Adipokines provide an outstanding role in the comprehensive etiology of obesity and may link adipose tissue dysfunction to further metabolic and cardiovascular complications. Although several adipokines have been identified in terms of their physiological roles, many regulatory circuits remain unclear and translation from experimental studies to clinical applications has yet to occur. Nevertheless, due to their complex metabolic properties, adipokines offer immense potential for their use both as obesity-associated biomarkers and as relevant treatment strategies for overweight, obesity and metabolic comorbidities. To provide an overview of the current clinical use of adipokines, this review summarizes clinical studies investigating the potential of various adipokines with respect to diagnostic and therapeutic treatment strategies for obesity and linked metabolic disorders. Furthermore, an overview of adipokines, for which a potential for clinical use has been demonstrated in experimental studies to date, will be presented. In particular, promising data revealed that fibroblast growth factor (FGF)-19, FGF-21 and leptin offer great potential for future clinical application in the treatment of obesity and related comorbidities. Based on data from animal studies or other clinical applications in addition to obesity, adipokines including adiponectin, vaspin, resistin, chemerin, visfatin, bone morphogenetic protein 7 (BMP-7) and tumor necrosis factor alpha (TNF-α) provide potential for human clinical application.

Purpose: Adipokines may play an important role in the complex etiology of human obesity and its metabolic complications. Here, we analyzed the relationship between 15 adipokines, eating behavior and body-mass index (BMI). Methods: The study included 557 participants of the Sorbs (62.1% women, 37.9% men) and 3101 participants of the population-based LIFE-Adult cohorts (53.4% women, 46.4% men) who completed the German version of the Three-Factor-Eating Questionnaire to assess the eating behavior types cognitive restraint, disinhibition and hunger. Serum levels of 15 adipokines, including adiponectin, adipocyte fatty acid-binding protein (AFABP), angiopoietin-related growth factor (AGF), chemerin, fibroblast growth factor (FGF)-19, FGF-21, FGF-23, insulin-like growth factor (IGF)-1, interleukin (IL) 10, irisin, progranulin, vaspin, pro-neurotensin (pro-NT), pro-enkephalin (PENK) and leptin were measured. Based on significant correlations between several adipokines with different eating behavior items and BMI, we conducted mediation analyses, considering the eating behavior items as potential mediation variable towards BMI. Results: Here, we found that the positive association between chemerin, AFABP or leptin and BMI in Sorbian women was mediated by higher restraint or disinhibited eating, respectively. Additionally, in Sorbian women, the negative relation between IGF-1 and BMI was mediated by higher disinhibition and the positive link between AGF and BMI by lower disinhibition. In Sorbian men, the negative relationship between PENK and BMI was mediated by lower disinhibition and hunger, whereas the negative relation between IGF-1 and BMI was mediated by higher hunger. In the LIFE-Adult women´s cohort, associations between chemerin and BMI were mediated by decreased hunger or disinhibition, respectively, whereas relations between PENK and BMI were fully mediated by decreased disinhibition. Conclusion: Our study suggests that adipokines such as PENK, IGF-1, chemerin, AGF, AFABP and leptin might affect the development of obesity by directly modifying individual eating behavior. Given the observational nature of the study, future experimental or mechanistic work is warranted.

Background and hypothesis: The endogenous opioid proenkephalin (PENK) has been identified as an independent risk marker for acute cardiovascular diseases and acute kidney injury. However, its regulation, its association with other cardiometabolic markers and its prognostic role in patients with chronic kidney disease (CKD) have not been thoroughly investigated. Methods: PENK serum levels were cross-sectionally related to renal and cardiometabolic markers across three large cohorts (total N = 4722), including the Leipzig-CKD cohort (N = 581), as well as the population-based LIFE-Adult (N = 3093) and Sorbs (N = 1048) cohort. Furthermore, a longitudinal analysis was performed in the Leipzig-CKD cohort to assess the association between circulating PENK levels at baseline and a composite 4-point major adverse renal events (4P-MAKE) endpoint comprising incident or worsening kidney disease, development of kidney failure (KF) requiring kidney replacement therapy or kidney transplantation, and renal deaths. Results: In the entire cross-sectional cohort (N = 4722), PENK levels were strongly and inversely correlated with markers of renal function, i.e. estimated glomerular filtration rate (eGFR), creatinine and urinary albumin–creatinine ratio. In multivariable analysis, eGFR was the strongest, independent and inverse predictor of circulating PENK levels after adjustment for age and sex, as well as markers of obesity, glucose intolerance, dyslipidemia and inflammation. Multivariable Cox regression analysis revealed that baseline circulating PENK levels were strongly associated with an increased risk of the 4P-MAKE over a median follow-up of 8.7 years. Each doubling of PENK levels was associated with a >2-fold increase in the risk of developing 4P-MAKE, even after adjusting for various clinical and metabolic variables. PENK provided added value for predicting adverse renal outcomes. Conclusions: PENK levels are strongly, independently, and inversely associated with renal function in cross-sectional analysis. Furthermore, baseline circulating PENK levels are predictive of a 4P-MAKE in patients and added independent, prognostic value for identification of patients at risk for adverse renal outcomes.