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Insulin action in the brain regulates systemic metabolism and cognition. The consumption of an unhealthy diet with increased amounts of saturated long-chain fatty acids and simple carbohydrates can induce insulin resistance with mitochondrial dysfunction in the brain, which leads to increased food intake, obesity and glucose intolerance. Brain insulin resistance can be induced by a various pathways and dysfunctional organelles, including a deteriorated mitochondrial function. We have identified the importance of a functional interplay between brain insulin sensitivity and mitochondrial function. Novel data from our lab have shown that an alteration in this interplay impacts hypothalamic sphingolipid metabolism.
This Master´s thesis project aims at investigating the effect of different sphingolipids on hypothalamic insulin signaling and mitochondrial function. This work should help to better understand the impact of an specifically altered sphingolipid metabolism on insulin sensitivity to properly regulate metabolism. All in vitro models have been already generated and the successful candidate will analyze the neuronal sphingolipid metabolism by using a diverse set of biochemical and molecular biological tools and collaborate with research groups in Berlin.
1. R. Hauffe et al., HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue. Mol Metab53, 101276 (2021).
3. A. Kleinridders et al., Leptin regulation of Hsp60 impacts hypothalamic insulin signaling. J Clin Invest123, 4667-4680 (2013).
4. M. Schell et al., Interplay of Dietary Fatty Acids and Cholesterol Impacts Brain Mitochondria and Insulin Action. Nutrients12, (2020).
5. M. Schell, K. Wardelmann, A. Kleinridders, Untangling the effect of insulin action on brain mitochondria and metabolism. J Neuroendocrinol, e12932 (2021).
6. K. Wardelmann et al., Insulin action in the brain regulates mitochondrial stress responses and reduces diet-induced weight gain. Mol Metab, (2019).
7. K. Wardelmann et al., Central Acting Hsp10 Regulates Mitochondrial Function, Fatty Acid Metabolism, and Insulin Sensitivity in the Hypothalamus. Antioxidants (Basel)10, (2021).
Tasks:
The applicant will be part of an international, diverse research team, surrounded by enthusiastic researchers and an exciting atmosphere. The candidate will have the opportunity to present his/her research data at a national conference and will work closely with an experienced Postdoc.
If you are interested in this position, please contact:
Prof. Dr. André Kleinridders
E-Mail: kleinriddersuuni-potsdampde
Universität Potsdam
Institut für Ernährungswissenschaften
Molekulare und Experimentelle Ernährungsmedizin
Arthur-Scheunert-Allee 114-116
14558 Nuthetal
Insulin action in the brain regulates systemic metabolism and cognition. The consumption of an unhealthy diet with increased amounts of saturated long-chain fatty acids and simple carbohydrates can induce insulin resistance in the brain, which leads to increased food intake, obesity and glucose intolerance. Brain insulin resistance can be induced by a variety of different molecules, with diverse signaling cascades. Negative modulators of insulin resistance are certain serine/threonine kinases (e.g. JNK) and phosphatases. We have identified a novel phosphatase, which regulates insulin signaling and alters metabolism. So far, it is unclear how this phosphatase impacts on metabolism.
This Master´s thesis project aims at investigating the molecular mechanism of the phosphatase on neuronal metabolism. We have already generated CRISPR/Cas9 Knockout neurons as a in vitro model to address the research task. The student should cultivate these cells and analyze the neuronal metabolism by using a diverse set of biochemical and molecular biological tools.
1. A. Kleinridders, H. A. Ferris, W. Cai, C. R. Kahn, Insulin action in brain regulates systemic metabolism and brain function. Diabetes63, 2232-2243 (2014).
2. A. Kleinridders, E. N. Pothos, Impact of Brain Insulin Signaling on Dopamine Function, Food Intake, Reward, and Emotional Behavior. Curr Nutr Rep8, 83-91 (2019).
3. M. Schell et al., Interplay of Dietary Fatty Acids and Cholesterol Impacts Brain Mitochondria and Insulin Action. Nutrients12, (2020).
Tasks:
The applicant will be part of an international, diverse research team, surrounded by enthusiastic researchers and an exciting atmosphere. The candidate will have the opportunity to present his/her research data at a national conference and will work closely with an experienced PhD student.
If you are interested in this position, please contact:
Prof. Dr. André Kleinridders
E-Mail: kleinriddersuuni-potsdampde
Universität Potsdam
Institut für Ernährungswissenschaften
Molekulare und Experimentelle Ernährungsmedizin
Arthur-Scheunert-Allee 114-116
14558 Nuthetal
University of Potsdam
Molecular and Experimental Nutritional Medicine
Arthur-Scheunert.Alle 155
14558 Nuthetal
Tel.: +49 33200 88-5528
Fax: +49 33200 88-5573
E-Mail: idiesseluuni-potsdampde