Weekly Endocrinology Research Analysis
This week’s endocrinology literature emphasized translational mechanisms that reshape metabolic control and rapid clinical studies with immediate practice implications. Top mechanistic reports identified a feeding-induced myokine (feimin–MERTK) regulating glucose and a chaperone-driven TOM70 insertion pathway that enhances thermogenesis and protects against diet-induced obesity. A randomized phase 2 trial repurposed empagliflozin to lower urinary stone supersaturation in nondiabetic stone former
Summary
This week’s endocrinology literature emphasized translational mechanisms that reshape metabolic control and rapid clinical studies with immediate practice implications. Top mechanistic reports identified a feeding-induced myokine (feimin–MERTK) regulating glucose and a chaperone-driven TOM70 insertion pathway that enhances thermogenesis and protects against diet-induced obesity. A randomized phase 2 trial repurposed empagliflozin to lower urinary stone supersaturation in nondiabetic stone formers, suggesting near-term prevention trials.
Selected Articles
1. A feeding-induced myokine modulates glucose homeostasis.
This study identifies feimin, a muscle-derived myokine secreted during feeding, which binds MERTK to activate AKT, increasing glucose uptake and suppressing hepatic glucose production. In mice feimin synergizes with insulin to improve glycaemia, and a human MERTK variant (R466K) reduces feimin binding and associates with higher postprandial glucose and insulin.
Impact: Reveals a previously unknown endocrine muscle–liver axis with translational hooks (human genetics and pharmacologic synergy) that could be targeted to improve postprandial glucose control.
Clinical Implications: Feimin–MERTK signaling is a candidate therapeutic target or biomarker to augment postprandial glycemic control; MERTK variants may stratify patients for tailored interventions pending human validation.
Key Findings
- Feimin is secreted from skeletal muscle during feeding and binds MERTK.
- Feimin–MERTK activates AKT to increase glucose uptake and suppress hepatic glucose production.
- Feimin plus insulin synergistically improves glycaemia in mice.
- Human MERTK R466K variant reduces feimin binding and associates with higher postprandial glucose/insulin.
2. Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity.
The stress-induced chaperone PPID promotes insertion of TOM70 into the outer mitochondrial membrane, enhancing brown adipocyte respiration and thermogenesis. In obese mice this PPID–TOM70 pathway preserves body temperature regulation and limits weight gain, revealing a novel proteostasis node that controls energy expenditure.
Impact: Uncovers a novel chaperone-dependent control of mitochondrial protein insertion directly linked to thermogenesis and obesity risk, opening new anti-obesity target space outside classical hormonal pathways.
Clinical Implications: Preclinical target that could be pursued to boost adaptive thermogenesis in obesity/metabolic syndrome after human validation of safety and targetability of PPID–TOM70 modulation.
Key Findings
- PPID drives TOM70 insertion into the outer mitochondrial membrane via PPIase and TPR domains.
- TOM70 insertion enhances brown adipocyte respiratory and thermogenic function.
- PPID–TOM70 activity modulates body temperature and weight in obese mice under cold/high-calorie stress.
3. Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial.
In a double-blind, placebo-controlled crossover Phase 2 trial (n=53), empagliflozin 25 mg reduced urinary relative supersaturation for calcium phosphate by ~36% in calcium stone formers and for uric acid by ~30% in uric acid stone formers, with no serious adverse events during short treatment periods—supporting further prevention trials in nondiabetic stone disease.
Impact: High-quality RCT evidence supporting repurposing an SGLT2 inhibitor to alter validated urinary surrogates of stone risk in nondiabetic patients—immediately actionable for designing definitive recurrence trials.
Clinical Implications: Empagliflozin is a promising candidate for stone prevention in nondiabetic calcium-phosphate and uric acid stone formers; longer, multicenter trials powered for clinical recurrence and long-term safety are the next step before routine clinical adoption.
Key Findings
- Empagliflozin reduced calcium phosphate relative supersaturation by ~36% in calcium stone formers.
- Empagliflozin reduced uric acid relative supersaturation by ~30% in uric acid stone formers.
- No serious or prespecified adverse events occurred during the short crossover treatment periods.