High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ Body Mass Index (BMI)
Obesity is a complex and incompletely understood disease, but current drug screening strategies mostly rely on immature in vitro adipose models which cannot recapitulate it properly. To address this issue, we developed a statistically validated high-throughput screening model by seeding human mature...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2022-01-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X21002401 |
| _version_ | 1797203940893261824 |
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| author | Fiona Louis Yoshihiro Sowa Shiro Kitano Michiya Matsusaki |
| author_facet | Fiona Louis Yoshihiro Sowa Shiro Kitano Michiya Matsusaki |
| author_sort | Fiona Louis |
| collection | DOAJ |
| description | Obesity is a complex and incompletely understood disease, but current drug screening strategies mostly rely on immature in vitro adipose models which cannot recapitulate it properly. To address this issue, we developed a statistically validated high-throughput screening model by seeding human mature adipocytes from patients, encapsulated in physiological collagen microfibers. These drop tissues ensured the maintenance of adipocyte viability and functionality for controlling glucose and fatty acids uptake, as well as glycerol release. As such, patients’ BMI and insulin sensitivity displayed a strong inverse correlation: the healthy adipocytes were associated with the highest insulin-induced glucose uptake, while insulin resistance was confirmed in the underweight and severely obese adipocytes. Insulin sensitivity recovery was possible with two type 2 diabetes treatments, rosiglitazone and melatonin. Finally, the addition of blood vasculature to the model seemed to more accurately recapitulate the in vivo physiology, with particular respect to leptin secretion metabolism. |
| first_indexed | 2024-04-24T08:27:19Z |
| format | Article |
| id | doaj.art-cbefa8c91c9449b596931607f745e385 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:27:19Z |
| publishDate | 2022-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-cbefa8c91c9449b596931607f745e3852024-04-16T21:46:25ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-01-017227241High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ Body Mass Index (BMI)Fiona Louis0Yoshihiro Sowa1Shiro Kitano2Michiya Matsusaki3Osaka University, Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, 2-1 Yamadaoka, Suita Osaka, 565-0871, JapanKyoto Prefectural University of Medicine, Department of Plastic and Reconstructive Surgery, Graduate School of Medical Sciences, Kamigyo-ku Kajii-cho, Kawaramachi-Hirokoji, Kyoto, 602-8566, Japan; Corresponding author. Kyoto, 602-8566, Kamigyo-ku Kajii-cho, Kawaramachi-Hirokoji, Japan.Osaka University, Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, 2-1 Yamadaoka, Suita Osaka, 565-0871, Japan; TOPPAN PRINTING CO., LTD., Technical Research Institute, 4-2-3 Takanodaiminami, Sugito-machi, Saitama, 345-8508, JapanOsaka University, Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, 2-1 Yamadaoka, Suita Osaka, 565-0871, Japan; Osaka University, Graduate School of Engineering, Department of Applied Chemistry, 2-1 Yamadaoka, Suita Osaka, 565-0871, Japan; Corresponding author. Osaka, 565-0871, 2-1 Yamadaoka, Suita, Japan.Obesity is a complex and incompletely understood disease, but current drug screening strategies mostly rely on immature in vitro adipose models which cannot recapitulate it properly. To address this issue, we developed a statistically validated high-throughput screening model by seeding human mature adipocytes from patients, encapsulated in physiological collagen microfibers. These drop tissues ensured the maintenance of adipocyte viability and functionality for controlling glucose and fatty acids uptake, as well as glycerol release. As such, patients’ BMI and insulin sensitivity displayed a strong inverse correlation: the healthy adipocytes were associated with the highest insulin-induced glucose uptake, while insulin resistance was confirmed in the underweight and severely obese adipocytes. Insulin sensitivity recovery was possible with two type 2 diabetes treatments, rosiglitazone and melatonin. Finally, the addition of blood vasculature to the model seemed to more accurately recapitulate the in vivo physiology, with particular respect to leptin secretion metabolism.http://www.sciencedirect.com/science/article/pii/S2452199X21002401Mature vascularized adipose tissue reconstructionHigh-throughput drug-screening modelObesityBMIDiabetes |
| spellingShingle | Fiona Louis Yoshihiro Sowa Shiro Kitano Michiya Matsusaki High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ Body Mass Index (BMI) Bioactive Materials Mature vascularized adipose tissue reconstruction High-throughput drug-screening model Obesity BMI Diabetes |
| title | High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ Body Mass Index (BMI) |
| title_full | High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ Body Mass Index (BMI) |
| title_fullStr | High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ Body Mass Index (BMI) |
| title_full_unstemmed | High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ Body Mass Index (BMI) |
| title_short | High-throughput drug screening models of mature adipose tissues which replicate the physiology of patients’ Body Mass Index (BMI) |
| title_sort | high throughput drug screening models of mature adipose tissues which replicate the physiology of patients body mass index bmi |
| topic | Mature vascularized adipose tissue reconstruction High-throughput drug-screening model Obesity BMI Diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X21002401 |
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