Abstract

Excess consumption of high-fat diet (HFD) is likely to result in obesity and increases the predisposition to associated health disorders. Drosophila melanogaster has emerged as an important model to study the effects of HFD on metabolism, gut function, behavior, and ageing. In this study, we investigated the effects of HFD on physiology and behavior of female flies at different time-points over several weeks. We found that HFD decreases lifespan, and also with age leads to accelerated decline of climbing ability in both virgins and mated flies. In virgins HFD also increased sleep fragmentation with age. Furthermore, long-term exposure to HFD results in elevated adipokinetic hormone (AKH) transcript levels and an enlarged crop with increased lipid stores. We detected no long-term effects of HFD on body mass, or levels of triacylglycerides (TAG), glycogen or glucose, although fecundity was diminished. However, one week of HFD resulted in decreased body mass and elevated TAG levels in mated flies. Finally, we investigated the role of AKH in regulating effects of HFD during aging. Both with normal diet (ND) and HFD, Akh mutant flies displayed increased longevity compared to control flies. However, both mutants and controls showed shortened lifespan on HFD compared to ND. In flies exposed to ND, fecundity is decreased in Akh mutants compared to controls after one week, but increased after three weeks. However, HFD leads to a similar decrease in fecundity in both genotypes after both exposure times. Thus, long-term exposure to HFD increases AKH signaling, impairs lifespan and fecundity and augments age-related behavioral senescence.

Highlights

  • Intake of high-fat diet (HFD) is likely to result in obesity, which in turn increases the predisposition to cardiovascular disease, diabetes, cancer, and other metabolic disorders (Bray and Popkin, 1998; Dietrich et al, 2013; Hill et al, 2000; Musselman and Kühnlein, 2018; O'Brien and Dixon, 2002; Szendroedi and Roden, 2009; van Herpen and Schrauwen-Hinderling, 2008)

  • It is known that the first few days after hatching there is residual larval fat body which serves as a nutrient resource while the fly commences feeding and adjusts to its adult metabolism (Aguila et al, 2007)

  • Summary and conclusions In summary, our data suggest that exposure to HFD reduces lifespan, and accelerates age-related deterioration of behaviors such as negative geotaxis and sleep patterns, it leads to reduced fecundity

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Summary

Introduction

Intake of high-fat diet (HFD) is likely to result in obesity, which in turn increases the predisposition to cardiovascular disease, diabetes, cancer, and other metabolic disorders (Bray and Popkin, 1998; Dietrich et al, 2013; Hill et al, 2000; Musselman and Kühnlein, 2018; O'Brien and Dixon, 2002; Szendroedi and Roden, 2009; van Herpen and Schrauwen-Hinderling, 2008). Studies have emerged on the effect of HFD on health and physiology of Drosophila (Birse et al, 2010; Driver and Cosopodiotis, 1979; Heier and Kühnlein, 2018; Heinrichsen and Haddad, 2012; Huang et al, 2020; Jung et al, 2018; Musselman and Kühnlein, 2018; Rivera et al, 2019; Stobdan et al, 2019; Tatar et al, 2014; Toprak et al, 2020; Trinh and Boulianne, 2013; von Frieling et al, 2020; Woodcock et al, 2015). Most of these studies have investigated effects of relatively short exposure to HFD, ranging between one and three weeks, some determined the effect of HFD on lifespan (Heinrichsen and Haddad, 2012; Rivera et al, 2019; Woodcock et al, 2015)

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