Lucia Aronica

All Publications

• Changes in blood lipid concentrations associated with changes in intake of dietary saturated fat in the context of a healthy low-carbohydrate weight-loss diet: a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial. The American journal of clinical nutrition Shih, C. W., Hauser, M. E., Aronica, L., Rigdon, J., Gardner, C. D. 2019

  Abstract

  Background: For low-carbohydrate diets, a public health approach has focused on the replacement of carbohydrates with unsaturated fats. However, little research exists on the impacts of saturated fat intake on the lipid profile in the context of whole-food-based low-carbohydrate weight-loss diets.Objectives: The primary aim of this secondary analysis of the DIETFITS weight loss trial was to evaluate the associations between changes in percentage of dietary saturated fatty acid intake (%SFA) and changes in low-density lipoproteins, high-density lipoproteins, and triglyceride concentrations for those following a healthy low-carbohydrate (HLC) diet. The secondary aim was to examine these associations specifically for HLC dieters who had the highest 12-month increases in %SFA.Methods: In the DIETFITS trial, 609 generally healthy adults, aged 18-50 years, with body mass indices of 28-40 kg/m2 were randomly assigned to a healthy low-fat (HLF) or HLC diet for 12 months. In this analysis, linear regression, both without and with adjustment for potential confounders, was used to measure the association between 12-month change in %SFA and blood lipids in 208 HLC participants with complete diet and blood lipid data.Results: Participants consumed an average of 12-18% of calories from SFA. An increase of %SFA, without significant changes in absolute saturated fat intake, over 12 months was associated with a statistically significant decrease in triglycerides in the context of a weight-loss study in which participants simultaneously decreased carbohydrate intake. The association between increase in %SFA and decrease in triglycerides was no longer significant when adjusting for 12-month change in carbohydrate intake, suggesting carbohydrate intake may be a mediator of this relationship.Conclusions: Those on a low-carbohydrate weight-loss diet who increase their percentage intake of dietary saturated fat may improve their overall lipid profile provided they focus on a high-quality diet and lower their intakes of both calories and refined carbohydrates. This trial was registered at clinicaltrials.gov as NCT01826591.

  View details for PubMedID 30649213

• RW-2018-Research Workshop: The Effect of Nutrition on Epigenetic Status, Growth, and Health. JPEN. Journal of parenteral and enteral nutrition Skinner, M., Lumey, L. H., Fleming, T. P., Sapienza, C., Hoyo, C., Aronica, L., Thompson, J., Nichol, P. F. 2019

  Abstract

  The goal of the 2018 American Society for Parenteral and Enteral Nutrition (ASPEN) Research Workshop was to explore the influence of nutrition and dietary exposure to xenobiotics on the epigenome during critical periods in development and how these exposures influence both disease incidence and severity transgenerationally. A growing compendium of research indicates that the incidence and severity of common and costly human diseases may be influenced by dietary exposures and deficiencies that modify the epigenome. The greatest periods of vulnerability to these exposures are the periconception period and early childhood. Xenobiotics in the food chain, protein malnutrition, and methyl donor deficiencies could have a profound bearing on the risk of developing heart disease, diabetes, obesity, hypertension, and mental illness over multiple generations. The financial impact and the life burden of these diseases are enormous. These and other aspects of nutrition, epigenetics, and health are explored in this research workshop.

  View details for PubMedID 30997688

• A systematic review of studies of DNA methylation in the context of a weight loss intervention EPIGENOMICS Aronica, L., Levine, A. J., Brennan, K., Mi, J., Gardner, C., Haile, R. W., Hitchins, M. P. 2017; 9 (5): 769-787

  Abstract

  Obesity results from the interaction of genetic and environmental factors, which may involve epigenetic mechanisms such as DNA methylation (DNAm).We have followed the PRISMA protocol to select studies that analyzed DNAm at baseline and end point of a weight loss intervention using either candidate-locus or genome-wide approaches.Six genes displayed weight loss associated DNAm across four out of nine genome-wide studies. Weight loss is associated with significant but small changes in DNAm across the genome, and weight loss outcome is associated with individual differences in baseline DNAm at several genomic locations.The identified weight loss associated DNAm markers, especially those showing reproducibility across different studies, warrant validation by further studies with robust design and adequate power.

  View details for DOI 10.2217/epi-2016-0182

  View details for Web of Science ID 000401642200014

  View details for PubMedID 28517981

• A systematic review of studies of DNA methylation in the context of a weight loss intervention Epigenomics Aronica, L., et al 2017

  View details for DOI 10.2217/epi-2016-0182

• The spliceosome-associated protein Nrl1 suppresses homologous recombination-dependent R-loop formation in fission yeast. Nucleic acids research Aronica, L., Kasparek, T., Ruchman, D., Marquez, Y., Cipak, L., Cipakova, I., Anrather, D., Mikolaskova, B., Radtke, M., Sarkar, S., Pai, C., Blaikley, E., Walker, C., Shen, K., Schroeder, R., Barta, A., Forsburg, S. L., Humphrey, T. C. 2016; 44 (4): 1703-1717

  Abstract

  The formation of RNA-DNA hybrids, referred to as R-loops, can promote genome instability and cancer development. Yet the mechanisms by which R-loops compromise genome instability are poorly understood. Here, we establish roles for the evolutionarily conserved Nrl1 protein in pre-mRNA splicing regulation, R-loop suppression and in maintaining genome stability. nrl1Δ mutants exhibit endogenous DNA damage, are sensitive to exogenous DNA damage, and have defects in homologous recombination (HR) repair. Concomitantly, nrl1Δ cells display significant changes in gene expression, similar to those induced by DNA damage in wild-type cells. Further, we find that nrl1Δ cells accumulate high levels of R-loops, which co-localize with HR repair factors and require Rad51 and Rad52 for their formation. Together, our findings support a model in which R-loop accumulation and subsequent DNA damage sequesters HR factors, thereby compromising HR repair at endogenously or exogenously induced DNA damage sites, leading to genome instability.

  View details for DOI 10.1093/nar/gkv1473

  View details for PubMedID 26682798

  View details for PubMedCentralID PMC4770224

• A Tetrahymena Hsp90 co-chaperone promotes siRNA loading by ATP-dependent and ATP-independent mechanisms EMBO JOURNAL Woehrer, S. L., Aronica, L., Suhren, J. H., Busch, C. J., Noto, T., Mochizuki, K. 2015; 34 (4): 559-577

  Abstract

  The loading of small interfering RNAs (siRNAs) and microRNAs into Argonaute proteins is enhanced by Hsp90 and ATP in diverse eukaryotes. However, whether this loading also occurs independently of Hsp90 and ATP remains unclear. We show that the Tetrahymena Hsp90 co-chaperone Coi12p promotes siRNA loading into the Argonaute protein Twi1p in both ATP-dependent and ATP-independent manners in vitro. The ATP-dependent activity requires Hsp90 and the tetratricopeptide repeat (TPR) domain of Coi12p, whereas these factors are dispensable for the ATP-independent activity. Both activities facilitate siRNA loading by counteracting the Twi1p-binding protein Giw1p, which is important to specifically sort the 26- to 32-nt siRNAs to Twi1p. Although Coi12p lacking its TPR domain does not bind to Hsp90, it can partially restore the siRNA loading and DNA elimination defects of COI12 knockout cells, suggesting that Hsp90- and ATP-independent loading of siRNA occurs in vivo and plays a physiological role in Tetrahymena.

  View details for DOI 10.15252/embj.201490062

  View details for Web of Science ID 000349695100012

  View details for PubMedID 25588944

• How Healthy Eating Could Starve Out Cancer Aronica, L. Europe PubMed Central. 2014

  Abstract

  Europe PubMed Central People's Choice Award

• The Tetrahymena Argonaute-Binding Protein Giw1p Directs a Mature Argonaute-siRNA Complex to the Nucleus CELL Noto, T., Kurth, H. M., Kataoka, K., Aronica, L., DeSouza, L. V., Siu, K. W., Pearlman, R. E., Gorovsky, M. A., Mochizuki, K. 2010; 140 (5): 692-703

  Abstract

  Emerging evidence suggests that RNA interference (RNAi)-related processes act both in the cytoplasm and in the nucleus. However, the process by which the RNAi machinery is transported into the nucleus remains poorly understood. The Tetrahymena Argonaute protein Twi1p localizes to the nucleus and is crucial for small RNA-directed programmed DNA elimination. In this study, we identify Giw1p, which binds to Twi1p and is required for its nuclear localization. Furthermore, the endoribonuclease (Slicer) activity of Twi1p plays a vital role in the removal of one of the two strands of Twi1p-associated small interfering RNAs (siRNAs), leading to a functionally mature Twi1p-siRNA complex. Slicer activity is also shown to be required for nuclear localization of Twi1p and for its association with Giw1p. These results suggest that Giw1p senses the state of Twi1p-associated siRNAs and selectively transports the mature Twi1p-siRNA complex into the nucleus.

  View details for DOI 10.1016/j.cell.2010.02.010

  View details for Web of Science ID 000275197400018

  View details for PubMedID 20211138

• Study of an RNA helicase implicates small RNA-noncoding RNA interactions in programmed DNA elimination in Tetrahymena GENES & DEVELOPMENT Aronica, L., Bednenko, J., Noto, T., DeSouza, L. V., Siu, K. W., Loidl, J., Pearlman, R. E., Gorovsky, M. A., Mochizuki, K. 2008; 22 (16): 2228-2241

  Abstract

  Tetrahymena eliminates micronuclear-limited sequences from the developing macronucleus during sexual reproduction. Homology between the sequences to be eliminated and approximately 28-nucleotide small RNAs (scnRNAs) associated with an Argonaute family protein Twi1p likely underlies this elimination process. However, the mechanism by which Twi1p-scnRNA complexes identify micronuclear-limited sequences is not well understood. We show that a Twi1p-associated putative RNA helicase Ema1p is required for the interaction between Twi1p and chromatin. This requirement explains the phenotypes of EMA1 KO strains, including loss of selective down-regulation of scnRNAs homologous to macronuclear-destined sequences, loss of H3K9 and K27 methylation in the developing new macronucleus, and failure to eliminate DNA. We further demonstrate that Twi1p interacts with noncoding transcripts derived from parental and developing macronuclei and this interaction is greatly reduced in the absence of Ema1p. We propose that Ema1p functions in DNA elimination by stimulating base-pairing interactions between scnRNAs and noncoding transcripts in both parental and developing new macronuclei.

  View details for DOI 10.1101/gad.481908

  View details for Web of Science ID 000258486800009

  View details for PubMedID 18708581