Leptin as a Neuroactive Agent

Abstract

Clinical research suggests an important role of leptin in psychiatric illnesses. Given the morbidity associated with mental illness, clinical research on the role of leptin and related novel therapeutic modalities is needed.

The association between leptin and depressive symptoms is modulated by abdominal adiposity

“…Nevertheless, the result of an interactive effect of leptin and waist circumference in predicting depressive symptoms is consistent with the hypothesis that it is not the absolute concentration of leptin that is correlated with mood but rather its ability to induce an effect at the receptor/post-receptor level(Lu, 2007; Zupancic and Mahajan, 2011). In this context, reduced leptin signaling to central nervous systems may be due to both leptin insufficiency in lean subjects or functional resistance-related hyperleptinemia in obese persons.…”

“…From a clinical point of view, these data sustain the idea that the key to understand the pathophysiology of leptin may lie in its function and its impaired central action and not merely in its circulating level. Therefore, in obese depressed patients therapeutic interventions on leptin downstream pathways should target leptin central resistance rather than leptin itself(Lu, 2007; Zupancic and Mahajan, 2011). A recent study(Yamada et al, 2011) showed that leptin homeostatic and antidepressant effect were impaired in the hippocampus of diet-induced obese mice, resulting in a severe depressive state despite hyperleptinemia; diet substitution and weight loss in the obese mice normalized leptin levels and restored the antidepressant effect of leptin.…”

“…In this context a role in depression has been proposed for leptin(Lu, 2007; Zupancic and Mahajan, 2011), the peptide hormone secreted by white adipose tissue that exerts a primary homeostatic function by suppressing nutritional intake and allowing energy expenditure. Leptin receptors are expressed in limbic substrates related to mood regulation (e.g.…”

“…The failure of high levels of leptin to suppress food intake and decrease body weight/adiposity in obese persons is thought to be caused by a mechanism of leptin resistance (similar to the one that links type 2 diabetes and insulin resistance) that blunts leptin central action despite increasing concentrations(Munzberg and Myers, 2005). Based on these observations, it has been hypothesized that is not the absolute leptin concentration but rather reduced leptin signaling to the central nervous system that affects mood(Zupancic and Mahajan, 2011; Lu, 2007). Therefore, hyperleptinemia due to functional resistance in obese persons may represent a phenotype risk for depression similar to leptin insufficiency in lean patients.…”

Association between binge eating disorder and changes in cognitive functioning following bariatric surgery

“…Given evidence that obesity is associated with neurocognitive deficits, such that higher BMIs are associated with greater deficits, the improvement in neurocognitive functioning following bariatric surgery may be due, at least in part, to weight loss associated with the surgical intervention. However, given the effects of bariatric surgery on a number of systems and functions that have been linked with cognitive functioning (e.g., insulin resistance, leptin levels; Ballantyne et al, 2006; Beckman et al, 2010; Park, 2001; Zupancic & Mahajan, 2011), the specific mechanisms underlying these changes remains unclear.…”