Regulation of Hunger-Stimulating AgRP Neurons by microRNA – PROTFEED

Appetite-related brain disorders such as anorexia, bulimia, and binge eating disorder have become major mental health problems in modern societies, particularly affecting the younger population. These disorders arise from the dysregulation of neuronal circuits responsible for controlling physiological hunger. Conversely, the unprecedented availability of inexpensive, calorie-dense food—rich in carbohydrates and fats—has disrupted the brain’s reward system, leading to obesity.

Most obese patients eventually develop cardiovascular diseases and type 2 diabetes, collectively referred to as metabolic syndrome, which significantly increases the risk of cancer and reduces life expectancy.

The hypothalamus plays a central role in maintaining the balance between hunger and satiety. Within it, Agouti-related peptide (AgRP) neurons are critical for regulating feeding behavior, as they strongly stimulate hunger in animals. However, the mechanisms controlling AgRP neuronal activity, particularly at the protein regulation level, remain poorly understood.

Recent findings from the research team have shown that microRNAs (miRNAs)—small, non-coding regulatory RNAs—within the arcuate nucleus of the hypothalamus can strongly modulate the activity of AgRP neurons by altering protein translation, ultimately leading to obesity in mice.

The goal of this project is to investigate the molecular and functional properties of AgRP neurons in which regulatory microRNAs are selectively deleted.

The expected results will:

1. Provide fundamental insights into the function of AgRP neurons, particularly regarding neuropeptide expression and key protein regulation, and

2. Lay the groundwork for the future development of targeted therapies for eating disorders controlled by the brain.