Targeting new neurocircuits for appetite modulation and obesity management

Obesity is a continuously growing public health problem, and in 2016, more than 1.9 billion adults wereoverweight or obese.

According to data produced by the WHO (World Health Organisation), in 2013, 53%of the world´s adult population was overweight and in Sweden the corresponding figure was 19%.

By 2030,24% of our population is expected to be severely overweight.Currently, there are no long-term satisfactorytreatments for obesity.The central nervous system regulates body energy status, and the hypothalamus is the master regulator ofenergy homeostasis.

The disruption of the hypothalamic cell activity and metabolic signaling results indysregulation in energy homeostasis, leading to obesity and subsequent comorbidities i.e., diabetes, stroke,Alzheimer´s disease. The role of deep brain dopamine functions in movement and food reward is known.

However, thehypothalamic projections to deep brain regions and the potential role in food intake regulation have neverbeen studied.

Using chemogenetic tools and retrograde targeting, I discovered a new neurocircuitry, and theactivation of this neurocircuitry powerfully initiates feeding in mice on standard chow diet feedingconditions and I will assess whether silencing could suppress the appetite in obese mice.

Identifying gene expression signature patterns of new projection cells may provide novel therapeutic targetsfor future pharmacological interventions and designing novel cell-targeted gene therapies in obesity.