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• Leptin and its receptor ObR play a critical role in Parkinson's disease etiology and progression via its neuroinflammatory properties. • Experimental work is needed to further elaborate leptin signaling in disease onset and progression. • Large-scale in-human studies of leptin and other adipokines taking into account multiple covariates are warranted. • In view of the dual character of leptin (neuroprotective versus pro-inflammatory), other adipokines (e.g., ghrelin, adiponectin) may represent better targets for PD. An increasing body of experimental evidence implicates a relationship between immunometabolic deterioration and the progression of Parkinson's disease (PD) with a dysregulation of central and peripheral neuroinflammatory networks mediated by circulating adipokines, in particular leptin. We screened the current literature on the role of adipokines in PD. Hence, we searched known databases (PubMed, MEDLINE/OVID) and reviewed original and review articles using the following terms: "leptin/ObR", "Parkinson's disease", "immune-metabolism", "biomarkers" and "neuroinflammation". Focusing on leptin, we summarize and discuss the existing in vivo and in vitro evidence on how adipokines may be protective against neurodegeneration, but at the same time contribute to the progression of PD. These components of the adipose brain axis represent a hitherto underestimated pathway to study systemic influences on dopaminergic degeneration. In addition, we give a comprehensive update on the potential of adjunctive therapeutics in PD targeting leptin, leptin-receptors, and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanisms of action and the value of central and peripheral adipose-immune-metabolism molecular phenotyping in order to develop and validate the differential roles of different adipokines as potential therapeutic target for PD patients. [ABSTRACT FROM AUTHOR]