Poly-L-Lactic Acid Reduces the Volume of Dermal Adipose Tissue Through its Metabolite Lactate

Poly-L-lactic acid (PLLA), a well-established biostimulator that induces collagenases, is widely used among clinical practice to treat skin aging. However, the precise regulatory effect of PLLA on different dermal cell subsets beyond fibroblast has not been fully elucidated. In this study, we constructed in vivo PLLA injection and in vitro PLLA-adipocyte co-culture models to analyze the regulatory effects of PLLA on the volume, differentiation, lipolysis, and thermogenic capacity of dermal adipocyte. We found that PLLA injection significantly reduced the thickness of dermal fat in mice. In co-culture assay, PLLA showed no effect on adipogenesis, but stimulated the lipolysis activity. Interestingly, PLLA also enhanced the differentiation of fat cells into beige fat cells, which possess higher thermogenic capacity. In mechanical study, we blocked adipocyte lactate uptake with a monocarboxylate transporter (MCT1/4) inhibitor and found that the regulatory effect of PLLA on dermal adipocyte relies on its metabolite lactate. In summary, our results suggest that PLLA has complex regulatory effects on the dermal cells, and its ability to improve skin aging is not fully attributed to stimulating collagen synthesis, but also partially involves adipocytes.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .