title: In vivo high-resolution magic angle spinning magnetic resonance spectroscopy of Drosophila melanogaster at 14.1 T shows trauma in aging and in innate immune-deficiency is linked to reduced insulin signaling.
abstract: In vivo magnetic resonance spectroscopy (MRS), a non-destructive biochemical tool for investigating live organisms, has yet to be used in the fruit fly Drosophila melanogaster, a useful model organism for investigating genetics and physiology. We developed and implemented a high-resolution magic-angle-spinning (HRMAS) MRS method to investigate live Drosophila at 14.1 T. We demonstrated, for the first time, the feasibility of using HRMAS MRS for molecular characterization of Drosophila with a conventional MR spectrometer equipped with an HRMAS probe. We showed that the metabolic HRMAS MRS profiles of injured, aged wild-type (wt) flies and of immune deficient (imd) flies were more similar to chico flies mutated at the chico gene in the insulin signaling pathway, which is analogous to insulin receptor substrate1-4 (IRS1-4) in mammals and less to those of adipokinetic hormone receptor (akhr) mutant flies, which have an obese phenotype. We thus provide evidence for the hypothesis that trauma in aging and in innate immune-deficiency is linked to insulin signaling. This link may explain the mitochondrial dysfunction that accompanies insulin resistance and muscle wasting that occurs in trauma, aging and immune system deficiencies, leading to higher susceptibility to infection. Our approach advances the development of novel in vivo non-destructive research approaches in Drosophila, suggests biomarkers for investigation of biomedical paradigms, and thus may contribute to novel therapeutic development.
authors.affiliation: NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burn Institute, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Righi
authors.forename: Yiorgos
authors.initials: Y
authors.lastname: Apidianakis
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Mintzopoulos
authors.forename: Loukas
authors.initials: L
authors.lastname: Astrakas
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Rahme
authors.forename: A Aria
authors.initials: AA
authors.lastname: Tzika
mesh_terms: D000367:Age Factors; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000378:metabolism*; D007153:Immunologic Deficiency Syndromes; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D018027:Receptors, Glucagon / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: C533337:AKHR protein, Drosophila; D000596:Amino Acids; D029721:Drosophila Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D018027:Receptors, Glucagon; C120233:chico protein, Drosophila; C439909:imd protein, Drosophila