The strengths of the present study include: first, it is a large sample size cohort of people with overweight and obesity, reporting circulating levels of BDNF, SPARC, FGF-21 and GDF-15 before and after obesity therapy; second, we demonstrated changes in circulating levels of the four cytokines in response to several anti-obesity treatments, including LEI with or without pharmacotherapy or bariatric/metabolic surgery; and third, the study participants were Asian in origin where this kind of study is still lacking. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.