Endocrine Abstracts

Similar to individual cells, hypothalamic neural circuits profit from intracellular pathways known to work as fuel sensors to maintain energy balance.

The mammalian target of rapamycin complex 1 (mTORC1) signaling cascade is among the latest intracellular fuel-sensing pathways to be implicated in the hypothalamic regulation of energy balance.

mTORC1 activity is found in both NPY/AgRP- and POMC-producing neurons of the arcuate nucleus. Activation of mTORC1 and phosphorylation of its downstream targets are critical intracellular steps mediating the anorectic actions of both nutrients, such as amino acids, and hormonal signals like leptin. Interestingly, mTORC1 activity in the mediobasal hypothalamus varies as a function of the cell type and of the particular stimulus employed, as opposed to responding in a uniform manner to nutritional and hormonal changes. Furthermore, a link exists between intracellular fatty acid metabolism and mTORC1 and recent studies have shown that high-fat feeding and diet-induced obesity are conditions leading to the impairment of mTORC1 activity in the hypothalamus.

Here we will give an overview of the known functions of this pathway in the context of energy balance regulation and we will further present downstream mechanisms that we have recently identified to be engaged by mTORC1 for the control of food intake and body weight.

Taken together, these findings lead to conclude that mTORC1 is a highly conserved fuel sensor, which integrates signals from both stored and immediately available fuels and whose activity in the hypothalamus triggers adaptive feeding responses.

Declaration of interest: The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.