A Drosophila Model of High Sugar Diet-Induced Cardiomyopathy

Na, Jianbo; Musselman, Laura Palanker; Pendse, Jay; Baranski, Thomas J.; Bodmer, Rolf; Ocorr, Karen; Cagan, Ross L.

doi:10.1371/journal.pgen.1003175

Cited by 219 publications

(254 citation statements)

References 69 publications

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“…The axenic flies displayed hyperlipidemia and hyperglycemia, as is found in conventional Drosophila only on diets of exceptionally high carbohydrate content (Musselman et al, 2011;Na et al, 2013). This effect was particularly pronounced in axenic flies of low body mass, which occurred on diets of low yeast content.…”

Section: Research Articlementioning

confidence: 73%

Gut microbiota dictates the metabolic response ofDrosophilato diet

Wong

Dobson

Douglas

2014

Journal of Experimental Biology

266

261

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Animal nutrition is profoundly influenced by the gut microbiota, but knowledge of the scope and core mechanisms of the underlying animal-microbiota interactions is fragmentary. To investigate the nutritional traits shaped by the gut microbiota of Drosophila, we determined the microbiota-dependent response of multiple metabolic and performance indices to systematically varied diet composition. Diet-dependent differences between Drosophila bearing its unmanipulated microbiota (conventional flies) and experimentally deprived of its microbiota (axenic flies) revealed evidence for: microbial sparing of dietary B vitamins, especially riboflavin, on lowyeast diets; microbial promotion of protein nutrition, particularly in females; and microbiota-mediated suppression of lipid/carbohydrate storage, especially on high sugar diets. The microbiota also sets the relationship between energy storage and body mass, indicative of microbial modulation of the host signaling networks that coordinate metabolism with body size. This analysis identifies the multiple impacts of the microbiota on the metabolism of Drosophila, and demonstrates that the significance of these different interactions varies with diet composition and host sex.

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Section: Research Articlementioning

confidence: 73%

Gut microbiota dictates the metabolic response ofDrosophilato diet

Wong

Dobson

Douglas

2014

Journal of Experimental Biology

266

261

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“…Obese Drosophila exhibited increased cardiac steatosis and fibrosis compared with control flies, supporting an analogous burden to the insect and human hearts (Birse et al, 2010;Diop et al, 2015;Hardy et al, 2015;Na et al, 2013). Heart failure rate is highest in obese flies fed high-calorie diets and lowest in lean low-calorie-fed flies (Bazzell et al, 2013).…”

Section: The Heartmentioning

confidence: 76%

“…Some investigators have recently begun using an obesogenic high-sugar, high-fat diet in Drosophila obesity studies that is similar to that used in many rodent studies and is probably closest to the typical 'Western' obesogenic diet (G. Melkani, personal communication). Diet-induced obesity in flies is associated with many of the pathophysiological consequences found in humans, including hyperglycemia, insulin resistance, cardiac arrhythmia and fibrosis, reduced longevity (Birse et al, 2010;Na et al, 2013) and nephrosis . One can also assess the ability to survive on and process high-calorie obesogenic diets, or the degree of 'obesity tolerance'.…”

Section: Diet-induced Obesity In Drosophilamentioning

confidence: 99%

Drosophilaas a model to study obesity and metabolic disease

Musselman

Kühnlein

2018

Journal of Experimental Biology

Self Cite

181

130

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Excess adipose fat accumulation, or obesity, is a growing problem worldwide in terms of both the rate of incidence and the severity of obesity-associated metabolic disease. Adipose tissue evolved in animals as a specialized dynamic lipid storage depot: adipose cells synthesize fat (a process called lipogenesis) when energy is plentiful and mobilize stored fat (a process called lipolysis) when energy is needed. When a disruption of lipid homeostasis favors increased fat synthesis and storage with little turnover owing to genetic predisposition, overnutrition or sedentary living, complications such as diabetes and cardiovascular disease are more likely to arise. The vinegar fly Drosophila melanogaster (Diptera: Drosophilidae) is used as a model to better understand the mechanisms governing fat metabolism and distribution. Flies offer a wealth of paradigms with which to study the regulation and physiological effects of fat accumulation. Obese flies accumulate triacylglycerols in the fat body, an organ similar to mammalian adipose tissue, which specializes in lipid storage and catabolism. Discoveries in Drosophila have ranged from endocrine hormones that control obesity to subcellular mechanisms that regulate lipogenesis and lipolysis, many of which are evolutionarily conserved. Furthermore, obese flies exhibit pathophysiological complications, including hyperglycemia, reduced longevity and cardiovascular functionsimilar to those observed in obese humans. Here, we review some of the salient features of the fly that enable researchers to study the contributions of feeding, absorption, distribution and the metabolism of lipids to systemic physiology.

