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...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.展开更多
基金The authors thank Nippon Ham Foods Ltd for their kind donation of collagen.This research was supported by a Kakenhi Grant-in-Aid for Early-Career Scientists(70838523)as well as a grant from the Japanese Ministry of Education,Culture,Sports,Science and Technology(18K09488).
文摘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.
