The Impact of Appetite-Regulating Neuropeptide Leptin on Alcohol Use, Alcohol Craving and Addictive Behavior: A Systematic Review of Preclinical and Clinical Data

Abstract

Aims The appetite regulating hormone leptin, which is mainly secreted from adipose tissue, is an important regulator of food intake and modulator of reward-driven behavior. Leptin exerts its biological actions via binding to the leptin receptor, which is expressed in the hypothalamus, but also in the hippocampus, the amygdala and the substantia nigra. In the ventral tegmental area (VTA), leptin attenuates the firing rate of dopaminergic neurons that project to the Nucleus accumbens (NAc), which serves as relay to other brain areas of the “addiction network”, such as the prefrontal cortex. This suggests that leptin plays a role in the processing of rewards in the context of substance use disorders such as alcohol use disorder, especially through attenuation of dopaminergic activity in the mesolimbic reward system. This supports the plausibility of leptin’s potential effects in alcohol use disorder. Methods We searched MEDLINE from 1990 to February 2020. All abstracts were screened for relevance and we only included publications reporting original data with a full text available in English language. Studies that did not report leptin-data, reviews or case reports/series were not included. Results We identified a total of N=293 studies of whom a total of N=55 preclinical and clinical studies met the specified criteria. N=40 studies investigated the effects of alcohol on leptin plasma levels, N=9 studies investigated the effects of leptin on alcohol craving and N=6 studies investigated the effects of leptin on relapse and alcohol consumption. Conclusions In this review of preclinical and clinical data, we assess the role of leptin in alcohol use and the development and maintenance of an alcohol use disorder, alcohol craving and relapse. Integrating the existing preclinical and clinical data on leptin may reveal new and innovative targets for the treatment of substance use disorders in the future.

Leptin Gene and Leptin Receptor Gene Polymorphisms in Alcohol Use Disorder: Findings Related to Psychopathology

“…Our identified haplotype associations with substance use and anxiety measures, along with findings from previous literature (20,21,32,(81)(82)(83)(84)(85) suggest that genetic variations within components of the leptin system (peptide/receptor) may be linked to these psychological and behavioral outcomes. These associations raise interesting questions about how anxiety may be linked to leptin and smoking, however, the causative effects of these associations cannot be delineated.…”

“…We report here that genetic variation at LEP and LEPR was associated with AUD diagnosis, cigarette use, and anxiety. Numerous papers have identified a relationship between leptin and alcohol-related measures [for a recent review, see: (20)], wherein leptin appears to be negatively associated with alcohol craving in current drinkers, and an increase in leptin following alcohol abstinence appears to be positively associated with alcohol craving. Here, we identified only one LEP haplotype to be associated with a diagnosis of current AUD in the European American group but found no relationship with TLFB measures of alcohol drinking or AUDIT score.…”

“…While the role of leptin in addiction remains to be fully confirmed, preclinical and clinical studies suggest that leptin may play a role in addictive behaviors and affective disorders (20,21). Although there are some inconsistencies between studies, several have linked plasma leptin concentrations to alcohol consumption (22)(23)(24) and craving (25)(26)(27)(28)(29)(30).…”

The Role of Nutritional Habits and Moderate Red Wine Consumption in PON1 Status in Healthy Population

“…In this study, we requested that the participants did not change the normal diet that they had; however, we observed a significant decrease (8.7%; p < 0.001) in caloric intake. Some studies have reported that alcohol consumption increases or decreases the blood levels of leptin, the hormone responsible for the sensation of satiety [44][45][46]. The effects of alcohol on leptin depend on the quantity, frequency of ingestion, and type of alcoholic beverage [47][48][49].…”

Factors associated with body mass index changes among older adults: a ten-year follow-up

“…In contrast to the results found in this study, other studies 35 have shown that older people who consume alcohol have lower BMI than those who do not. Because alcohol affects inhibition of brain regions, such as the hypothalamus, large amounts of alcohol may reduce food intake 36 , while limited amounts of alcohol may increase appetite 37 . Also, because alcohol effects on blood can be longlasting in older people, even small amounts of alcohol can exacerbate chronic diseases occurrence and development 38 .…”