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“…The concentration of sucrose used for the high-sugar diet (450 mM) was three times the typical amount used in the base diet (150 mM), but below the concentration used in chronic high-sugar diets designed to induce insulin resistance and diabetic phenotypes in flies (1 M) (Baker and Thummel 2007;Musselman et al 2011;Na et al 2013). For each toxin, the amount used in the mixture (BPA, high sugar, and DEHP combined) was identical to that used in the single exposures.…”

Section: Resultsmentioning

confidence: 99%

High Intake of Dietary Sugar Enhances Bisphenol A (BPA) Disruption and Reveals Ribosome-Mediated Pathways of Toxicity

Branco¹,

Lemos²

2014

Genetics

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Bisphenol A (BPA) is an organic compound to which human populations are ubiquitously exposed. Epidemiological data suggest BPA exposure might be associated with higher rates of diabetes and reproductive anomalies. Health concerns also include transgenerational consequences, but these mechanisms are crudely defined. Similarly, little is known about synergistic interactions between BPA and other substances. Here we show that acute and chronic exposure to BPA causes genome-wide modulation of several functionally coherent genetic pathways in the fruit fly Drosophila melanogaster. In particular, BPA exposure causes massive downregulation of testis-specific genes and upregulation of ribosome-associated genes widely expressed across tissues. In addition, it causes the modulation of transposable elements that are specific to the ribosomal DNA loci, suggesting that nucleolar stress might contribute to BPA toxicity. The upregulation of ribosome-associated genes and the impairment of testis-specific gene expression are significantly enhanced upon BPA exposure with a high-sugar diet. Our results suggest that BPA and dietary sugar might functionally interact, with consequences to regulatory programs in both reproductive and somatic tissues. E XPOSURE to environmental toxins is widespread. It is well documented, for instance, that human populations are commonly exposed to bisphenol A (BPA), bis(2-ethylhexyl) phthalate (DEHP), dioxins, and other organic molecules produced at industrial scales. Toxins might act by modulating epigenetic pathways to change the expression of genes and normal cellular homeostasis and could result in transgenerational consequences. The fast pace at which new compounds are invented and become ubiquitous in the environment poses a challenge to safety assessment. This challenge emerges not only from the large number of compounds to evaluate, but also from the high dimensionality of toxic responses across tissue types and developmental stages. This is further aggravated by the potential for unexpected synergism among toxins in mixtures. Sensitivity might also be strongly dependent on the specific epigenomic features and genetic makeup of an individual (Du et al. 2004).Genomic analyses have uncovered levels of human genetic variation not surmised a few decades ago (e.g., Sudmant et al. 2010). Cost-effective epigenetic and physiological models are needed for (i) addressing tissue-specific responses to toxins, (ii) gaining insights into mechanisms of epigenetic toxicity, and (iii) evaluating the manifestation of these responses across naturally occurring genotypes. In particular, cost-effective models with massive publicly available genetic information (Zwarts et al. 2011; King et al. 2012a,b;Mackay et al. 2012) might allow for genome-wide evaluation of toxic responses and assessment of coexposure outcomes in conjunction with the evaluation of unique individual responses.BPA is one of the most abundantly produced chemicals worldwide, reaching an annual volume .4 million tons (Burridge 2003). Multi...

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A Drosophila Model of High Sugar Diet-Induced Cardiomyopathy

Cited by 219 publications

References 69 publications

Gut microbiota dictates the metabolic response ofDrosophilato diet

Gut microbiota dictates the metabolic response ofDrosophilato diet

Drosophilaas a model to study obesity and metabolic disease

High Intake of Dietary Sugar Enhances Bisphenol A (BPA) Disruption and Reveals Ribosome-Mediated Pathways of Toxicity

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