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Biomedical subjects

Michael J Pankratz

Publications and source records attributed to Michael J Pankratz.

7 recordsLinked to original sources
PubMed2006

Purine and folate metabolism as a potential target of sex-specific nutrient allocation in Drosophila and its implication for lifespan-reproduction tradeoff.

The reallocation of metabolic resources is important for survival during periods of limited nutrient intake. This has an influence on diverse physiological processes, including reproduction, repair, and aging. One important aspect of resource allocation is the difference between males and females in response to nutrient stress. We identified several groups of genes that are regulated in a sex-biased manner under complete or protein starvation. These range from expected differences in genes involved in reproductive physiology to those involved in amino acid utilization, sensory perception, immune response, and growth control. A striking difference was observed in purine and the tightly interconnected folate metabolism upon protein starvation. From these results, we conclude that the purine and folate metabolic pathway is a major point of transcriptional regulation during resource allocation and may have relevance for understanding the physiological basis for the observed tradeoff between reproduction and longevity.

Adaptation, Physiological↗
PubMed2005

Candidate gustatory interneurons modulating feeding behavior in the Drosophila brain.

Feeding is a fundamental activity of all animals that can be regulated by internal energy status or external sensory signals. We have characterized a zinc finger transcription factor, klumpfuss (klu), which is required for food intake in Drosophila larvae. Microarray analysis indicates that expression of the neuropeptide gene hugin (hug) in the brain is altered in klu mutants and that hug itself is regulated by food signals. Neuroanatomical analysis demonstrates that hug-expressing neurons project axons to the pharyngeal muscles, to the central neuroendocrine organ, and to the higher brain centers, whereas hug dendrites are innervated by external gustatory receptor-expressing neurons, as well as by internal pharyngeal chemosensory organs. The use of tetanus toxin to block synaptic transmission of hug neurons results in alteration of food intake initiation, which is dependent on previous nutrient condition. Our results provide evidence that hug neurons function within a neural circuit that modulates taste-mediated feeding behavior.

Animals↗
PubMed2004

Starvation response in mouse liver shows strong correlation with life-span-prolonging processes.

We have monitored global changes in gene expression in mouse liver in response to fasting and sugar-fed conditions using high-density microarrays. From approximately 20,000 different genes, the significantly regulated ones were grouped into specific signaling and metabolic pathways. Striking changes in lipid signaling cascade, insulin and dehydroepiandrosterone (DHEA) hormonal pathways, urea cycle and S-adenosylmethionine-based methyl transfer systems, and cell apoptosis regulators were observed. Since these pathways have been implicated to play a role in the aging process, and since we observe significant overlap of genes regulated upon starvation with those regulated upon caloric restriction, our analysis suggests that starvation may elicit a stress response that is also elicited during caloric restriction. Therefore, many of the signaling and metabolic components regulated during fasting may be the same as those which mediate caloric restriction-dependent life-span extension.

ATP-Binding Cassette Transporters↗
PubMed2004

Linking nutrition to genomics.

The new scientific field of nutrigenomics utilizes genomic tools, like microarrays, to analyze metabolic adaptations induced by variations in nutritional status. Here we describe how transcriptional regulation patterns caused by nutritional changes can be identified using gene expression profiling. This includes technical remarks on microarray analysis and data processing, as well as giving biological meaning to statistically solid data. We highlight our recent findings of transcriptional regulation of genes representing specific signaling and metabolic pathways in mouse liver under starvation. The results show strong correlations to previously identified responses to caloric restriction, which can be linked to lifespan extension.

Amino Acids↗
PubMed2002

Nutrient control of gene expression in Drosophila: microarray analysis of starvation and sugar-dependent response.

We have identified genes regulated by starvation and sugar signals in Drosophila larvae using whole-genome microarrays. Based on expression profiles in the two nutrient conditions, they were organized into different categories that reflect distinct physiological pathways mediating sugar and fat metabolism, and cell growth. In the category of genes regulated in sugar-fed, but not in starved, animals, there is an upregulation of genes encoding key enzymes of the fat biosynthesis pathway and a downregulation of genes encoding lipases. The highest and earliest activated gene upon sugar ingestion is sugarbabe, a zinc finger protein that is induced in the gut and the fat body. Identification of potential targets using microarrays suggests that sugarbabe functions to repress genes involved in dietary fat breakdown and absorption. The current analysis provides a basis for studying the genetic mechanisms underlying nutrient signalling.

Animal Feed↗