ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Gene therapy approaches for obesity-induced adipose neuropathy: Device-targeted AAV-mediated neurotrophic factor delivery to adipocytes in subcutaneous adipose.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 9 citations in OpenAlex.
- A non-invasive method for light-inducible knockout across all cell types in mouse subcutaneous adipose tissue.Adipocyte · 2026Article
- Targeting the peripheral nervous system in adipose tissue with engineered AAV vectors.Cell reports methods · 2026Article
- The Adipose-Sympathetic Nerve Crosstalk: FSTL1 as an Adipocyte-Derived Neurotrophic Factor for WAT Browning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bone Morphogenetic Proteins in Obesity Management: Therapeutic Potential and Challenges Beyond the Skeleton.Current medical science · 2026Review
- Mechanisms, translational opportunities for diabetic polyneuropathy.Frontiers in endocrinology · 2026Review
- Diabetic Peripheral Neuropathy: New Diagnostics and Treatment Perspectives.Drugs & aging · 2026Review
- DNA-mediated UCP1 overexpression in adipose tissue: A promising anti-obesity gene therapy.Clinical and translational medicine · 2025Article
- Dose-finding andMolecular therapy. Methods & clinical development · 2025Article
- Serpina3c deficiency promotes obesity-related hypertriglyceridemia and inflammation through activation of the Hif1α-glycolysis axis in adipose tissue.Clinical science (London, England : 1979) · 2025Article
- Review
- Transdermal electrophysiological recordings of diet-induced small fiber peripheral neuropathy using a needle electrode array in mice and man.Frontiers in bioengineering and biotechnology · 2024Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Maintaining functional adipose innervation is critical for metabolic health. We found that subcutaneous white adipose tissue (scWAT) undergoes peripheral neuropathy (PN) with obesity, diabetes, and aging (reduced small-fiber innervation and nerve/synaptic/growth-cone/vesicle markers, altered nerve activity). Unlike with nerve injuries, peripheral nerves do not regenerate with PN, and therefore new therapies are needed for treatment of this condition affecting 20-30 million Americans. Here, we validated a gene therapy approach using an adipocyte-tropic adeno-associated virus (AAV; serotype Rec2) to deliver neurotrophic factors (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) directly to scWAT to improve tissue-specific PN as a proof-of-concept approach. AAVRec2-BDNF intra-adipose delivery improved tissue innervation in obese/diabetic mice with PN, but after longer periods of dietary obesity there was reduced efficacy, revealing a key time window for therapies. AAVRec2-NGF also increased scWAT innervation in obese mice and was more effective than BDNF, likely because Rec2 targeted adipocytes, the tissue's endogenous NGF source. AAVRec2-NGF also worked well even after 25 weeks of dietary obesity, unlike BDNF, which likely needs a vector that targets its physiological cellular source (stromal vascular fraction cells). Given the differing effects of AAVs carrying NGF versus BDNF, a combined therapy may be ideal for PN.
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