Leptin is a hormone that is secreted by fat and signals the need to stop eating and increase energy expenditure via leptin receptors (LepR). Various hunger and reward centers in the brain contain different LepR expressing neurons. The primary leptin center is the well-studied arcuate nucleus. Other hypothalamic nuclei are less abundant in leptin receptor but also essential in encoding leptin’s actions. The composition of these LepR neurons have not been well understood.

In their recently published paper in Science Reports, Nefeli Kakava and colleagues from the UMC Utrecht Brain Center explore the scarce LepR population in the lateral hypothalamus. This population is known for its effects on food intake and food reward, and may be defective in eating disorders. The authors successfully capture the transcriptome of these neurons using TRAP-Seq. Exploration of their molecular profile confirms the expression of diverse neuropeptides and receptors. Microscopy analysis reveal their diverse spatial expression patterns. Moreover, they unravel new markers that could have significant role in energy balance. They also explore what is the transcriptional response of these neurons to energy deficit.

“I am excited that we have successfully managed to capture RNA from this very rare albeit significant population of leptin responsive cells and hope our findings inspire new research”

Nefeli obtained her PhD in 2020 as part of the Adan lab, where she developed viral vector tools to target and manipulate the activity of brain cells involved in food reward and energy balance. In collaboration with the Basak lab, she has profiled the hypothalamic LepR cells using TRAP-Seq and single cell genomics techniques.