findings
- A. tubingensis enrichment observed across human PCOS cohorts.
- Mouse colonization induces PCOS-like features via AhR inhibition and reduced IL-22 from ILC3s.
- AT-C1 identified as an endogenous AhR antagonist mediating the phenotype.