Gene therapy approaches for obesity-induced adipose neuropathy: Device-targeted AAV-mediated neurotrophic factor delivery to adipocytes in subcutaneous adipose.

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

SUBMITTER: Blaszkiewicz M 

PROVIDER: S-EPMC11081869 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature