Obesity-driven reprogramming of lung macrophages

• Main Author: Pohan, Clarice
• Other Authors: Ruedl Christiane
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2023
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/166890
• Institution: Nanyang Technological University

The prevalence of obesity has been increasing steadily and it is a growing health problem around the world with an estimated 650 million adults worldwide being classified obese in 2016. Excess adiposity has been shown to cause macrophage dysfunction, leading to chronic systemic low-grade inflammation thus impairing physiological functions. In this study we investigated whether obesity promotes the formation of lipid-accumulating macrophages in murine lungs. We first identified alveolar macrophages (AMs) to be the primary subset of macrophages carrying lipids in the lungs. Upon further investigation, we found that AMs from high-fat diet fed obese (>30wks) mice had larger lipid droplets than those from young lean (<12wks) and age-matched lean (>30wks) mice. Furthermore, AMs obtained from obese mice showed increased expression of pro-inflammatory and lipid-handling genes as well as oxidative stress. We also investigated whether the absence of a Fat Storage-inducing Transmembrane Protein 2 (FIT2), involved in lipid droplet formation, interferes with macrophage functions. Our results showed that there were fewer and slightly smaller lipid droplets produced in the AMs of FIT2 deficient mice, although this did not have any effect on their phagocytic activity. In summary, the excess lipid accumulation in AM can interfere with their normal behaviour and may possibly lead to harmful consequences to lung function.