Obesity, defined as a body mass index (BMI) greater than or equal to 30, is one of the major health burdens of the 21st century as it contributes to the growing prevalence of its related comorbidities, including insulin resistance, type2 diabetes and other metabolic disorders. Growing evidence suggests the development of systemic low-grade chronic inflammation creates metabolic complications in obese individuals. Specifically, chronic inflammation in fat tissues is considered to be a crucial risk factor for the development of insulin resistance and type2 diabetes. However, the triggers for adipose tissue inflammation are still poorly defined. Currently, obesity-induced adipose tissue expansion is thought to provide a plethora of intrinsic signals such as adipocyte death, hypoxia, and mechanical stress, capable of initiating the inflammatory response. Immune dysregulation in fat tissues results in a chronic low-grade inflammation characterized by increased proinflammatory cytokines like IL-6 and TNFa and reduced anti-inflammatory cytokines like adipokines in blood circulation as well as infiltration and activation of innate and adaptive immune cells in white fat tissues in obese individuals. Interestingly, however, not all individuals meeting the criteria for obesity exhibit metabolic complications. A subset of obese individuals may be considered as having metabolically healthy obesity with no evidence of existing metabolic complications. It is generally considered that visceral fats are bad while subcutaneous fats are good without rationalized scientific reasoning.

 

Preliminary work from my lab has shown that excess adipocyte hypertrophy causes ripping-off of the mesothelium encompassing fat tissues. These sterile injuries compromise the barrier functions of the mesothelium separating adipocytes from the peritoneal cavity. Because this unique location of visceral fat tissues (i.e. within hypoxic peritoneal environment), the breach in the mesothelial barrier further causes low-grade chronic inflammation due to direct communications of adipocytes with hypoxic peritoneal environment. We hypothesize that chronic low-grade inflammation associated with obesity is caused by sterile injuries of the mesothelium due to hypertrophy of adipocytes in visceral fat tissues and subsequent direct communications between hypoxic peritoneal environment and visceral fat tissues. To address this hypothesis, we will perform 3D confocal analysis on white fat tissues and RNA transcriptome analysis in high-fat diet induced mouse models Our hypothesis provides a scientific reasoning as to why the visceral fat deposition is worse than the subcutaneous fat deposition for human health.