Physiological effects and transgenerational inheritance induced by cholesterol-rich diet in Caenorhabditis elegans

• Grant number: 17/22057-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2018
• End date: August 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Willian Goulart Salgueiro
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics, AP.TEM
• Associated scholarship(s): 19/14391-8 - Screening and characterization of Dicer regulators in C. elegans, BE.EP.MS

Abstract

Cholesterol is an essential precursor for many physiological processes, mainly by giving rise to a big array of endocrine signals. However, the excessive intake of a lipid and cholesterol rich occidental diet may lead to obesity and dyslipidemia, what in turn increase the risk for metabolic and cardiovasculardiseases. Besides that, there is a growing amount of evidence which suggests that many metabolic diseases, including obesity and dyslipidemia, may be transgenerationally inherited. Such possibility is alarming, once it might allow the perpetration of their effects for generations. Considering that basic research may be limited by time and money consuming activities concerning mammals handling, the nematode C. elegans arises as an amenable alternative. This invertebrate has relatively conserved metabolic pathways regarding fatty acids synthesis, storage and mobilization. These same pathways are known for being responsive to cholesterol derivatives. Importantly, C. elegans do not synthesize cholesterol, thus its levels can be controlled through diet. Also, its short lifespan and generation time render C. elegans the ability to be employed in transgenerational studies. Not published data of our laboratory shows that C. elegans P0 parental generation supplemented with high cholesterol levels gives birth to F1 and F2 filial generations, cultivated under regular dietary conditions, which have altered lifespan. Thus, this proposal has as its main objective to understand how high cholesterol levels alter C. elegans physiology, and also to elucidate the mechanisms by which these alterations are transgenerationally inherited. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE-SOUZA, EVANDRO A.; CAMARA, HENRIQUE; SALGUEIRO, WILLIAN G.; MORO, RAISSA P.; KNITTEL, THIAGO L.; TONON, GUILHERME; PINTO, SILAS; PINCA, ANA PAULA F.; ANTEBI, ADAM; PASQUINELLI, AMY E.; et al. RNA interference may result in unexpected phenotypes in Caenorhabditis elegans. Nucleic Acids Research, v. 47, n. 8, p. 3957-3969, MAY 7 2019. (12/00195-3, 10/52557-0, 17/22057-5, 17/04377-2, 17/03423-0, 16/02207-0, 17/08829-5, 15/01316-7, 17/01339-2, 14/10814-8, 17/01184-9, 14/25068-0, 16/15958-3)

GUERRA, BEATRIZ A.; BRANDAO, BRUNA B.; PINTO, SILAS S.; SALGUEIRO, WILLIAN G.; DE-SOUZA, EVANDRO A.; REIS, FELIPE C. G.; BATISTA, THIAGO M.; CAVALCANTE-SILVA, VANESSA; D'ALMEIDA, VANIA; CASTILHO, BEATRIZ A.; et al. Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects. MOLECULAR METABOLISM, v. 29, p. 124-135, NOV 2019. (15/03292-8, 17/22057-5, 10/52557-0, 16/02207-0, 17/01184-9, 15/01316-7, 15/19530-5, 12/07259-7, 17/07975-8)

ZONARI, ALESSANDRA; BRACE, LEAR E. E.; AL-KATIB, KALLIE; PORTO, WILLIAM F. F.; FOYT, DANIEL; GUIANG, MYLIENETH; CRUZ, EDGAR ANDRES OCHOA; MARSHALL, BAILEY; GENTZ, MELISSA; GUIMARAES, GABRIELA RAPOZO; et al. Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models. NPJ AGING, v. 9, n. 1, p. 15-pg., 2023-05-22. (17/22057-5, 17/01184-9)

BRAGA, DEISI L.; MOUSOVICH-NETO, FELIPPE; TONON-DA-SILVA, GUILHERME; SALGUEIRO, WILLIAN G.; MORI, MARCELO A.. Epigenetic changes during ageing and their underlying mechanisms. BIOGERONTOLOGY, v. 21, n. 4, p. 21-pg., 2020-04-30. (19/14391-8, 17/22057-5, 17/08829-5, 18/11672-3, 17/01184-9, 18/11792-9)

BRAGA, DEISI L.; MOUSOVICH-NETO, FELIPPE; TONON-DA-SILVA, GUILHERME; SALGUEIRO, WILLIAN G.; MORI, MARCELO A.. Epigenetic changes during ageing and their underlying mechanisms. BIOGERONTOLOGY, v. 21, n. 4, SI, APR 2020. (18/11672-3, 17/22057-5, 18/11792-9, 17/08829-5, 19/14391-8, 17/01184-9)

SALGUEIRO, WILLIAN GOULART; SOARES, MARCELL VALANDRO; MARTINS, CASSIANO FIAD; PAULA, FAVERO REISDORFER; RIOS-ANJOS, RAFAELA MARIA; CARRAZONI, THIAGO; MORI, MARCELO A.; MUELLER, ROMAN-ULRICH; ASCHNER, MICHAEL; BELO, CHARISTON ANDRE DAL; et al. Dopaminergic modulation by quercetin: In silico and in vivo evidence using Caenorhabditis elegans as a model. Chemico-Biological Interactions, v. 382, p. 13-pg., 2023-09-01. (17/22057-5, 17/01184-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SALGUEIRO, Willian Goulart. Intergenerational inheritance induced by high levels of cholesterol in C. elegans is due to vitellogenin and controlled by miRNA. 2020. 57 f. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia.