Microneedles-based local photothermal therapy promotes browning of white adipose tissue and combats obesity

Fig. 1. Schematic illustration of Fe3O4@MNP based LPTT to promote WAT browning in HFD-induced obesity.

Fig. 2. Characterization of Fe3O4@MNP. a) Digital image of Fe3O4@MNP. b) Optical image of Fe3O4@MNP. c) SEM image of Fe3O4@MNP. d) Elemental analysis of the selected area in the tip of Fe3O4@MNP. e) Force-displacement curve of MNP and Fe3O4@MNP. f) H&E staining image of porcine skin after puncture by Fe3O4@MNP loaded with trypan blue. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3. Photothermal property of Fe3O4@MNP. a) Temperature curves of Fe3O4@MNP under NIR irradiation with different powers. b) Infrared thermal images of MNP and Fe3O4@MNP under NIR irradiation (1.25 W/cm2). c) Temperature curve of Fe3O4@MNP under NIR irradiation with three laser on/off cycles (1.25 W/cm2). d) Infrared thermal images of inguinal skin area in mice with different treatments (1.25 W/cm2, 2 min), and the maximal temperature on the inguinal skin area (n = 4).

Fig. 4. The anti-obesity efficacy of Fe3O4@MNP-based LPTT in HFD-induced obese mice. a) Schematic illustration of the treatment procedure. b) Body weight change curve of mice during treatment (n = 6). c) Images of mice after treatment. d, e) Images and weights of BAT and WAT (n = 6). f) H&E staining images of BAT and WAT. Scale bar: 50 μm. g) Morphometric analysis of adipocyte size in WAT. h) GTT results and AUC (n = 5). i) Serum glucose level (n = 3).

Fig. 5. The therapeutic efficacy of Fe3O4@MNP-based LPTT in lipid metabolism disorder and NAFLD in HFD-induced obese mice. a) Levels of TG, TC, LDL-C, and HDL-C in serum (n = 3). b) H&E and Oil Red O staining images of liver. Scale bar: 100 μm. c) Liver weight (n = 6). d) Levels of TG and TC in liver (n = 3). e) Levels of ALT and AST in serum (n = 3). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 6. The effect of Fe3O4@MNP-based LPTT on WAT browning in HFD-induced obese mice. a) mRNA expressions of Ucp1, Cidea, and Sirt1 in iWAT (n = 3). b) Western blotting for UCP1 protein in iWAT and relative quantitative analysis (n = 3). c) Immunofluorescence images of UCP1 protein in iWAT (green fluorescence: UCP1; blue fluorescence: nuclei). Scale bar: 100 μm. d) mRNA expressions of Hsf1 and Pgc1a in iWAT (n = 3). e) Western blotting for HSF1, PGC1α and HSP72 protein expressed in iWAT and relative quantitative analysis (n = 3). f) Immunofluorescence images of HSF1 and PGC1α protein in iWAT (green fluorescence: PGC1α; red fluorescence: HSF1; blue fluorescence: nuclei). Scale bar: 100 μm. g) Schematic illustration of LPTT promoting WAT browning and thermogenesis through the activation of HSF1-PGC1α transcriptional axis. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)