High fat diet induces sex-specific differential gene expression in Drosophila melanogaster

Stobdan, Tsering; Sahoo, Debashis; Azad, Priti; Hartley, Iain; Heinrichsen, Erilynn; Zhou, Dan; Haddad, Gabriel G.

doi:10.1371/journal.pone.0213474

Cited by 35 publications

(54 citation statements)

References 75 publications

(79 reference statements)

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“…Our data agree, although males survived better on HFD than did genotype-matched mated females. Previous studies showed major transcriptome differences between males and mated females reared on HFD: females upregulated fatty acid metabolism and their stress response while males downregulated stress response genes (Heinrichsen et al 2014;Stobdan et al 2019). Our data suggests that Spen-KD flies maintain this sex-specific sensitivity to dietary fat intake.…”

Section: Discussionsupporting

confidence: 53%

Gene–Diet Interactions: Dietary Rescue of Metabolic Defects in spen-Depleted Drosophila melanogaster

et al. 2020

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Obesity and its comorbidities are a growing health epidemic. Interactions between genetic background, the environment, and behavior (i.e., diet) greatly influence organismal energy balance. Previously, we described obesogenic mutations in the gene Split ends (Spen) in Drosophila melanogaster, and roles for Spen in fat storage and metabolic state. Lipid catabolism is impaired in Spen-deficient fat storage cells, accompanied by a compensatory increase in glycolytic flux and protein catabolism. Here, we investigate gene–diet interactions to determine if diets supplemented with specific macronutrients can rescue metabolic dysfunction in Spen-depleted animals. We show that a high-yeast diet partially rescues adiposity and developmental defects. High sugar partially improves developmental timing as well as longevity of mated females. Gene–diet interactions were heavily influenced by developmental-stage-specific organismal needs: extra yeast provides benefits early in development (larval stages) but becomes detrimental in adulthood. High sugar confers benefits to Spen-depleted animals at both larval and adult stages, with the caveat of increased adiposity. A high-fat diet is detrimental according to all tested criteria, regardless of genotype. Whereas Spen depletion influenced phenotypic responses to supplemented diets, diet was the dominant factor in directing the whole-organism steady-state metabolome. Obesity is a complex disease of genetic, environmental, and behavioral inputs. Our results show that diet customization can ameliorate metabolic dysfunction underpinned by a genetic factor.

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Section: Discussionsupporting

confidence: 53%

Gene–Diet Interactions: Dietary Rescue of Metabolic Defects in spen-Depleted Drosophila melanogaster

et al. 2020

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“…and their stress response while males downregulated stress response genes 540 (Heinrichsen et al 2014;Stobdan et al 2019). Our data suggests that Spen-KD flies 541 maintain this sex-specific sensitivity to dietary fat intake.…”

Section: Discussion 391mentioning

confidence: 75%

Gene-diet interactions: dietary rescue of metabolic defects inspen-depleted Drosophila

Gillette

Hazegh

Nemkov

et al. 2019

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20Obesity and its co-morbidities are a growing health epidemic. Interactions between 21 genetic background and the environment and behavior (i.e. diet) greatly influence 22 organismal energy balance. Previously, we described obesogenic mutations in the 23 gene Split ends (Spen) in Drosophila melanogaster, and roles for Spen in fat storage 24 and metabolic state. In Spen-deficient storage cells lipid catabolism is impaired, 25 accompanied by a compensatory increase in glycolytic flux and protein catabolism. 26Here we investigate gene-diet interactions to determine if diets supplemented with 27 specific macronutrients can rescue metabolic dysfunction in Spen-depleted animals. We 28show that a high-yeast diet partially rescues adiposity and developmental defects. High 29 sugar partially improves developmental timing as well as adult longevity. Gene-diet 30 interactions were heavily influenced by developmental-stage-specific organismal needs: 31 extra yeast provides benefits early in development (larval stages) but becomes 32 detrimental in adulthood. High sugar confers benefits at both larval and adult stages, 33 with the caveat of increased adiposity. A high-fat diet is detrimental according to all 34 tested criteria, regardless of genotype. Whereas Spen depletion influenced phenotypic 35 responses to supplemented diets, diet was the dominant factor in directing the whole-36 organism steady-state metabolome. Obesity is a complex disease of genetic, 37 environmental, and behavioral inputs. Our results show that diet customization can 38 ameloriate metabolic dysfunction underpinned by a genetic factor. 39 utilization of nutrients (catabolism) to nutrient storage (anabolism). 50While diet can be a major driver of fat storage, gene-environment interactions 51 play a critical yet poorly understood role in the development of obesity and metabolic 52 syndrome, defined as "clustering of abdominal obesity, dyslipidemia, hyperglycemia and 53 hypertension" (Giovannucci 2007). Decades ago, the increased incidence of Diabetes 54Mellitus was attributed to an evolutionarily beneficial 'thrifty' genotype that is 55 incompatible with the modern Western Diet and lifestyle (Neel 1962). Evidence of 56 genetic adaptation to a diet high in polyunsaturated fatty acids can be found in the 57 genomes of Greenlandic Inuit, in the form of genetic variants in fatty acid desaturases 58 (Fumagalli et al. 2015;Chen et al. 2019). Accordingly, developing a comprehensive 59 understanding of obesity and metabolic syndrome demands examination of the interplay 60 between genetics and diet. 61Drosophila melanogaster is an excellent model in which to study gene function in 62 metabolism (Grönke et al. 2003(Grönke et al. , 2005Baker and Thummel 2007; Leopold and 63 Perrimon 2007;Schlegel and Stainier 2007;Guo et al. 2008;Beller et al. 2010; Reis et 64 al. 2010;Hazegh et al. 2017;Musselman and Kuhnlein 2018). Metabolic pathways are 65 highly conserved in Drosophila (Bernards and Hariharan 2001) and many fat regulatory 66 genes have functional orthol...

