A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo

被引:7
作者
Lovfors, William [1 ,2 ]
Ekstrom, Jona [1 ]
Jonsson, Cecilia [3 ]
Stralfors, Peter [3 ]
Cedersund, Gunnar [1 ,4 ]
Nyman, Elin [1 ]
机构
[1] Linkoping Univ, Dept Biomed Engn, Linkoping, Sweden
[2] Linkoping Univ, Dept Math, Linkoping, Sweden
[3] Linkoping Univ, Dept Biomed & Clin Sci, Linkoping, Sweden
[4] Linkoping Univ, Ctr Med Image Sci & Visualizat CMIV, Linkoping, Sweden
基金
瑞典研究理事会; 欧盟地平线“2020”;
关键词
INSULIN-RESISTANCE; MODEL; PHOSPHODIESTERASE; DESENSITIZATION; ACTIVATION; MECHANISM; OBESITY;
D O I
10.1371/journal.pone.0261681
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Lipolysis and the release of fatty acids to supply energy fuel to other organs, such as between meals, during exercise, and starvation, are fundamental functions of the adipose tissue. The intracellular lipolytic pathway in adipocytes is activated by adrenaline and noradrenaline, and inhibited by insulin. Circulating fatty acids are elevated in type 2 diabetic individuals. The mechanisms behind this elevation are not fully known, and to increase the knowledge a link between the systemic circulation and intracellular lipolysis is key. However, data on lipolysis and knowledge from in vitro systems have not been linked to corresponding in vivo data and knowledge in vivo. Here, we use mathematical modelling to provide such a link. We examine mechanisms of insulin action by combining in vivo and in vitro data into an integrated mathematical model that can explain all data. Furthermore, the model can describe independent data not used for training the model. We show the usefulness of the model by simulating new and more challenging experimental setups in silico, e.g. the extracellular concentration of fatty acids during an insulin clamp, and the difference in such simulations between individuals with and without type 2 diabetes. Our work provides a new platform for model-based analysis of adipose tissue lipolysis, under both non-diabetic and type 2 diabetic conditions.
引用
收藏
页数:22
相关论文
共 41 条
[1]   The impact of mathematical modeling on the understanding of diabetes and related complications [J].
Ajmera, I. ;
Swat, M. ;
Laibe, C. ;
Le Novere, N. ;
Chelliah, V. .
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 2013, 2 (07)
[2]   Fatty Acids, Obesity and Insulin Resistance [J].
Arner, Peter ;
Ryden, Mikael .
OBESITY FACTS, 2015, 8 (02) :147-155
[3]  
Arrestam O., bioRxiv, V2021, DOI DOI 10.1101/2021.11.04.467307
[4]   Insulin Signaling in Type 2 Diabetes EXPERIMENTAL AND MODELING ANALYSES REVEAL MECHANISMS OF INSULIN RESISTANCE IN HUMAN ADIPOCYTES [J].
Brannmark, Cecilia ;
Nyman, Elin ;
Fagerholm, Siri ;
Bergenholm, Linnea ;
Ekstrand, Eva-Maria ;
Cedersund, Gunnar ;
Stralfors, Peter .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (14) :9867-9880
[5]   Putting the pieces together in diabetes research: Towards a hierarchical model of whole-body glucose homeostasis [J].
Cedersund, Gunnar ;
Stralfors, Peter .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2009, 36 (01) :91-104
[6]   Conclusions via unique predictions obtained despite unidentifiability - new definitions and a general method [J].
Cedersund, Gunnar .
FEBS JOURNAL, 2012, 279 (18) :3513-3527
[7]   The 'Digital Twin' to enable the vision of precision cardiology [J].
Corral-Acero, Jorge ;
Margara, Francesca ;
Marciniak, Maciej ;
Rodero, Cristobal ;
Loncaric, Filip ;
Feng, Yingjing ;
Gilbert, Andrew ;
Fernandes, Joao F. ;
Bukhari, Hassaan A. ;
Wajdan, Ali ;
Martinez, Manuel Villegas ;
Santos, Mariana Sousa ;
Shamohammdi, Mehrdad ;
Luo, Hongxing ;
Westphal, Philip ;
Leeson, Paul ;
DiAchille, Paolo ;
Gurev, Viatcheslav ;
Mayr, Manuel ;
Geris, Liesbet ;
Pathmanathan, Pras ;
Morrison, Tina ;
Cornelussen, Richard ;
Prinzen, Frits ;
Delhaas, Tammo ;
Doltra, Ada ;
Sitges, Marta ;
Vigmond, Edward J. ;
Zacur, Ernesto ;
Grau, Vicente ;
Rodriguez, Blanca ;
Remme, Espen W. ;
Niederer, Steven ;
Mortier, Peter ;
McLeod, Kristin ;
Potse, Mark ;
Pueyo, Esther ;
Bueno-Orovio, Alfonso ;
Lamata, Pablo .
EUROPEAN HEART JOURNAL, 2020, 41 (48) :4556-+
[8]   Reduction of a biochemical model with preservation of its basic dynamic properties [J].
Dano, Sune ;
Madsen, Mads F. ;
Schmidt, Henning ;
Cedersund, Gunnar .
FEBS JOURNAL, 2006, 273 (21) :4862-4877
[9]   From PDE3B to the regulation of energy homeostasis [J].
Degerman, Eva ;
Ahmad, Faiyaz ;
Chung, Youn Wook ;
Guirguis, Emilia ;
Omar, Bilal ;
Stenson, Lena ;
Manganiello, Vincent .
CURRENT OPINION IN PHARMACOLOGY, 2011, 11 (06) :676-682
[10]   MEIGO: an open-source software suite based on metaheuristics for global optimization in systems biology and bioinformatics [J].
Egea, Jose A. ;
Henriques, David ;
Cokelaer, Thomas ;
Villaverde, Alejandro F. ;
MacNamara, Aidan ;
Danciu, Diana-Patricia ;
Banga, Julio R. ;
Saez-Rodriguez, Julio .
BMC BIOINFORMATICS, 2014, 15