Improvements in Long-Term Appetite-Regulating Hormones in Response to a Combined Lifestyle Intervention for Obesity

Abstract

Altered levels of hormonal appetite regulators have been observed in obesity (BMI ≥ 30.0 kg/m2), most prominently increases of insulin and leptin (indicating resistance) as well as decreases of adiponectin - all of which are long-term energy regulators and adiposity signals. Disrupted signaling of these hormones may have detrimental effects on metabolism, but may also promote weight gain. Weight loss is often accompanied by normalizations of long-term adiposity signals, but findings concerning short-term appetite regulators after weight loss vary across interventions (e.g. very low calorie diets vs. exercise). Moreover, it is debated whether such weight-loss-induced hormonal changes may reflect a disposition for weight regain. Here, we investigated changes of long- and short-term appetite signals in response to an intensive 75-week combined lifestyle intervention (CLI) comprising a normocaloric healthy diet, physical activity and psychotherapy to promote improved long-term weight management. For 39 patients, data on fasting serum levels of appetite-regulating hormones (leptin, insulin, adiponectin, GIP, PP, PYY, CCK, FGF21) were available. Hormone levels were correlated to BMI at baseline (T0) and compared across three time points: T0, T1 (after 10 weeks; initial weight loss) and T2 (after 75 weeks; weight loss maintenance). T0-T1 hormone changes were correlated to BMI changes between T1 and T2 to investigate whether hormonal alterations during initial weight loss are associated with weight regain. At T0, hormone levels were not associated with BMI. BMI decreased significantly from T0 (40.13 kg/m2 ± 5.7) to T1 (38.2 ± 5.4, p < .001) which was maintained at T2 (38.2 kg/m2 ± 5.9, p < .001). There were no significant changes in GIP, PP, PYY, CCK and FGF21. Leptin decreased from T0 (44.9 ng/nl ± 15.3) to T1 (33 ng/nl ± 14.8, p < .001) and T2 (38.6 ng/nl ± 16.0, p < .01), just like insulin which was significantly decreased at T1 (123 pmol/l ± 65, p < .05) and T2 (128 pmol/l ± 64, p < .05) compared to T0 (160 pmol/l ± 80). Adiponectin did not change between T0 (3.36 ug/ml ± 2.1) and T1 (3.2 ug/ml ± 2.1), but was increased at T2 (3.7 ug/ml ± 2.9, p < .01) compared to T1. T0-T2 BMI decrease correlated positively with T0-T2 decreases in leptin (r = .667, p < .001), insulin (rho = .535, p < .001) and increases of adiponectin (r = .412, p < .01), but no other hormone. T0-T1 hormone changes did not predict T1-T2 BMI changes. Thus, a 75-week CLI was associated with beneficial changes in the long-term energy regulators adiponectin, leptin and insulin, but no changes in short-term appetite-regulating hormones were observed despite significant weight loss. Initial changes in appetite-regulating hormones were not associated with subsequent weight regain. Overall, our data suggest that a CLI does not lead to adverse changes in appetite regulation, but rather long-term improvements such as e.g. increased leptin and insulin sensitivity.