Parental dietary protein-to-carbohydrate ratio affects offspring lifespan and metabolism in drosophila

Abstract

Non-genetic inheritance of metabolic state over multiple generations has been widely reported in insects. The present study uses the fruit fly, Drosophila melanogaster, to assess whether lifespan, physiological traits and metabolism are affected by the dietary protein-to-carbohydrate ratio (P:C) of the prior adult generation. Groups of parental flies were fed diets with different P:C ratios. Their progeny groups were raised on the same diet so the only variable in the experiments was the diet fed to the parents. Parental P:C affected the lifespan of female offspring, however had no impact on F1 males survival. Low parental P:C increased feeding rate in progeny. An increase in the P:C ratio from 0.03 to 0.65 decreased the levels of body glucose and trehalose in the offspring and a similar tendency was observed in the levels of circulating hemolymph glucose and trehalose. Offspring also accumulated less triglycerides but more glycogen when parents were fed a low P:C diet. Our study indicates that the parental dietary P:C ration has a strong impact on the lifespan, reproduction, appetite and metabolism in the offspring generation.

Introduction

The link between nutrition and aging has been studied extensively using Drosophila melanogaster as a model organism (Mair et al., 2005; Min et al., 2007). Numerous studies from recent years have been specifically focused on the influence of parental diet on offspring physiology, metabolism and lifespan. However, the molecular mechanisms that underlie these associations remain undiscovered. Several hypotheses have been proposed to explain this process including programming mechanisms such as epigenetics (Buescher et al., 2013; Vaiserman et al., 2017). Drosophila melanogaster is a genetically tractable model organism for studying physiological processes affected by parental dietary conditions because of the high conservation of metabolic pathways among animal species. Altering the maternal or paternal diet, or both, is a simple procedure that can be used to determine the effect of diet on the offspring physiology in Drosophila (Brookheart and Duncan, 2016).

Dietary condition is a key determinant of aging and lifespan. Many studies have used Drosophila to investigate the mechanisms involved in dietary restriction and over-nutrition and their complex influence on lifespan (Tatar et al., 2014). For example, it has been demonstrated that the balance between macronutrients has a more significant impact than total calorie intake on Drosophila lifespan and physiology (Lee et al., 2008; Lushchak et al., 2012, 2014; Skorupa et al., 2008; Simpson and Raubenheimer, 2009). Lifespan regulation by diet composition was shown to be achieved through modulation of the activities of conserved signaling pathways such as TOR and AMPK in experiments that used either dietary or pharmacological interventions (Broughton et al., 2005; Lushchak et al., 2017; Piskovatska et al., 2018; Vaiserman et al., 2016; Wullschleger et al., 2006). Furthermore, developmental conditions are also important determinants of longevity in fruit flies and other species (Vaiserman et al., 2018).

Substantial evidence has also suggested a tight correlation between parental nutrition and offspring health (Barker, 1990; Hales and Barker, 1992; Ravelli et al., 1998; Kaati et al., 2002; Pembrey et al., 2006) and shown that this type of nutritional programming can persist across generations. Several factors have been identified that can mediate the impact of parental diet on the physiology of offspring including epigenetic gene regulation, endoplasmic reticulum stress, and mitochondrial disruption (Bruce et al., 2009; Carone et al., 2010; Wu et al., 2010, Wu et al., 2015). Epigenetic control is the most plausible mechanism to explain the effects of parental nutrition on offspring life-history traits. Epigenetic modifications including DNA methylation, histone modification, and non-coding DNA based mechanisms (Xia and de Belle, 2016) are heritable across generations without causing changes in DNA sequence, and they alter the expression of specific genes. Using Drosophila as a model system, a paternal contribution to metabolic programming was also demonstrated (Valtonen et al., 2012; Ost et al., 2014; Aldrich and Maggert, 2015). Parental diet in Drosophila influenced reproduction and, as a result, had a strong impact on offspring health (Matzkin et al., 2013; Colines et al., 2015; Vijendravarma et al., 2010). The dietary composition provided to each parent had a complex impact on the offspring and the combined influence of the diets of both parents lent a further complexity to offspring health (Brookheart and Duncan, 2016).

In the present work, we studied the effects of dietary protein-to-carbohydrate (P:C) ratio provided to parents on the physiology, metabolism and lifespan of offspring. We found that low a P:C diet increased offspring appetite. In addition, higher amounts of circulating sugars and glycogen storage in offspring were observed when parents were fed a low P:C diet. We also found that high sucrose consumption decreased F1 female survival. We demonstrated strong dependence of physiological and metabolic parameters of both generations, which significantly are differ in the frames of one of three variables – parental P:C ratio, sex and their interaction (Table 3).