The adipocyte and the adipose tissue
The adipose tissue performs a multitude of different functions, including both metabolic and hormonal functions. For example, the adipose tissue stores excess energy in the form of fat inside the adipocytes, and release this fat when there is a need for energy in the body. These mechanisms of storing or releasing energy is controlled by e.g. insulin and catecholamines (such as adrenaline). In addition to the metabolic control, the adipocyte can also exert a hormonal control. Example of such control is the release of leptin that regulate hunger, and adiponectin which increases the sensitivity of cells to insulin. In our group, we work with modelling the adipocyte and the adipose tissue on both a cellular scale and on a whole-body scale, in multiple species such as humans and rodents. Additionally, we have modelled the impact of different medication in the different scales.
Signalling on a cellular scale
We have investigated intracellular signalling of the adipocyte over the last decades, in collaboration with the labs of (among others): Peter Strålfors, Charlotta Olofsson, and Karin Stenkula. Together we have unraveled key mechanisms of both insulin and catecholamine signalling. The figure above shows a representation of the most up-to-date intracellular model available (modified from a figure in the same article).
Some key publications regarding intracellular adipocyte signalling are:
- Cedersund G, Roll J, Ulfhielm E, Danielsson A, Tidefelt H, Strålfors P. Model-based hypothesis testing of key mechanisms in initial phase of insulin signaling. PLoS Comput Biol. 2008 Jun 20;4(6):e1000096.
- Brännmark C, Nyman E, Fagerholm S, Bergenholm L, Ekstrand EM, Cedersund G, et al. Insulin Signaling in Type 2 Diabetes: Experimental and Modeling Analyses Reveal Mechanisms of Insulin Resistance in Human Adipocytes. Journal of Biological Chemistry. 2013 Apr 5;288(14):9867–80.
- Bergqvist N, Nyman E, Cedersund G, Stenkula KG. A systems biology analysis connects insulin receptor signaling with glucose transporter translocation in rat adipocytes. J Biol Chem. 2017 Jul 7;292(27):11206–17.
- Rajan MR, Nyman E, Kjølhede P, Cedersund G, Strålfors P. Systems-wide Experimental and Modeling Analysis of Insulin Signaling through Forkhead Box Protein O1 (FOXO1) in Human Adipocytes, Normally and in Type 2 Diabetes. J Biol Chem. 2016 Jul 22;291(30):15806–19.
- Lövfors W, Jönsson C, Olofsson CS, Nyman E, Cedersund G. A comprehensive mechanistic model of adipocyte signaling with layers of confidence. bioRxiv. 2022. p. 2022.03.11.483974.
Signalling on a tissue and whole body scale.
In addition to modelling the intracellular adipocyte signalling, we have also modelled the connection of the adipose tissue scale. On a tissue level, it is possible to model the functions of the adipose tissue with the impact to other organs. E.g. how meals impact the glucose uptake and lipolysis of the adipose tissue. Such modelling have sometimes been done based on from arterio-venous data, a technique that measures the difference in the blood content before and after it goes through an organ (illustrated in the figure above, reused from the masters thesis by Kajsa Tunedal). For this modelling, we have collaborated with the labs of (among others): Fredrik Karpe, Natal van Riel and Peter Strålfors.
Some key publications regarding intracellular adipocyte signalling are:
- Nyman E, Brännmark C, Palmér R, Brugård J, Nyström FH, Strålfors P, et al. A hierarchical whole-body modeling approach elucidates the link between in vitro insulin signaling and in vivo glucose homeostasis. J Biol Chem. 2011 Jul 22;286(29):26028–41.
- Sips FLP, Nyman E, Adiels M, Hilbers PAJ, Strålfors P, van Riel NAW, et al. Model-Based Quantification of the Systemic Interplay between Glucose and Fatty Acids in the Postprandial State. PLOS ONE. 2015 Sep 10;10(9):e0135665.
- Tunedal K. Mathematical modeling of fatty acid metabolism during consecutive meals and fasting : New insights into fatty acid regulation based on arterio-venous data. Linköping University, Department of Biomedical Engineering and Linköping University - Department of Biomedical Engineering / Linköping University, Department of Biomedical Engineering and Linköping University - Department of Biomedical Engineering; 2021. p. 30.
- Lövfors W, Ekström J, Jönsson C, Strålfors P, Cedersund G, Nyman E. A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo. PLOS ONE. 2021 Dec 31;16(12):e0261681.
- Simonsson C, Lövfors W, Bergqvist N, Nyman E, Gennemark P, Stenkula KG, et al. A multi-scale in silico mouse model for insulin resistance and humanoid type 2 diabetes. bioRxiv. 2021. p. 2021.05.19.443124.
- Herrgårdh T, Li H, Nyman E, Cedersund G. An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow. Frontiers in Physiology. 2021;12:701.