Background: An intact hormonal regulation of appetite is crucial for preventing weight gain in a world full of obesogenic temptations. Disrupted signaling of hormonal appetite regulators is often observed in individuals with obesity (BMI ≥ 30 kg/m²) and related diseases, such as type 2 diabetes. Previous research indicates that such disturbances may be induced by weight gain itself, but also other factors such as glucocorticoid excess (e.g. due to stress). However, knowledge regarding the associations between hormonal appetite signals and biological or psychological stress measures is still limited. 

Methods: Data were collected from 67 patients with obesity of which 21% had type 2 diabetes. Psychological stress was assessed with the Perceived Stress Scale (PSS)-14 and biological stress was measured using the average of 24h urine cortisol levels of two consecutive days. Moreover, levels of hormonal appetite regulators (leptin, adiponectin, insulin, FGF21, PP, GIP, PYY, CCK, AgRP and resistin) were measured in serum after an overnight fast. The cross-sectional associations between psychological/biological stress and hormonal appetite regulators were studied by means of linear regression analysis adjusted for pre-defined potential confounders (age, sex and BMI).

Results: Most hormonal appetite regulators were not associated with PSS-14 or 24h urine cortisol levels. However, there was a negative association between FGF21 and PSS-14 (r=-.312, p=.019) which persisted after multivariable adjustment for the potential confounders.

Conclusion: In patients with obesity, higher levels of psychological stress are associated with lower levels of the insulin-sensitizer FGF21, independently of age, sex and BMI. In view of previous evidence showing that glucocorticoids reduce circulating levels of FGF21, we hypothesize that (long-term) psychological stress may interfere with FGF21 signaling via increased HPA-axis activity. Future studies should investigate the directionality of this relation and its potential role in the development of type 2 diabetes.