Molecular Mechanisms Linking Obesity to Disease in Males and Females

Obesity is the most significant risk factor for most common diseases, including cardiometabolic diseases and cancer. However, there is a difference in fat distribution among obese individuals, which leads to varying disease risks. Males have a more detrimental fat distribution than females and also higher rates of most obesity-related diseases.

However, the pathophysiological mechanisms underlying these differences are not yet known.

Here we will estimate the causal effects of obesity on disease risk in males and females across adulthood by developing and using a new statistical method that utilizes genetic information: time-resolved Mendelian randomization.

We will also determine differences in fat distribution with age and between sexes and identify molecular profiles associated with distinct adipose tissue depots using large-scale body imaging and multi-omics data.

Finally, we will identify molecular mechanisms linking adipose tissue to disease risk by multivariable causal inference.The goal is to provide new knowledge on the relationship between obesity, fat distribution, and disease risk, uncover how these factors contribute to differences in disease and death rates between sexes, and identify new molecular biomarkers for risk assessment in obesity.

The findings will inform precision health interventions and offer novel insights into the pathophysiological mechanisms underlying obesity-related diseases, with implications for public health and disease prevention.