The modulating effect of the androgen receptor on craving in alcohol withdrawal of men is partially mediated by leptin

Abstract

We reported recently that a functional relevant CAG trinucleotide repeat of the androgen receptor influences craving of men in alcohol withdrawal. It is known to modulate serum concentrations of leptin, which affects hypothalamic appetite regulation. Its plasma levels are elevated during chronic alcohol consumption, normalize within periods of abstinence and are associated with craving. The aim of this study was to further elucidate the role of leptin in mediating the effects of the mentioned polymorphism on craving in men undergoing alcohol withdrawal. We included 110 male in-patients who were admitted for detoxification treatment. Each one had an established diagnosis of alcohol dependence according to the DSM-IV. Our results show on the one hand negative associations between the number of CAG repeats and (i) leptin serum levels (Po0.01) and (ii) craving (Po0.05), and on the other hand, a positive association between leptin and craving of man in alcohol withdrawal (Po0.001). The path analysis revealed direct and mediated effects of the number of CAG repeats on alcohol craving, direct effects (r ¼ À0.144) accounting for 60% and indirect, leptin-mediated effects (r ¼ À0.096) accounting for 40% of the total effect. Dysregulation of sexual hormones influences human metabolism and seems to affect leptin homeostasis. This report suggests that the investigated polymorphism mediates its effect on craving of men in alcohol withdrawal mostly through the regulation of leptin. Nevertheless future studies are needed to further explore the functionality of the androgen receptor gene in terms of craving.

DNA methylation of the LEP gene is associated with craving during alcohol withdrawal

“…In human cells in vitro demethylation of the promoter leads to an increase of leptin expression (Melzner et al, 2002). There are different other mechanisms that influence leptin expression in humans like the function of the androgen receptor as transcription factor (Lenz et al, 2010). Our results are in line with these findings showing a significant inverse association between mean promoter methylation and changes of leptin serum levels during withdrawal.…”

“…Results on leptin serum levels from this study population have been included in different analyses (Kraus et al, 2004;Hillemacher et al, 2007a,b;Lenz et al, 2010Lenz et al, , 2012. All study participants gave written informed consent.…”

“…There is evidence that higher serum levels of leptin are positively linked to the extent of craving during intoxication treatment (Kiefer et al, 2001a,b;Hillemacher et al, 2007a,b) and that increasing leptin during abstinence indicates risk for relapse (Kiefer et al, 2005). Moreover, leptin has been shown to be involved in the effects of the androgen receptor and steroid 5-alpha reductase II on craving during alcohol withdrawal (Lenz et al, 2010(Lenz et al, , 2012.…”

Serum NUCB2/nesfatin-1 levels in different stages of alcohol dependence: Is there a relationship with craving?

“…[7] Lenz et al . [35] have suggested that androgen receptor on craving in alcohol withdrawal in men is partially mediated by leptin. Thus, the relationship between craving scores and NUCB2/nesfatin-1 level according to gender seems to be unclear and needs to be studied further.…”

The Relationship of Appetitive, Reproductive and Posterior Pituitary Hormones to Alcoholism and Craving in Humans

“…A significant inverse relation was reported between total and obsessive craving and androgen receptor repeat length such that a greater number of length of repeats was significantly associated with attenuated severe craving in men (Lenz et al 2009). A subsequent study on this group of men in alcohol withdrawal also reported that this polymorphism mediates its effect on craving primarily through regulation of leptin (Lenz et al 2010). …”