Examining the obesity paradox: A moderating effect of fitness on adipose endocrine function in older adults.

Despite evidence linking obesity with increased mortality, older adults with excessive adiposity seem protected, resulting in a so-called "obesity paradox". Obesity is characterized by leptin resistance, which contributes to increased risk of all-cause mortality. Therefore, lifestyle factors, such as physical fitness, that lower leptin independent of adiposity may be confounding the "obesity paradox". To investigate this, we evaluated whether physical fitness moderated the relationship between leptin and adiposity. We found older adults with higher fitness had lower body mass (r(39) = -0.43, p < 0.01), leptin (r(39) = -0.29, p = 0.03) and inflammation (IL-1β: (r(39)= -0.69, p < 0.01); TNF-α: (r(39)= -0.30, p = 0.03)). Fitness moderated the relationship between leptin and adiposity (F(5, 37) = 3.73, p <  0.01, R2 = 0.33) to reveal the obesity paradox in moderately and high fit individuals (b = 216.24, t(37) = 1.46, p =  0.15; b= -88.10, t(37)= -0.49, p = 0.63) but not in low fit individuals. These results show the link between obesity and mortality may not be dependent on total adiposity, but rather on endocrine function and adipocyte leptin secretion. These results have important implications for older adults struggling to maintain healthy body composition and suggest that fitness may promote overall wellbeing.