Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects

Author(s):Show less -

Guerra, Beatriz A. ^{[1, 2, 3]} ; Brandao, Bruna B. ^{[1, 3]} ; Pinto, Silas S. ^{[1, 2, 4, 3]} ; Salgueiro, Willian G. ^{[2, 4]} ; De-Souza, Evandro A. ^{[1, 5, 3]} ; Reis, Felipe C. G. ^[1] ; Batista, Thiago M. ^[6] ; Cavalcante-Silva, Vanessa ^[7] ; D'Almeida, Vania ^[7] ; Castilho, Beatriz A. ^[8] ; Carneiro, Everardo M. ^[6] ; Antebi, Adam ^{[9, 10]} ; Festuccia, William T. ^[11] ; Mori, Marcelo A. ^{[1, 2, 4, 3]}

Affiliation:Show less -

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[3] Univ Fed Sao Paulo, Escola Paulista Med, Program Mol Biol, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, Inst Biol, Program Genet & Mol Biol, Campinas, SP - Brazil

^[5] Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro - Brazil

^[6] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[7] Univ Fed Sao Paulo, Escola Paulista Med, Dept Psychobiol, Sao Paulo - Brazil

^[8] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[9] Max Planck Inst Biol Ageing, Cologne - Germany

^[10] Univ Cologne, CECAD, Cologne - Germany

^[11] Univ Sao Paulo, Inst Ciencias Biomed, Dept Physiol, Sao Paulo - Brazil

• Document type: Journal article
• Source: MOLECULAR METABOLISM; v. 29, p. 124-135, NOV 2019.
• Web of Science Citations: 0

Abstract

Objective: Dietary restriction (DR) improves health and prolongs lifespan in part by upregulating type III endoribonuclease DICER in adipose tissue. In this study, we aimed to specifically test which missing dietary component was responsible for DICER upregulation. Methods: We performed a nutrient screen in mouse preadipocytes and validated the results in vivo using different kinds of dietary interventions in wild type or genetically modified mice and worms, also testing the requirement of DICER on the effects of the diets. Results: We found that sulfur amino acid restriction (i.e., methionine or cysteine) is sufficient to increase Dicer mRNA expression in preadipocytes. Consistently, while DR increases DICER expression in adipose tissue of mice, this effect is blunted by supplementation of the diet with methionine, cysteine, or casein, but not with a lipid or carbohydrate source. Accordingly, dietary methionine or protein restriction mirrors the effects of DR. These changes are associated with alterations in serum adiponectin. We also found that DICER controls and is controlled by adiponectin. In mice, DICER plays a role in methionine restriction-induced upregulation of Ucpl in adipose tissue. In C. elegans, DR and a model of methionine restriction also promote DICER expression in the intestine (an analog of the adipose tissue) and prolong lifespan in a DICER-dependent manner. Conclusions: We propose an evolutionary conserved mechanism in which dietary sulfur amino acid restriction upregulates DICER levels in adipose tissue leading to beneficial health effects. (C) 2019 The Authors. Published by Elsevier GmbH. (AU)

• FAPESP's process: 15/03292-8 - Study of the role of GCN1 in the genesis of metabolic diseases in mice
• Grantee: Beatriz Alves Guerra
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/22057-5 - Physiological effects and transgenerational inheritance induced by cholesterol-rich diet in Caenorhabditis elegans
• Grantee: Willian Goulart Salgueiro
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 10/52557-0 - Identification of mechanisms responsible for beneficial effects of calorie restriction
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/02207-0 - Identification of soma-germline interactions that may influence lifespan in Caenorhabditis elegans
• Grantee: Evandro Araújo de Souza
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/01316-7 - Dicer, miRNAs and the control of mitochondrial function in the context of aging and caloric restriction
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/07259-7 - Evaluation of miRNA Processing in Adipose Tissue of Mice Subjected to Caloric Restriction
• Grantee: Beatriz Alves Guerra
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/07975-8 - Exploring the role of adipose tissue-derived circulating miRNAs in the beneficial effects of exercise training
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Regular Research Grants