CIRCUMSTANCES AFFECTING THE NUTRITIONAL REQUIREMENTS OF <i>DROSOPHILA MELANOGASTER</i>

Sang, James H.

doi:10.1111/j.1749-6632.1959.tb36911.x

Cited by 86 publications

(50 citation statements)

References 18 publications

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“…S5). This amount is identical to the optimal amount required for Drosophila larval survival on a minimal defined medium (Sang 1956). A number of other sterols are able to substitute for cholesterol in these experiments, including 7-dehydrocholesterol, ergosterol, dehydroergosterol, sitosterol, and stigmasterol (data not shown), consistent with their ability to support normal growth of wild-type Drosophila (Cooke and Sang 1970).…”

Section: Dhr96 Regulates the Transcriptional Response To Cholesterolsupporting

confidence: 62%

The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

Horner¹,

Pardee²,

et al. 2009

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Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-cholesterol diet. The cholesterol accumulation phenotype can be attributed to misregulation of npc1b, an ortholog of the mammalian Niemann-Pick C1-like 1 gene NPC1L1, which is essential for dietary cholesterol uptake. These studies define DHR96 as a central regulator of cholesterol homeostasis. Cholesterol is an essential component of cell membranes that influences the permeability and fluidity of the lipid bilayer. Cholesterol also acts as a precursor for steroid hormone biosynthesis and contributes to cell-cell signaling pathways. These critical cellular functions are supported by regulatory mechanisms that maintain normal cholesterol levels and prevent hypercholesterolemia, which is a major risk factor for cardiovascular disease in humans. Cholesterol homeostasis in vertebrates is achieved primarily through de novo synthesis and dietary uptake (Ikonen 2008). Although extensive studies have defined a central role for the sterol regulatory elementbinding protein (SREBP) family of transcription factors in controlling cholesterol synthesis (Brown and Goldstein 1997), the mechanisms that regulate dietary cholesterol absorption remain more poorly understood. One central component of this pathway is the Niemann-Pick C1-like 1 gene NPC1L1, which encodes a plasma membrane protein that mediates the uptake of dietary cholesterol by the intestine (Wang 2007;Ge et al. 2008). Mouse mutants for NPC1L1 display significantly reduced levels of cholesterol absorption and are insensitive to treatment with the anti-hypercholesterolemia drug ezetimibe, which acts as a specific NPC1L1 inhibitor (Davis et al. 2008). Another major regulator of cholesterol homeostasis is the liver X receptor a (LXRa) nuclear receptor, which binds cholesterol metabolites and regulates the transcription of genes that control cholesterol transport and metabolism, including NPC1L1 (Duval et al. 2006;Kalaany and Mangelsdorf 2006;Valasek et al. 2007).We used the fruit fly, Drosophila, as a model system to study the regulation of cholesterol homeostasis. Unlike vertebrates, insects are cholesterol auxotrophs that are unable to synthesize this essential compound (Va'nt Hoog 1936). Little is known, however, about the mechanisms that regulate the uptake of dietary cholesterol in Drosophila. A recent study showed that the fly ortholog of NPC1L1, npc1b, is expressed specifically in the midgut and is essential for dietary cholesterol absorption (Voght et al. 2007). Other NPC disease gene homologs in Drosophila also contribute to cholesterol homeostasis. The Drosophila ortholog of vert...

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Section: Dhr96 Regulates the Transcriptional Response To Cholesterolsupporting

confidence: 62%

The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

Horner¹,

Pardee²,

et al. 2009

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“…Amino acid concentrations in a 15% yeast sugar diet were determined by HPLC at the Nutritional & Environmental Analytical Services Laboratory at Cornell University (Ithaca, NY), except for methionine and tryptophan, which could not be Hinton et al (1951). Since the specific vitamin, mineral and other nutrient intakes that are required for maximal longevity in adult Drosophila are largely unknown, we derived the medium nutrient concentrations from requirements for optimal larval development for those nutrients for which data are available (Villee and Bissell 1948;Hinton et al 1951;Sang 1955). Where nutrient requirements are uncertain, amounts in the defined medium correspond to the theoretical content of the 15% yeast-sugar reference diet.…”

Section: Dietsmentioning

confidence: 99%

Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet

Troen

French

Roberts

et al. 2006

AGE

108

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Experimentally restricting dietary calories, while maintaining adequate dietary nutrient content, extends lifespan in phylogenetically diverse species; thus suggesting the existence of conserved pathways which can modify lifespan in response to energy intake. However, in some cases the impact on longevity may depend on the quality of the energy source. In Drosophila, restriction of dietary yeast yields considerable lifespan extension whereas isocaloric restriction of dietary sugar yields only modest extension, indicating that other diet-responsive pathways can modify lifespan in this species. In rodents, restricting intake of a single amino acid -methionine -extends lifespan. Here we show that dietary methionine can modify lifespan in adult female, non-virgin Oregon-R strain Drosophila fed a chemically defined media. Compared to a diet containing 0.135% methionine and 15% glucose, high dietary methionine (0.405%) shortened maximum lifespan by 2.33% from 86 to 84 days and mean lifespan by 9.55% from 71.7 to 64.9 days. Further restriction of methionine to 0.045% did not extend maximum lifespan and shortened mean lifespan by 1.95% from 71.1 to 70.3 days. Restricting glucose from 15% to 5% while holding methionine at a concentration of 0.135%, modestly extended maximum lifespan by 5.8% from 86 to 91 days, without extending mean lifespan. All these diet-induced changes were highly significant (log-rank p<0.0001). Notably, all four diets resulted in considerably longer life spans than those typically reported for flies fed conventional yeast and sugar based diets. Such defined diets can be used to identify lifespan-modifying pathways and specific gene-nutrient interactions in Drosophila.

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“…In contrast to the studies claiming that A. egypti and D. melanogaster can synthesize folic acid, other studies have shown these insects need the vitamin in the diet to develop at normal rates and to pupate. 12,20,21 Perhaps the results of these studies have differed due to differences in the microbial content of the insects. In the Sang study that supported de novo synthesis of folate, the fruit flies were "axenically"-reared (free of contaminating organisms) from sterilized and dechorionated eggs, though effectiveness of the latter procedure was not discussed.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15][16] Furthermore, it is ReseaRch papeR ReseaRch papeR determined sufficient amount of 3.0 μg/ml. 12 Despite the 600-fold range in dietary folate level, whole-body folate levels of first generation larvae were not significantly affected (Fig. 1B).…”

Section: Introductionmentioning

confidence: 99%

“…10 In addition, there have been claims that a few insects can synthesize folic acid: the mosquito Aedes aegypti and the fruit flies Drosophila virilis and D. melanogaster. 11,12 The evidence for folate synthesis by these insects was the observation that D. melanogaster larvae can survive to the third instar stage without dietary folic acid, and that D. virilis and A. egypti larvae reared without dietary folic acid contained manyfold higher folate levels than eggs.…”

Section: Introductionmentioning

confidence: 99%

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Effects of dietary folic acid level and symbiotic folate production on fitness and development in the fruit flyDrosophilamelanogaster

Blatch

Meyer

Harrison

2010

Fly

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CIRCUMSTANCES AFFECTING THE NUTRITIONAL REQUIREMENTS OF DROSOPHILA MELANOGASTER

Cited by 86 publications

References 18 publications

The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet

Effects of dietary folic acid level and symbiotic folate production on fitness and development in the fruit flyDrosophilamelanogaster

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