Figure 8.

Proposed mechanism for the leptin-induced sympathetic outflow in lean and obese mice. In lean mice, leptin reaches the hypothalamus and binds to leptin receptors (LRb) in POMC neurons of the ARH to increase the secretion of α-MSH, which in turn directly activates melanocortin receptors (MC4Rs) in the PVH, DMH, and intramediolateral column (IML). MC4R activation then mediates peripheral sympathetic outflow, probably by both direct and indirect signaling processes, leading to increased expression and activity of mitochondrial UCP-1 in BAT to generate heat. When mice become obese, there is a selective leptin resistance in arcuate neurons (POMC and AgRP neurons), but other brain areas, including the DMH, are still responsive to leptin. The chronic hyperleptinemia found in obesity is able to stimulate leptin receptor expressing neurons to increase sympathetic nervous outflow to iBAT.