Synergistic Treatment of Obesity via Locally Promoting Beige Adipogenesis and Antioxidative Defense in Adipose Tissues

Abstract

Obesity is a primary risk factor for type 2 diabetes, cardiovascular diseases, cancer, and other chronic diseases. Current antiobesity medications need frequent administration and show limited efficacy with severe side effects. Herein, browning agent rosiglitazone (Rsg) and antioxidant manganese tetroxide nanoparticles (MnNPs, around 250 nm) are integrated into electrospun short fibers (SF@Rsg-Mn) with a 1.5 μm width and a 20 μm length. Upon injection into inguinal adipose tissues, SF@Rsg-Mn are well retained in the local depots to sustainably release Rsg in 30 days for adipose tissue browning, while MnNPs on the fiber surface continuously scavenge adipose reactive oxygen species (ROS) for an extended period of time. Synergistic inhibition of fat accumulation through ROS scavenging and white adipocyte browning has been demonstrated for the first time, and the optimal synergistic ratio of Rsg and MnNPs is determined to be 1/14 via combination index examination. SF@Rsg-Mn inhibit lipid accumulation through downregulation of adipogenic gene PPARγ while promoting energy expenditure through upregulation of brown-specific gene UCP1 and mitochondrial function gene COX7A1. In a diet-induced obesity mouse model, a single injection of SF@Rsg-Mn into inguinal adipose tissues has accomplished a synergistic effect on body weight loss, fat reduction, glucose, and lipid metabolic improvement while minimizing adverse effects on other tissues, thereby paving the way to efficacious, safe, and practical treatment of obesity.

Drinking Molecular Hydrogen Water Is Beneficial to Cardiovascular Function in Diet-Induced Obesity Mice

“…Emerging evidence proves that BAT activation or WAT browning in obesity is beneficial to cardiovascular health and decreases the risk of CVD [ 16 , 42 ].…”

Injectable cell-targeting fiber rods to promote lipolysis and regulate inflammation for obesity treatment

“…The antiobesity efficacy was examined in a DIO mouse model by assessing weight changes of mice, adipose tissue analysis, biochemical analysis of blood, and histological analysis of adipose tissues. 31 All animal procedures were performed in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals of China and approved by the Animal Care and Use Committee of Southwest Jiaotong University. Briefly, C57BL/6 mice (4 weeks old, 16 g) were supplied by Sichuan Dashuo Biotech.…”

“…30 Adipocytes were fixed with paraformaldehyde (4%) for 30 min, stained with Oil red O solution (0.6%) for 30 min, washed with isopropanol solution (60%) and then imaged by optical microscopy (Nikon TS100, Japan). 31 In addition, the stained cells were incubated with absolute isopropanol for 15 min to extract Oil red O, and the lipid level was detected by measuring the absorbance of Oil red O solution by UV-Vis spectrophotometry at 510 nm. 32 2.8 In vivo antiobesity efficacy of Ha R Chr and Ats F Rk treatment…”

Biomaterial-Based Therapeutic Strategies for Obesity and Its Comorbidities

“…In another study, the browning agent rosiglitazone and antioxidant manganese tetroxide nanoparticles (MnNPs) were integrated into poly(lactic acid)–poly(ethylene glycol) (PELA) electrospun fibers (SF@Rsg-Mn), which are 1.5 μm wide and 20 μm long [ 132 ]. After being injected into the inguinal adipose tissue of DIO mice, MnNPs at the surface of the fibers continuously scavenged adipose reactive oxygen species (ROS) and attenuated oxidative stress in adipose tissue, and rosiglitazone was continuously released for 30 days to induce adipose tissue browning for energy expenditure, thus synergistically alleviating obesity.…”