Western diet modulates reward processing in humans

Western diets rich in fat and sugar promote excess calorie intake and weight gain; however, the underlying mechanisms are unclear. Despite a well-documented association between obesity and altered brain dopamine function, it remains elusive whether these alterations are (1) pre-existing, increasing the individual susceptibility to weight gain, (2) secondary to obesity or (3) directly attributable to repeated exposure to western diet.

To close this gap, in a collaborative effort by a team of various CECAD researcher lead by Profs Marc Tittgemeyer, Jens C. Brüning and Oliver A. Cornely, we performed a randomized, controlled trial (NCT05574660) with normal-weight participants exposed to a high-fat/high-sugar snack or a low-fat/low-sugar snack for eight weeks in addition to their regular diet. The high-fat/high-sugar intervention decreased the preference for low-fat food while increasing brain response to food and associative learning independent of food cues or reward. These alterations were independent of changes in body weight and metabolic parameters, indicating a direct effect of high-fat, high-sugar foods on neurobehavioral adaptations that may increase the risk for overeating and weight gain.

Circulating uridine dynamically and adaptively regulates food intake in humans

Feeding behavior must be continuously adjusted to match energy needs. Recent discoveries in murine models identified uridine as a regulator of energy balance. Here,  in a collaborative effort by a team of various CECAD researcher lead by Profs Marc Tittgemeyer, Jens C. Brüning and Oliver A. Cornely, we explore its contribution to the complex control of food intake in humans by administering a single dose of uridine monophosphate (UMP; 0.5 g or 1g) to healthy participants in two placebo-controlled studies designed to assess food behavior (registration: DRKS00014874). We establish that endogenous circulating uridine correlates with hunger and ensuing food consumption. It also dynamically decreases upon caloric ingestion, prompting its potential role in a negative feedback loop regulating energy intake. We further demonstrate that oral UMP administration temporarily increases circulating uridine and — when within the physiological range — enhances hunger and caloric intake proportionally to participants’ basal energy needs. Overall, uridine appears as a potential target to tackle dysfunctions of feeding behavior in humans.

Liraglutide restores impaired associative learning in obesity
Survival under selective pressure is driven by the ability of our brain to use sensory information to our advantage to control physiological needs. To that end, 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 (DA) midbrain plays a crucial role in learning adaptive behaviour and is particularly sensitive to peripheral metabolic mediators, including intestinal signal peptides, such as glucagon-like peptide 1 (GLP-1). 

In a collaborative effort by a team of various CECAD researcher lead by Profs Marc Tittgemeyer, Jens C. Brüning and Oliver A. Cornely, we demonstrate that adaptive learning is reduced when metabolic sensing is impaired in obesity, as indexed by reduced insulin sensitivity. Treatment with the GLP-1 receptor agonist liraglutide normalises impaired learning about sensory associations in obese humans. Collectively, the trial, which was proactively registered at https://clinicalsite.org/trial/2688/en, reveals that GLP-1 receptor activation modulates associative learning in obese humans via its central effects within the mesoaccumbens pathway. These findings provide evidence for how metabolic signals can act as neuromodulators to adapt our behaviour to bodily state, and GLP-1 receptor agonists work in clinics.

Promising new diagnostic method for invasive fungal infections
Novel diagnostic tests to identify invasive fungal infections provide chronically ill patients, such as those with diabetes or leukemia, with new therapeutic perspectives. In patients with compromised immune systems, fungi cause infections that affect the brain or lungs and can prove very difficult to diagnose. In 2014, a national team of scientists around Prof. Oliver A. Cornely from the CECAD Cluster of Excellence at the University of Cologne and the University Hospital achieved a break- through, by using fungus-reactive T cells in a new test procedure.