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Review
. 2018 Oct 26;9(11):1096.
doi: 10.1038/s41419-018-1129-1.

Leptin in depression: a potential therapeutic target

Tongtong Ge  1 , Jie Fan  1 , Wei Yang  1 , Ranji Cui  2 , Bingjin Li  3
Affiliations
Review

Leptin in depression: a potential therapeutic target

Tongtong Ge et al. Cell Death Dis. .

Abstract

Leptin, produced and secreted by white adipose tissue, plays a critical role in regulating body weight, food intake, and energy metabolism. Recently, several studies have identified an underlying role for leptin in regulation of mood and cognition via regulation of synaptic changes in the brain that have been associated with antidepressant-like actions. Brain neural plasticity occurs in response to a range of intrinsic and extrinsic stimuli, including those that may mediate the effects of antidepressants. Neural plasticity theories of depression are thought to explain multiple aspects of depression and the effects of antidepressants. It is also well documented that leptin has effects on neural plasticity. This review summarizes the recent literature on the role of leptin in neural plasticity in order to elaborate the possible mechanism of leptin's antidepressant-like effects. Recent findings provide new insights into the underlying mechanisms of neural plasticity in depression. Leptin may influence these mechanisms and consequently constitute a possible target for novel therapeutic approaches to the treatment of depression.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Leptin’s effect on hippocampal synaptic plasticity.
Activation of LepRb can trigger PI3K/Akt and AMPK/Akt signaling. Both pathways can subsequently inhibit GSK3β activity. PI3K stimulation can enhance NMDA-dependent LTD and stimulate AMPA receptor exocytosis, which contributes to potentiation of excitatory synaptic transmission. Another critical event is mTOR activation, which promotes a synthesis of synaptic protein synthesis and synaptogenesis
Fig. 2
Fig. 2. Leptin activates multiple signaling pathways that potentiate neuroprotection, cell survival, and proliferation.
Leptin binds to LepRb and activates the PI3K/Akt signaling pathway. Activating LepRb also stimulates the MAPK-signaling pathway. Both pathways promote neuroprotection, cell survival, and proliferation. The stimulation of PI3K/Akt decreases GSK-3β activity by phosphorylating GSK-3, promoting the expression of cell proliferation genes. Activation of the LepRb leads to CREB phosphorylation and initiation of CREB-dependent transcription, which also enhances cell proliferation genes. CREB cAMP response element-binding protein
See this image and copyright information in PMC

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