Table 2.
Studies establishing adipose organoids as drug screening platforms for obesity-related metabolic diseases
| Diseases | Studies | Sources | Methods | Efficiency validation | Screening drugs | Highlight results | In vivo validation |
|---|---|---|---|---|---|---|---|
| Obesity | Choi et al. (2022)122 | mice 3T3-L1 preadipocytes and macrophages (RAW264.7) |
-Suspended in alginate hydrogel mixture for bioprinting of 3D beads; -Tested in 96-well platforms |
-Rosi: lipid accumulation↑; -GW9662: lipid accumulation↓ |
178 compounds consisting of AMPK activators, PPARγ agonists, and PPARγ antagonists | -1st hit: 7 compounds: adipogenesis↓ in 3D instead of 2D. -2nd hit: 3 compounds: repetitive anti-adipogenic effects in 3D, adiponectin expression↑; Compound #71: pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β)↓. |
None |
| Abbott et al. (2018)78 | Human liquified lipoaspirates from ten subjects with different BMI | -Seeded into silk scaffolds; -Tested in 24-well platforms |
None | AICAR (500 μM): one of exercise mimetics | -Lipolysis↓ in only 3 of the 10 patient samples. -Responsiveness was not correlated with BMI (varied from 22, 23, 23, 26, 30, 32, 32, 33, 33, 51 kg/m2). |
None | |
| T2DM | Park et al. (2019)83 | mice 3T3-L1 preadipocytes and macrophages (RAW264.7) |
-Suspended in alginate hydrogel mixture for 3D bioprinting | Rosi: glucose uptake↑, GLUT4 expression↑, G6PD enzyme activity↓ | 5 PPARγ antagonists: GW9662, BADGE, SR202, FH535, and T0070907 | -1st hit: All 5 antagonists: lipogenesis-related genes and proteins (FABP4, ADIPOQ, PLIN, and PPARγ2)↓. -2nd hit: GW9662 (10 μM): glucose uptake↑, GLUT4 expression↑, G6PD enzyme activity↓. |
C57BL/6ob/ob mice orally administrated GW9662 (300 mg/kg): -Body and fat weights↓. -OGTT↑, ITT↑, HOMA-IR index↓. |
| Park et al. (2020)84 | hADSCs and macrophages (RAW264.7) |
-Suspended in alginate hydrogel mixture for bioprinting of 3D beads; -Loaded in separate wells of 3D co-culture acrylic plates allowing cell interaction |
Metformin and Rosi: glucose uptake↑, adiponectin secretion↑ | 11β-HSD1 inhibitors: KR-1 (mouse-potent enantiomer), KR-2 (human-potent enantiomer) KR-3 (racemic compound) |
-1st hit: KR-1 and KR-3: mouse 11β-HSD1↓; KR-2: human 11β-HSD1↓. -2nd hit: KR-1 and KR-3: glucose uptake↑, GLUT4 expression↑ in mice-derived WAOs; KR-2 and KR-3: glucose uptake↑, GLUT4 expression↑ in human-derived WAOs. |
None | |
| NAFLD | Slaughter et al. (2021)104 | Primary human cardiac preadipocytes and primary human hepatocytes | Incorporated into two-chamber housing system | None | Metformin | Metformin (1mM) for a shortened 7-day treatment: -2D: Cell death. -3D: Steatosis↓ in diabetic, obese, diabetic plus obese, diabetic plus obese and proinflammatory medium. |
Failure in clinical translation: The result dose is above physiological range in clinical application (1-50 μM). |
ADIPOQ: adiponectin; AICAR: 5‐aminoimidazile‐4‐caboxamide‐1‐β‐D‐ribofuranoside; AMPK: adenosine monophosphate-activated protein kinase; BADGE: Bisphenol A diglycidyl ether; BMI: body mass index; FABP4: fatty acid binding protein 4; GLUT4: glucose transporter 4; GW9662: PPARγ antagonist; G6PD: glucose-6-phosphate dehydrogenase; hADSC: human adipose-derived stem cells; HOMA-IR: Homeostatic Model Assessment for Insulin Resistance; IL: interleukin; ITT: insulin tolerance test; KR: compound synthesized at the Korean Research Institute of Chemical Technology; OGTT: oral glucose tolerance test; PLIN: perilipin; PPARγ: peroxisome proliferator-activated receptor gamma; Rosi: rosiglitazone; TNF-α: tumor necrosis factor-alpha; WAO: white adipose organoid; 3D: three-dimensional; 11β-HSD1: 11β-hydroxysteroid dehydrogenase type 1.