(PO25-01-22) Browning Subcutaneous White Adipose Tissue Using Transdermal Delivery of ASC-Targeting Peptide and Resveratrol Conjugate

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Presenting Author(s)

Mehrnaz Abbasi, PhD Nutritional Sciences
– Postdoctoral Scholar, Arizona State University, Phoenix, Arizona, United States

Co-Author(s)

SW

Shu Wang, MD, PhD Nutritional Biochemistry and Metabolism
– Faculty, Arizona State University, Phoenix, Arizona, United States

Disclosure(s):

Mehrnaz Abbasi, PhD Nutritional Sciences: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Trans-resveratrol (RES) can significantly enhance the browning of subcutaneous white adipose tissue (WAT) when delivered to adipose stromal stem cells (ASCs) in WAT, the precursors of beige adipocytes. ASC-targeting peptide (GSWKYWFGEGGC) and RES have been conjugated using succinyl as a linker. The objective of this study is to transdermally deliver ASC-targeting peptide-RES conjugate directly to subcutaneous WAT using microneedle (MN) and iontophoresis (INT) and validate their browning and anti-obesity efficacy in obese mice.

Methods: Dissolving MN patches were developed using carboxymethylcellulose (CMC). Delivery effectiveness of MN was determined by an in vivo fluorescence imaging after applying dye-loaded MN on the skin above inguinal WAT (iWAT) in mice. Peptide-RES conjugate was loaded into CMC MN that was applied on the skins above iWAT of mice. After MN were dissolved, INT patch was applied to enhance penetration. Male C57BL/6J mice (5/group) were fed ahigh fat diet for 9 weeks. After 4 weeks of the high fat diet, mice were randomly divided into 3 groups as 1. MN (Blank)+INT, 2. MN (free RES)+INT, and 3. MN (peptide-RES conjugate) +INT. Mice received treatments 2 times/week from week 5 to 9. Food intake, body weight, and body composition were measured weekly, and the glucose tolerance test was conducted at week 9.

Results: MN (dye)+INT-treated mice had 2-fold higher dye signals in iWAT as compared to mice treated with MN alone. Dye signals in other organs/tissues were too low to be detected indicating the success of local (MN+INT) delivery and less diffusion. After 5 weeks of treatment, mice treated with MN (peptide-RES conjugate)+INT as compared to other two groups of mice had more than 1.5-fold lower body weight and fat%, 1.4-fold lower blood glucose levels, and more than 3-fold iWAT mRNA levels of UCP1 indicating browning of iWAT.

Conclusions: Transdermal delivery of ASC-targeting peptide-RES conjugate to iWAT induces browning of subcutaneous WAT, resulting in body weight and fat loss in obese mice. Transdermal delivery might provide an innovative and efficient approach for combating obesity and its comorbidities.

Funding Sources: NIH 1R15AT010395-01 and American Heart Association 19AIREA34480011