Exploring the mediating roles of diet and physical activity in the association between different obesity phenotypes and risk of depression: A cox survival analysis approach

Although obesity has been linked to an increased risk of depression, the risk associated with different obesity phenotypes remain unclear, as does the role of lifestyle behaviors. Participants from the UK Biobank who were free of depression at the baseline and had complete data on body composition and metabolism-related measures were selected and followed up. Multivariable Cox models were employed to assess the risk of developing depression according to obesity phenotypes. Mediation analyses were conducted to evaluate the potential mediating effects of diet and physical activity in this association. Among 391,781 participants, a total of 20,027 incident depression was recorded after a median follow-up period of 13.39 years. Our study revealed that different obesity phenotypes increased the risk of depression to varying degrees. Compared with healthy non-obese individuals, those with BMI ≥30 kg/m² only had the lowest risk of depression (HR: 1.15, 95 %CI: 1.04, 1.28), and then followed by central obesity (HR: 1.60, 95 %CI: 1.51, 1.70), metabolically unhealthy obesity (HR: 1.63, 95 %CI: 1.56, 1.70). Sarcopenic obesity results in the highest risk of depression among these four phenotypes (HR: 1.86, 95 %CI: 1.40, 2.46). Both physical activity and diet mediated the effect of the four obesity phenotypes on the risk of depression. In the relationship between BMI ≥30 only and depression, physical activity mediated for 2.49 % and diet mediated for 1.60 %. Between metabolically unhealthy obesity and depression, physical activity mediated for 7.08 % and diet mediated for 1.86 %. This set of data was 5.29 % and 1.47 % in the relationship between central obesity and depression, and 6.22 % and 1.25 % in the relationship between sarcopenic obesity and depression. Subgroup analyses revealed that the female with obesity (including four types) had a higher risk of depression compared to the male, whereas individuals aged 60 years or older and those who were former or current smokers with obesity (except sarcopenic obesity) exhibited a lower risk of depression. These findings provide a basis for the prevention of obesity-depression comorbidity in obese patients.