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. Author manuscript; available in PMC: 2016 Oct 22.
Published in final edited form as: Cell. 2015 Oct 22;163(3):560–569. doi: 10.1016/j.cell.2015.10.001

Figure 2. Schematic Illustration of Hypothalamic Control of Negative Energy Metabolism with Low ROS.

Figure 2

(A) In the brain, the hypothalamus contains neuronal populations that control hunger (negative energy balance) and satiety (positive energy balance). Hunger state is promoted by neurons (green) that produce Agouti-related peptide (AgRP) and neuropeptide Y (NPY), as well as GABA. When these neurons are active (hunger, calorie restriction, starvation), systemic metabolism is shifting to lipid metabolism with an overall lower level of mtROS production in all tissues.

(B) The activation of AgRP neurons during negative energy balance is promoted by pathways enabling long-chain fatty acid oxidation in the mitochondria, which is enabled by maintenance of low mtROS generation by engagement of UCP2 and mechanisms that propagate fission and/or proliferation of mitochondria (NRF1, Sirt1, and PGC1α).

(C) UCP2 is believed to function as a conditional mitochondrial uncoupler in the presence of long-chain fatty acids and, as such, reduces mtROS production and overall cellular ROS levels.