Lignin-Assisted local release of triiodothyronine in adipose tissue protects mice against obesity and related metabolic disorders

Lignin is considered a promising carrier for drugs with aromatic structures via co-self-assembly, endowing the composite particles with functional properties for biomedical applications. Triiodothyronine (T3) has exhibited beneficial effects in obesity and obesity-related metabolic disorders by increasing the energy expenditure of adipose tissue; however, excess thyroid hormones may adversely affect various tissues. T3, which contains benzene rings and hydrophilic functional groups, is co-self-assembled with lignin to fabricate composite lignin–triiodothyronine (L-T3) particles using solvent-shifting methods. The dual driving forces of hydrogen bonding and π–π interactions enhance the co-self-assembly tendency of lignin and T3, thereby improving their distributions in the composite particles. L-T3 can be taken up by adipocytes with well controlled particle size. Moreover, a single locally delivered L-T3 dose to the subcutaneous white adipose tissue (sWAT) of mice does not affect mouse plasma T3 levels, but decreases the adipocyte size and increases uncoupling protein (UCP-1) expression in the sWAT of normal diet and short-term high-fat diet (HFD)-fed mice. Notably, L-T3 decreases body and adipose tissue weights in long-term HFD-fed mice. Furthermore, HFD-induced liver steatosis is substantially ameliorated by local delivery of L-T3 to sWAT. These results suggest that local delivery of L-T3 in adipose tissue exhibits protective effects against obesity and related metabolic disorders.