Welcome to our Monthly Journal Club! Each month I post a paper or two that I have read and find interesting. I use this as a forum for open discussion about the paper in question. Anyone can participate in the journal club, and provide comments/critiques on the paper. This month’s paper is “Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State” by Michael Krashes and colleagues at The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). I will provide a brief overview of the techniques/approaches used to make it more understandable to potential non-expert readers. If I am not familiar with something, I’ll simply say so.

Uncovering the neural populations responsible for appetite, feeding, metabolic control, and hedonic (rewarding/pleasurable) responses to food is essential for crafting new therapies for obesity, anorexia, and sickness-induced (e.g., cancer) appetite suppression. The hypothalamus is a critical structure controlling food intake and appetite, however the distinct roles of specific neural sub-populations in appetite control is not clear. If we can learn the ways different genetically-defined neural populations contribute to feeding, then we can potentially design drugs or other therapies that specifically target only those cells (to have the maximum effect with little off target problems).

The paraventricular hypothalamus (‘around the ventricle’; PVH) is an especially important hypothalamic node in appetite control, illustrated by the fact that lesions of this area cause massive obesity due to large increases in food intake. It is comprised of several neuromodulator populations (all expressing the critical transcription factor SIM1) that can be genetically targeted based on their expression of specific proteins: (1) glucagon-like peptide 1 receptor [Glp1r]; (2) melanocortin-4 receptor [Mc4r], (3) oxytocin [Oxt], and (4) corticotropin-releasing hormone [Crh]. These markers are not clear-cut, and many cells express more than one. Regardless, expression of these primary proteins demonstrates that each of these populations are largely independent from one another. The roles each of these play in appetite, food intake, and metabolism are unclear. Michael Krashes’ team tackled this problem using a variety of techniques including fiber photometry, immunohistochemistry, electrophysiology, and DREADDs.