CREB is involved in the regulation of POMC processing enzymes andα‐MSH production in the hypothalamus of mice

In experimental obesity, dietary saturated fatty acids affect POMC endopeptidases, resulting in the abnormal production of the neurotransmitters a-melanocyte stimulating hormone (a-MSH) and b-endorphin, thus impacting energy balance. The cAMP response element-binding protein (CREB) is one of the transcription factors that control the expression of POMC endopeptidases; however, it was previously unknown if dietary fats could affect CREB and consequently the expression of POMC endopeptidases.

Here, we used single-cell RNA sequencing analysis, PCR, immunoblot, ELISA and immunofluorescence histological assays to determine the impact of a high-fat diet on the expression and function of hypothalamic CREB and its impact on the melanocortinergic system. The results indicate that CREB is expressed in arcuate nucleus POMC neurons and is activated shortly after the introduction of a high-fat diet. The inhibition of hypothalamic CREB using a short-harpin RNA lentiviral vector resulted in increased diet-induced body mass gain and reduced energy expenditure.