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“…In fruit flies, studies typically focus on whole-body or head tissue transcription (e.g. [75]); one or a few gene pathways known to affect diet responses at a time (e.g. [64]); one or two diet manipulations (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…[64]); one or two diet manipulations (e.g. [75][76][77]), but scarcely integrate over more than two organs and conditions at a time, or explore expression outside a few gene pathways. Further, despite costs trending downwards recently, sequencing of more highly replicated experiments remains unaffordable for many laboratories.…”

Section: Discussionmentioning

confidence: 99%

Diverse biological processes coordinate the transcriptional response to nutritional changes in a Drosophila melanogaster multiparent population

et al. 2020

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Background: Environmental variation in the amount of resources available to populations challenge individuals to optimize the allocation of those resources to key fitness functions. This coordination of resource allocation relative to resource availability is commonly attributed to key nutrient sensing gene pathways in laboratory model organisms, chiefly the insulin/TOR signaling pathway. However, the genetic basis of diet-induced variation in gene expression is less clear. Results: To describe the natural genetic variation underlying nutrient-dependent differences, we used an outbred panel derived from a multiparental population, the Drosophila Synthetic Population Resource. We analyzed RNA sequence data from multiple female tissue samples dissected from flies reared in three nutritional conditions: high sugar (HS), dietary restriction (DR), and control (C) diets. A large proportion of genes in the experiment (19.6% or 2471 genes) were significantly differentially expressed for the effect of diet, and 7.8% (978 genes) for the effect of the interaction between diet and tissue type (LRT, P adj. < 0.05). Interestingly, we observed similar patterns of gene expression relative to the C diet, in the DR and HS treated flies, a response likely reflecting diet component ratios. Hierarchical clustering identified 21 robust gene modules showing intra-modularly similar patterns of expression across diets, all of which were highly significant for diet or diet-tissue interaction effects (FDR P adj. < 0.05). Gene set enrichment analysis for different diet-tissue combinations revealed a diverse set of pathways and gene ontology (GO) terms (two-sample t-test, FDR < 0.05). GO analysis on individual co-expressed modules likewise showed a large number of terms encompassing many cellular and nuclear processes (Fisher exact test, P adj. < 0.01). Although a handful of genes in the IIS/TOR pathway including Ilp5, Rheb, and Sirt2 showed significant elevation in expression, many key genes such as InR, chico, most insulin peptide genes, and the nutrient-sensing pathways were not observed. Conclusions: Our results suggest that a more diverse network of pathways and gene networks mediate the diet response in our population. These results have important implications for future studies focusing on diet responses in natural populations.

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High fat diet induces sex-specific differential gene expression in Drosophila melanogaster

Cited by 35 publications

References 75 publications

Gene–Diet Interactions: Dietary Rescue of Metabolic Defects in spen-Depleted Drosophila melanogaster

Gene–Diet Interactions: Dietary Rescue of Metabolic Defects in spen-Depleted Drosophila melanogaster

Gene-diet interactions: dietary rescue of metabolic defects inspen-depleted Drosophila

Diverse biological processes coordinate the transcriptional response to nutritional changes in a Drosophila melanogaster multiparent population

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