In view of the sizeable informational gap in the role of the FSTL1 protein in obesity, the main objectives of this study were to (1) analyze circulating FSTL1 protein levels in morbidly and super obese (OB) and nonobese (non-OB) individuals, (2) explore the 3′ UTR of the FSTL1 gene using bioinformatic tools to locate genetic variants responsible for the gain or loss of specific miRNA binding sites, and (3) analyze the genotype frequencies of selected SNPs in the context of FSTL1 protein level, obesity status, and other anthropometric parameters in an OB and non-OB Central-European population. This evidence concerns the gene FSTL1 and obesity due to melanocortin 4 receptor deficiency.