As an escalating public health issue, obesity and overweight
conditions
are predispositions to various diseases and are exacerbated by concurrent
chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals
(quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy
alongside systemic toxic effects. Effective therapeutic approaches
that selectively target adipose tissue, thereby enhancing local energy
expenditure, surmounting the limitations of prevailing antiobesity
modalities are highly expected. In this context, we developed a temperature-sensitive
hydrogel loaded with recombinant high-density lipoprotein (rHDL) to
achieve targeted delivery of resveratrol, an adipose browning activator,
to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism
and demonstrates natural targeting toward scavenger receptor class
B type I (SR-BI), which is highly expressed by fat cells, thereby
achieving a synergistic effect for the treatment of obesity. Additionally,
the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled
with the regulation of their degradation and drug release rate, facilitated
sustainable drug release at local adipose tissues over an extended
period. Following 24 days' treatment regimen, obese mice exhibited
improved metabolic status, resulting in a reduction of 68.2% of their
inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel
facilitated the conversion of fatty acids to phospholipids (PA, PC),
expediting fat mobilization, mitigating triglyceride accumulation,
and therefore facilitating adipose tissue reduction. Furthermore,
rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced
inflammation and fostering angiogenesis in ingWAT. Collectively, this
engineered local fat reduction platform demonstrated heightened effectiveness
and safety through simultaneously targeting adipocytes, promoting
WAT browning, regulating lipid metabolism, and controlling inflammation,
showing promise for adipose-targeted therapy.