NPY₁R-targeted peptide-mediated delivery of a dual PPARα/γ agonist to adipocytes enhances adipogenesis and prevents diabetes progression.

ABSTRACT:

Objective

PPARα/γ dual agonists have been in clinical development for the treatment of metabolic diseases including type 2 diabetes and dyslipidemia. However, severe adverse side effects led to complications in clinical trials. As most of the beneficial effects rely on the compound activity in adipocytes, the selective targeting of this cell type is a cutting-edge strategy to develop safe anti-diabetic drugs. The goal of this study was to strengthen the adipocyte-specific uptake of the PPARα/γ agonist tesaglitazar via NPY₁R-mediated internalization.

Methods

NPY₁R-preferring peptide tesaglitazar-[F⁷, P³⁴]-NPY (tesa-NPY) was synthesized by a combination of automated SPPS and manual couplings. Following molecular and functional analys

SUBMITTER: Wittrisch S 

PROVIDER: S-EPMC6931124 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature