scholarly journals A ‘phenotypic hangover’ – the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome of Drosophila melanogaster

2017 ◽  
Author(s):  
Amy J. Osborne ◽  
Peter K. Dearden

AbstractThe Developmental Origins of Health and Disease (DOHaD) hypothesis predicts that early-life environmental exposures can be detrimental to later-life health, and that mismatch between the pre- and postnatal environment may contribute to the growing non-communicable disease (NCD) epidemic. Within this is an increasingly recognised role for epigenetic mechanisms; epigenetic modifications can be influenced by, e.g., nutrition, and can alter gene expression in mothers and offspring. Currently, there are no whole-genome transcriptional studies of response to nutritional alteration. Thus, we sought to explore how nutrition affects the expression of genes involved in epigenetic processes in Drosophila melanogaster. We manipulated Drosophila food macronutrient composition at the F0 generation, mismatched F1 offspring back to a standard diet, and analysed the transcriptome of the F0 – F3 generations by RNA-sequencing. At F0, the altered (high protein, low carbohydrate, HPLC) diet increased expression of genes involved in epigenetic processes, with coordinated downregulation of genes involved in immunity, neurotransmission and neurodevelopment, oxidative stress and metabolism. Upon reversion to standard nutrition, mismatched F1 and F2 generations displayed multigenerational inheritance of altered gene expression. By the F3 generation, gene expression had reverted to F0 (matched) levels. These nutritionally-induced gene expression changes demonstrate that dietary alteration can upregulate epigenetic genes, which may influence the expression of genes with broad biological functions. Further, the multigenerational inheritance of the gene expression changes in F1 and F2 mismatched generations suggests a predictive adaptive response (PAR) to maternal nutrition. Our findings may help to understand the interaction between maternal diet and future offspring health, and have direct implications for the current NCD epidemic.

2006 ◽  
Vol 34 (6) ◽  
pp. 1138-1140 ◽  
Author(s):  
A.J. Bingham ◽  
L. Ooi ◽  
I.C. Wood

Cardiac hypertrophy is an increase in the size of cardiac myocytes to generate increased muscle mass, usually driven by increased workload for the heart. Although important during postnatal development and an adaptive response to physical exercise, excessive hypertrophy can result in heart failure. One characteristic of hypertrophy is the re-expression of genes that are normally only expressed during foetal heart development. Although the involvement of these changes in gene expression in hypertrophy has been known for some years, the mechanisms involved in this re-expression are only now being elucidated and the transcription factor REST (repressor element 1-silencing transcription factor) has been identified as an important repressor of hypertrophic gene expression.


Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 33
Author(s):  
Sofie De Groef ◽  
Tom Wilms ◽  
Séverine Balmand ◽  
Federica Calevro ◽  
Patrick Callaerts

Obesity is a chronic disease affecting millions of people worldwide. The fruit fly (Drosophila melanogaster) is an interesting research model to study metabolic and transcriptomic responses to obesogenic diets. However, the sex-specific differences in these responses are still understudied and perhaps underestimated. In this study, we exposed adult male and female Dahomey fruit flies to a standard diet supplemented with sugar, fat, or a combination of both. The exposure to a diet supplemented with 10% sugar and 10% fat efficiently induced an increase in the lipid content in flies, a hallmark for obesity. This increase in the lipid content was more prominent in males, while females displayed significant changes in the glycogen content. The strong effects of the diets on the ovarian size and number of mature oocytes were also present in females exposed to diets supplemented with fat and a combination of fat and sugar. In both males and females, the fat body morphology changed and was associated with an increase in the lipid content of fat cells in response to the diets. The expression of metabolism-related genes also displayed a strong sexually dimorphic response under normal conditions and in response to the sugar and/or fat-supplemented diets. Here, we showed that the exposure of adult fruit flies to an obesogenic diet containing both sugar and fat allowed studying sexual dimorphism in metabolism and the expression of genes regulating metabolism.


2019 ◽  
Vol 78 (3) ◽  
pp. 305-312 ◽  
Author(s):  
Mark A. Burton ◽  
Karen A. Lillycrop

Non-communicable diseases (NCD) such as type-2 diabetes and CVD are now highly prevalent in both developed and developing countries. Evidence from both human and animal studies shows that early-life nutrition is an important determinant of NCD risk in later life. The mechanism by which the early-life environment influences future disease risk has been suggested to include the altered epigenetic regulation of gene expression. Epigenetic processes regulate the accessibility of genes to the cellular proteins that control gene transcription, determining where and when a gene is switched on and its level of activity. Epigenetic processes not only play a central role in regulating gene expression but also allow an organism to adapt to the environment. In this review, we will focus on how both maternal and paternal nutrition can alter the epigenome and the evidence that these changes are causally involved in determining future disease risk.


2019 ◽  
Vol 10 (5) ◽  
pp. 587-594
Author(s):  
Abdel Halim Harrath ◽  
Abdulkarem Alrezaki ◽  
Saleh H. Alwasel ◽  
Abdelhabib Semlali

AbstractWe sought to examine whether rat maternal food restriction (MFR) affects the expression of steroidogenesis-related genes Cyp19, Cyp17a1, Insl3 and Gdf-9 in the ovaries of offspring from the first (FRG1) and second (FRG2) generations at pre-pubertal age (week 4) and during adulthood (week 8). At week 4, MFR significantly increased the expression of RNAs for all analyzed genes in both FRG1 and FRG2 females, which may indicate that MFR affects the onset of the reproductive lifespan, by inducing early pubertal onset. At week 8, the Cyp19 gene was still upregulated in MRF-subjected animals (Cyp19: P=0.0049 and P=0.0508 in FRG1 and FRG2, respectively), but MFR induced a significant decrease in Cyp17 and Gdf-9 gene expression in the offspring of both FRG1 and FRG2 females when compared with the controls (Cyp17: P=0.0018 and P=0.0016, respectively; Gdf-9: P=0.0047 and P=0.0023, respectively). This suggests that females at week 8, which should normally be in their optimal reproductive capacity, experience premature ovarian aging. At week 4, the activation of Cyp19 and Cyp17 was higher in the FRG1 ovaries than in the FRG2 ovaries, whereas the extent of Insl3 and Gdf-9 activation was lower in the FRG1 ovaries. This may indicate that FRG2 females were more vulnerable to MFR than their mothers (FRG1) and grandmothers, which is consistent with the ‘predictive adaptive response’ hypothesis. Our findings reveal that MFR may induce intergenerational ovarian changes as an adaptive response to ensure reproductive success before death.


2010 ◽  
Vol 48 ◽  
pp. 275-287 ◽  
Author(s):  
Patrick O. McGowan ◽  
Moshe Szyf

An organism’s behavioural and physiological and social milieu influence and are influenced by the epigenome, which is comprised predominantly of chromatin and the covalent modification of DNA by methylation. Epigenetic patterns are sculpted during development to shape the diversity of gene expression programmes in the organism. In contrast with the genetic sequence, which is determined by inheritance and is virtually identical in all tissues, the epigenetic pattern varies from cell type to cell type and is potentially dynamic throughout life. It is postulated that different environmental exposures could effect epigenetic patterns relevant for human behaviour. Because epigenetic programming defines the state of expression of genes, epigenetic differences could have the same consequences as genetic polymorphisms. Yet in contrast with genetic sequence differences, epigenetic alterations are potentially reversible. In the present chapter, we will discuss evidence that epigenetic processes early in life play a role in defining inter-individual trajectories of behaviour, with implications for mental health in adulthood.


2006 ◽  
Vol 155 (suppl_1) ◽  
pp. S47-S50 ◽  
Author(s):  
P D Gluckman ◽  
M A Hanson

Disease occurs if an environmental challenge exceeds the ability of an individual to mount an effective adaptive response to it. Evolution has selected genomically determined traits, which are optimal for a species to survive the historical environment. However, this adaptive ability to withstand an environmental challenge varies among individuals and is itself a phenotypic characteristic: how is this determined? We argue that maternal and placental cues that constrain prenatal development, induce offspring to develop predictive adaptive responses more suited to a deprived postnatal environment, i.e. a more favorable phenotype for survival of the species than that which would be established by the genotype in the absence of environmental influence. This ‘survival phenotype’ can be exaggerated further by the postnatal environment. Since predictive adaptive responses maximize the chance of survival to reproduce, this phenomenon has itself been protected through evolution. Furthermore, such rapid adaptive responses may allow transgenerational transmission of phenotypic traits advantageous for survival of a species through transient environmental change. We argue that risk of disease is increased, when the actual postnatal environment does not match that predicted prenatally. In humans, this explains patterns of disease, especially those for which risk is determined in part during development, such as type 2 diabetes, cardiovascular disease and the rising risks of childhood obesity. The predictive adaptive response hypothesis extends foregoing concepts in this field and lends itself to experimental testing. It provides insights into ways to reduce the burden of certain common chronic diseases in both developed and developing countries.


2015 ◽  
Vol 6 (5) ◽  
pp. 399-406 ◽  
Author(s):  
K. M. Godfrey ◽  
P. M. Costello ◽  
K. A. Lillycrop

Evidence from both human and animal studies has shown that the prenatal and early postnatal environments influence susceptibility to chronic disease in later life and suggests that epigenetic processes are an important mechanism by which the environment alters long-term disease risk. Epigenetic processes, including DNA methylation, histone modification and non-coding RNAs, play a central role in regulating gene expression. The epigenome is highly sensitive to environmental factors in early life, such as nutrition, stress, endocrine disruption and pollution, and changes in the epigenome can induce long-term changes in gene expression and phenotype. In this review we focus on how the early life nutritional environment can alter the epigenome leading to an altered susceptibility to disease in later life.


2020 ◽  
Author(s):  
Matsapume Detcharoen ◽  
Martin P. Schilling ◽  
Wolfgang Arthofer ◽  
Birgit C. Schlick-Steiner ◽  
Florian M. Steiner

AbstractWolbachia, maternally inherited endosymbionts, infect nearly half of all arthropod species. Wolbachia manipulate their hosts to maximize their transmission, but they can also provide benefits such as nutrients and resistance to viruses for their hosts. The Wolbachia strain wMel was recently found to increase locomotor activities and possibly trigger cytoplasmic incompatibility in the fly Drosophila nigrosparsa. Here, we compared differential gene expression in Drosophila melanogaster (original host) and D. nigrosparsa (novel host), both uninfected and infected with wMel, using RNA sequencing to see if the two Drosophila species respond to the infection in the same or different ways. A total of 2164 orthologous genes were used. We found species-specific gene expression patterns. Significant changes shared by the fly species were confined to the expression of genes involved in heme binding and oxidation-reduction; the two host species differently changed the expression of genes when infected. Some of the genes were down-regulated in the infected D. nigrosparsa, which might indicate small positive effects of Wolbachia. We discuss our findings also in the light of how Wolbachia survive within both the native and the novel host.


Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 636 ◽  
Author(s):  
Yuling Dong ◽  
Hao Sun ◽  
Weichao Yang ◽  
Shuang Ma ◽  
Beibei Du ◽  
...  

Inulin is considered an efficient prebiotic and is beneficial for metabolic diseases via promoting intestinal probiotic enrichment and the metabolites of short-chain fatty acids (SCFAs). However, the effect of inulin on patients with InR deficiencies has seldom been reported. In this study, the lifespan, related gene expression, and gut microbiota of InRp5545/TM3 (insulin receptor mutant) Drosophila melanogaster under inulin treatment were investigated. The results showed that the lifespan was extended in only males and not in females. Furthermore, distinctly different patterns of gene expression were found between males and females, especially in the insulin/insulin-like growth factor (IGF)-like signalling (IIS) and target of rapamycin (TOR) pathways. Additionally, as a link between inulin and lifespan responses, the gut microbiota was distinctly separated by gender in both the standard diet group and the inulin treatment group, and the relationship between lifespan and the gut microbiota community was stronger in male flies than in females. This study provides preliminary evidence for the gender-dependent lifespan responses to inulin in insulin signalling-deficient Drosophila. However, controls such as wild-type and TM3 flies, and more InR mutant strains with different genetic backgrounds need to be further investigated to elucidate the mechanisms underlying the phenomenon.


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