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Feeding with a ketonic diet confers complete protection against malaria

ABSTRACT: Feeding with a ketonic diet confers complete protection against malaria

PROVIDER: PRJNA1145259 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30161086_1.fastq.gz	Fastqsanger.gz
	SRR30161086_2.fastq.gz	Fastqsanger.gz
	SRR30161087_1.fastq.gz	Fastqsanger.gz
	SRR30161087_2.fastq.gz	Fastqsanger.gz
	SRR30161088_1.fastq.gz	Fastqsanger.gz

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Feeding with a ketonic diet confers complete protection against malaria

Project description:Environmental factors restrict malarial parasite development, but the influence of host metabolic variations on the infectivity of blood-stage parasite is not fully understood. Here, we show that the administration of a ketogenic diet (KD) to mice conferred complete protection against Plasmodim berghei infection. The β-hydroxybutyrate (βOHB), a predominant ketone body, was elevated in P. berghei infected mice on a KD, and inhibited the proliferation of both P. berghei and P. falciparum. A KD and βOHB induced metabolic reprogramming in the parasites resulting in reduced cellular nicotinamide adenine dinucleotide (NAD), which led to the downregulation of genes controlling parasite development, erythrocyte invasion and pathogenicity. This study reveal that A KD-derived βOHB can ultimately cause the developmental arrest of Plasmodium parasites and benefits host resistance to malaria.

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Molecular Hallmarks of Naturally Acquired Immunity to Malaria

Project description:Immunity to malaria can be acquired through natural exposure to Plasmodium falciparum (Pf), but only after years of repeated infections. Typically, this immunity is acquired by adolescence and confers protection against disease, but not Pf infection per se. Efforts to understand the mechanisms of this immunity are integral to the development of a vaccine that would mimic the induction of adult immunity in children. The current study applies transcriptomic analyses to a cohort from the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal. Signatures that correlate with protection from malaria may yield new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural Pf infection. The resulting datasets will be of considerable value in the urgent worldwide effort to develop a malaria vaccine that could prevent more than a million deaths annually. 108 samples; paired pre- and post-challenge for 54 individuals 198 samples; paired pre- and post-challenge for 99 individuals

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Molecular Hallmarks of Naturally Acquired Immunity to Malaria

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Plasmodium berghei ANKA

Project description:Feeding with a ketonic diet confers complete protection against malaria

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G6PC2 confers protection against hypoglycemia upon ketogenic diet feeding and prolonged fasting.

Project description:ObjectiveG6PC2 is predominantly expressed in pancreatic islet beta cells. G6PC2 hydrolyzes glucose-6-phosphate to glucose and inorganic phosphate, thereby creating a futile substrate cycle that opposes the action of glucokinase. This substrate cycle determines the sensitivity of glucose-stimulated insulin secretion to glucose and hence regulates fasting blood glucose (FBG) but not fasting plasma insulin (FPI) levels. Our objective was to explore the physiological benefit this cycle confers.MethodsWe investigated the response of wild type (WT) and G6pc2 knockout (KO) mice to changes in nutrition.ResultsPancreatic G6pc2 expression was little changed by ketogenic diet feeding but was inhibited by 24 hr fasting and strongly induced by high fat feeding. When challenged with either a ketogenic diet or 24 hr fasting, blood glucose fell to 70 mg/dl or less in G6pc2 KO but not WT mice, suggesting that G6PC2 may have evolved, in part, to prevent hypoglycemia. Prolonged ketogenic diet feeding reduced the effect of G6pc2 deletion on FBG. The hyperglycemia associated with high fat feeding was partially blunted in G6pc2 KO mice, suggesting that under these conditions the presence of G6PC2 is detrimental. As expected, FPI changed but did not differ between WT and KO mice in response to fasting, ketogenic and high fat feeding.ConclusionsSince elevated FBG levels are associated with increased risk for cardiovascular-associated mortality (CAM), these studies suggest that, while G6PC2 inhibitors would be useful for lowering FBG and the risk of CAM, partial inhibition will be important to avoid the risk of hypoglycemia.

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The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation

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GTP Cyclohydrolase I Confers Metabolic Protection Against Lipid Peroxidation in Glioblastoma

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