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Research Interest:

The metabolic syndrome is complex and multifactorial, as obesity correlates with, but in itself is a relatively poor predictor for the development of metabolic dysfunction. In contrast, body fat distribution, and other assessments of adipocyte function, are much better predictors for the development of insulin resistance, dyslipidemia and the metabolic syndrome. Various human and animal studies have indicated that storage of triglycerides in subcutaneous versus visceral fat has beneficial metabolic effects. This is especially true in individuals where adipose tissue expansion is primarily driven by increasing the number of adipocytes within the fat depots (hyperplasia), rather than storing lipids in already existing adipocytes (hypertrophy). The factors regulating adipose tissue expansion as well as the development of local and systemic inflammation and insulin resistance remain incompletely understood. However, it is becoming increasingly clear that systems physiology approaches, combining studies and interactions of various organs using cell and molecular biology as well as mouse genetics and computational approaches are essential to progress in our understanding of complex diseases such as the metabolic syndrome. Our main research interest is to uncover the molecular network regulating adipose tissue expansion to find novel approaches to dissociate obesity from insulin resistance and type 2 diabetes.

Project Title:

Dissociating obesity from insulin resistance and type 2 diabetes

 

Project Description:

We previously studied adipose tissue heterogeneity [1,2] to understand the contribution of adipocyte precursor cells to “healthy” adipose tissue expansion. Moreover, we recently demonstrated that adipocyte/ extracellular matrix interaction is important to regulate adipose function in general and insulin action specifically [3]. Building upon these data and our ongoing research projects on immune cell and nerve function in adipose tissue expansion we aim to study the role of the vasculature as niche for adipocyte precursors but also as gatekeeper for the various hormonal and nutritional in- and outputs of adipose tissue. To this end, we aim to establish novel ex-vivo tissue printing technologies to study endothelial/ (pre)-adipocyte interactions in detail and combine this with studies in transgenic mice to better understand the role of the vasculature in promoting unrestricted adipose tissue growth.

Publications:

[1] Suwandhi L, Altun I, Karlina R, Miok V., Wiedemann T., Fischer D, Walzthoeni T, , Lindner C, Boettcher A, Heinzmann SS, Israel A, Braun A, Pramme-Steinwachs I, Burtscher I, Schmitt-Kopplin P, Heinig M, Elsner M, Lickert H, Theis F, Ussar S, (2021) Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population, Nature Communications, 12(1):1588.

[2]Karlina R, Lutter D, Schoettl T, Schorpp K, Israel A, Cero C, Johnson JW,  Kapser-Fischer I, Keipert S, Feuchtinger A, Graf E, Strom T, Walch A, Cypess AM, Ussar S, (2020), Identification and characterization of distinct murine brown adipocyte subtypes in C57BL/6J mice, Life Science Alliance 4 (1): e202000924 

[3]Ruiz-Ojeda FJ, Wang J, Bäcker T, Krueger M, Zamani S, Rosowski S, Gruber T, Feuchtinger A, Schulz TJ, Fässler R, Müller TD, García-Cáceres C, Meier M, Blüher M, Ussar S, (2021), Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis, Molecular Metabolism 7:45:101147