After weight loss intervention, we observed significant improvements in BM, BMI, body fat Raf inhibition mass (% and kg), visceral and subcutaneous fat, insulin concentration, HOMA-IR, QUICKI, total cholesterol and triglycerides. Indeed, short- and long-term interventions increased the free fat mass (%) (Table 1Table 1). Based on the adipokine and neuropeptide data, we verified increases in adiponectin concentration and adiponectin/leptin

ratio with a concomitant reduction in alpha-MSH concentration. The leptin concentration decreased, while the orexigenic factors (ghrelin and AgRP) increased after 1 year. When we analyzed the AgRP from 6 months to 1 year of intervention, a significant increase was observed (Table 2Table 2). After weight loss intervention, we observed significant improvements in BM, BMI, body fat mass (% and kg), visceral and subcutaneous fat, insulin concentration, HOMA-IR, QUICKI, total cholesterol and triglycerides, similar to the trend observed in the normoleptinemic patients. Only long-term (1 year) treatment

was able to promote a significant increase in free fat mass (%) (Table 1). The group with hyperleptinemia exhibited a significant increase in adiponectin, NPY concentration and adiponectin/leptin ratio as well as a reduction in leptin and NPY/AgRP ratio with short-term intervention. After one year, this group presented a significant increase in adiponectin/leptin ratio and in AgRP concentration, Autophagy animal study with a reduction in the NPY/AgRP ratio (Table 2). GBA3 It is important to note that hyperleptinemic patients presented lower adiponectin/leptin ratio, alpha-MSH and ghrelin concentration at baseline. Indeed, the NPY/AgRP ratio was higher compared with that observed in the non-hyperleptinemic group. We found positive correlations between leptin concentrations and BMI and body fat mass (%) at baseline,

in the entire group (Fig. 1a and b). On the other hand, the leptin concentrations were negatively correlated with free fat mass (%) and alpha-MSH (Fig. 2a and b). Negative correlations between adiponectin/leptin ratio and total cholesterol and LDL-c were confirmed at baseline only in hyperleptinemic patients (Fig. 3a and b). As shown in Table 3Table 3, stepwise multiple linear regression analysis was performed with leptin concentration as the dependent variable. α-MSH and body fat mass (%) were the independent predictors to explain leptin concentration in the present study. Obesity has been shown to cause resistance or reduced sensitivity to several hormones, including leptin and adiponectin. Obese individuals appear to have higher sympathetic nervous system (SNS) activity; however, the metabolic response to SNS stimulation appears reduced in this population. This finding suggests that, in obesity, any compensatory effect of the SNS on metabolism to increase energy expenditure may not occur, rendering weight loss more difficult [8] and [33].