Obesity and Aging in the Drosophila Model

摘要

Being overweight increases the risk of many metabolic disorders, but how it affects lifespan is not completely clear. Not all obese people become ill, and the exact mechanism that turns excessive fat storage into a health-threatening state remains unknown. Drosophila melanogaster has served as an excellent model for many diseases, including obesity, diabetes, and hyperglycemia-associated disorders, such as cardiomyopathy or nephropathy. Here, we review the connections between fat storage and aging in different types of fly obesity. Whereas obesity induced by high-fat or high-sugar diet is associated with hyperglycemia, cardiomyopathy, and in some cases, shortening of lifespan, there are also examples in which obesity correlates with longevity. Transgenic lines with downregulations of the insulin/insulin-like growth factor (IIS) and target of rapamycin (TOR) signaling pathways, flies reared under dietary restriction, and even certain longevity selection lines are obese, yet long-lived. The mechanisms that underlie the differential lifespans in distinct types of obesity remain to be elucidated, but fat turnover, inflammatory pathways, and dysregulations of glucose metabolism may play key roles. Altogether, Drosophila is an excellent model to study the physiology of adiposity in both health and disease.