Metabolic signatures and neurophysiological mechanisms of bad food decisions.

Background: Hunger or malnutrition causes insufficient caloric intake which leads to extensive physiological changes up to organ damage and death. Thus, at a certain point, a progressive malnutrition evokes the individual´s inevitable decision to intake food of bad quality to ensure survival. The underlying mechanisms of such a vital decision are, however, barely understood. Our project now aims to gain a holistic understanding of changes that occur in brain-body communication to induce the intake of bad quality food, which is normally avoided. We aim to identify the metabolic signatures, endocrine and neurophysiological mechanisms that trigger bad food decisions.

Methods: To test feeding decisions in Drosophila, individual larvae are exposed to liquid yeast-rich food as reference. On top, the larva´s decision to intake bad quality food is challenged by high amount of bitter or salt added to the yeast solution. During each experiment under certain conditions, e.g. in fed or starved conditions, the number of mouth hook contractions per minute is analyzed which reflects food intake behaviour in Drosophila. Accompanying behavioural studies, we used calcium imaging to investigate response properties of target neurons to stimuli such as quinine (bitter) or NaCl (salt). For this, we express the genetically encoded calcium sensor GCaMP6m in the neurons of interest and analyse calcium transients towards gustatory stimuli presentation.

Results: Our data provide evidence that individuals intuitively avoid the intake of bad quality food. However, this active decision is dependent on the physiological state and thus animals reconsider their decision under starvation ensuring survival. In detail, animals actively ingest salty or bitter food which they normally avoid. Further, our data provide first insights into the underlying mechanisms of decision making as the artificial optogenetic activation (through expression of channelrhodopsin) of octopaminergic neurons leads to the immediate intake of bad food without starvation. These results indicate that octopamine, a neurohormone which is functionally homologue to the vertebrate noradrenaline, is a central regulator of context-dependent feeding decisions. Interestingly, we could show that octopaminergic neurons integrate metabolic signatures as they express specific adipokinetic hormone receptors (adipokinetic hormone is known to be functional homolog to vertebrate glucagon) and insulin receptors.

Conclusions: Our results lead us to the hypothesis that the acceptance of “bad” food is status-dependent, and that octopamine, along with adipokinetic hormone are key molecules in the brain-body communication orchestrating feeding behaviour.

Publication History

Article published online:
18 April 2024