Marc Tittgemeyer

Max Planck Institute for Metabolism Research

Translational Neurocircuitry

Regarding the neural circuits in support of adaptive physiological and homeostatic functions, we extend the basic research being pursued at CECAD on metabolic processes with studies on human physiology, clinical diseases and pertaining states.

Research Focus

We investigate how the human brain represents, integrates and prioritizes internal physiological and external environmental signals to initiate adequate behavioural responses with a special focus on circuit-level models, metabolic mechanisms and aging. Thereby, our main research focus concerns the physiological pathways by which peripheral signals are communicated to the brain to interact with reward processing and motivated behaviour.

With the aim to understand the biological pathways mediating individual differences in behavior and risk for (psycho-)pathology implicated in controlling energy homeostasis, we explore the role of metabolic state and motivated behavior in obesity and aging-associated diseases.

Our Goals

Survival under selective pressure is driven by the ability of our brain to use sensory information to our advantage to control physiological needs. In this context, neural circuits receive and integrate external environmental cues and internal metabolic signals to form learned sensory associations, which consequently motivate and adapt our behaviour. The dopaminergic midbrain plays a crucial role in learning adaptive behaviour and is particularly sensitive to peripheral metabolic mediators, including intestinal signal peptides like GLP-1, insulin or leptin.

Recently, the group has demonstrated that adaptive learning is reduced when metabolic sensing is impaired in obesity, leading to disrupted circuit mechanisms of integrating and interpreting sensory information; hence, there is an inadequate sensing of physiological need and dyscalibrated motivational drive. We have furthermore shown that not only metabolic mediators interact with sensory regulation and motivated behaviour but also nutrients directly. Food palatability may act on the dopaminergic reward system to modulate incentive motivation and override homeostatic control, and Western diets can directly affect neurobehavioural adaptations beyond food intake that may increase the risk for subsequent overeating and weight gain.

Building on these achievements, we further focus on the physiological mechanisms by which internal bodily signals are communicated to and sensed by the brain to adapt the organism´s behaviour to its metabolic state and physiological need, especially related to the role of diet-induced neuroinflammation and ageing processes.

Key Publications

  1. DiFeliceantonio, A.G., Coppin, G., Rigoux, L., Thanarajah, S.E., Dagher, A., Tittgemeyer, M.*, and Small, D.M.*(2018). Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward. Cell Metab 28, 33-44.e3. 10.1016/j.cmet.2018.05.018.
  2. Hanssen, R.*, Rigoux, L.*, Albus, K., Kretschmer, A.C., Thanarajah, S.E., Chen, W., Hinze, Y., Giavalisco, P., Steculorum, S.M., Cornely, O.A., Brüning, J.C., Tittgemeyer, M. (2023). Circulating uridine dynamically and adaptively regulates food intake in humans. Cell Rep. Med. 4, 100897. 10.1016/j.xcrm.2022.100897.
  3. Hanssen, R., Rigoux, L., Kuzmanovic, B., Iglesias, S., Kretschmer, A.C., Schlamann, M., Albus, K., Thanarajah, S.E., Sitnikow, T., Melzer, C., Brüning, J.C., Tittgemeyer, M. (2023). Liraglutide restores impaired associative learning in individuals with obesity. Nat. Metab., 1–12. 10.1038/s42255-023-00859-y.
  4. Thanarajah, S.E., Backes, H., DiFeliceantonio, A.G., Albus, K., Cremer, A.L., Hanssen, R., Lippert, R.N., Cornely, O.A., Small, D.M., Brüning, J.C., Tittgemeyer, M.(2019). Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans. Cell Metab 29, 695-706.e4. 10.1016/j.cmet.2018.12.006.
  5. Thanarajah, S.E., DiFeliceantonio, A.G., Albus, K., Kuzmanovic, B., Rigoux, L., Iglesias, S., Hanßen, R., Schlamann, M., Cornely, O.A., Brüning, J.C., Tittgemeyer, M.*, Small, D.M.* (2023). Habitual daily intake of a sweet and fatty snack modulates reward processing in humans. Cell Metab. 35, 571-584.e6. 10.1016/j.cmet.2023.02.015.

*shared contribution