Autophagy and Obesity-Related Lung Disease

Abstract

Obesity-related disease is a significant source of premature death and economic burden globally. It is also a common comorbidity in patients suffering from lung disease, affecting both severity and treatment success. However, this complex association between obesity and the lung is poorly understood. Autophagy is a self-recycling homeostatic process that has been linked to beneficial or deleterious effects, depending on the specific lung disease. Obesity affects autophagy in a tissue-specific manner, activating autophagy in adipocytes and impairing autophagy in hepatocytes, immune cells, and pancreatic β-cells, among others. Obesity is also characterized by chronic low-grade inflammation that can be modulated by the pro- and antiinflammatory effects of the autophagic machinery. Scant evidence exists regarding the impact of autophagy in obesity-related lung diseases, but there are communal pathways that could be related to disease pathogenesis. Important signaling molecules in obesity, including IL-17, leptin, adiponectin, NLRP3 inflammasome, and TLR-4, have been implicated in the pathogenesis of lung disease. These mediators are known to be modulated by autophagy activity. In this perspective, we highlight the recent advances in the understanding of autophagy in obesity-related conditions, as well as the potential mechanisms that can link autophagy and obesity in the pathogenesis of lung disease.

Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

“…Obesity leads not only to an increase in adipose tissue mass but also to the infiltration of proinflammatory cells and secretion of inflammatory cytokines [1, 2]. Therefore, obesity is characterized by low-grade inflammation in local and systemic sites as demonstrated by robust secretion of proinflammatory cytokines, including IL-6, as well as active recruitment of leukocytes [3].…”

Normal lung development needs self-eating

“…Over the previous decade, there has been a surge of interest in autophagy, as both a cell and organism survival mechanism during starvation as well as a potential therapeutic target in various human diseases, including cancer and fibrosis. Since 2010, research into the role of autophagy in the lung has dramatically increased and focused on diverse areas, including chronic respiratory disease, fibrosis, lung cancer, inflammation-mediated injury, and emphysema (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Now, Yeganeh and colleagues (16) provide compelling evidence that intrinsic autophagy is required for normal progression of lung development.…”

Modulation of autophagy in human diseases strategies to foster strengths and circumvent weaknesses

“…Dysregulation of tubular autophagy and mitophagy in diabetic nephropathy through activation of the mTOR signaling pathway 91,92 Acute kidney injury Defect PRKAA1, ATG7, STAT3, NQO1, MTOR Dysfunction of autophagy in the elimination of ROS during AKI 93,94 Endocrine system Obesity Defect Atg7, Mtor, Ulk1, Defect in degenerating redundant fat in cells [95][96][97] Diabetes mellitus Defect/ active MTOR, ATG5, ATG7…”