دورية أكاديمية
Futile cycle of β-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy.
| العنوان: | Futile cycle of β-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy. |
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| المؤلفون: | Chaves-Filho AB; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 748, São Paulo 05508900, Brazil; Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof Lineu Prestes 1524, São Paulo 05508000, Brazil. Electronic address: adrianobcfilho@gmail.com., Peixoto AS; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 748, São Paulo 05508900, Brazil., Castro É; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 748, São Paulo 05508900, Brazil., Oliveira TE; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 748, São Paulo 05508900, Brazil., Perandini LA; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 748, São Paulo 05508900, Brazil., Moreira RJ; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 748, São Paulo 05508900, Brazil., da Silva RP; Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof Lineu Prestes 1524, São Paulo 05508000, Brazil., da Silva BP; Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof Lineu Prestes 1524, São Paulo 05508000, Brazil., Moretti EH; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 1524, São Paulo 05508000, Brazil., Steiner AA; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 1524, São Paulo 05508000, Brazil., Miyamoto S; Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof Lineu Prestes 1524, São Paulo 05508000, Brazil., Yoshinaga MY; Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof Lineu Prestes 1524, São Paulo 05508000, Brazil. Electronic address: marcosyukio@gmail.com., Festuccia WT; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes 748, São Paulo 05508900, Brazil. Electronic address: william.festuccia@usp.br. |
| المصدر: | Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2023 Mar; Vol. 1868 (3), pp. 159264. Date of Electronic Publication: 2022 Dec 17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731727 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-2618 (Electronic) Linking ISSN: 13881981 NLM ISO Abbreviation: Biochim Biophys Acta Mol Cell Biol Lipids Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier |
| مواضيع طبية MeSH: | Lipogenesis* , Fatty Liver*/metabolism, Animals ; Mice ; Substrate Cycling ; Lipid Metabolism ; alpha-Linolenic Acid/metabolism |
| مستخلص: | Total absence of adipose tissue (lipoatrophy) is associated with the development of severe metabolic disorders including hepatomegaly and fatty liver. Here, we sought to investigate the impact of severe lipoatrophy induced by deletion of peroxisome proliferator-activated receptor gamma (PPARγ) exclusively in adipocytes on lipid metabolism in mice. Untargeted lipidomics of plasma, gastrocnemius and liver uncovered a systemic depletion of the essential linoleic (LA) and α-linolenic (ALA) fatty acids from several lipid classes (storage lipids, glycerophospholipids, free fatty acids) in lipoatrophic mice. Our data revealed that such essential fatty acid depletion was linked to increased: 1) capacity for liver mitochondrial fatty acid β-oxidation (FAO), 2) citrate synthase activity and coenzyme Q content in the liver, 3) whole-body oxygen consumption and reduced respiratory exchange rate in the dark period, and 4) de novo lipogenesis and carbon flux in the TCA cycle. The key role of de novo lipogenesis in hepatic steatosis was evidenced by an accumulation of stearic, oleic, sapienic and mead acids in liver. Our results thus indicate that the simultaneous activation of the antagonic processes FAO and de novo lipogenesis in liver may create a futile metabolic cycle leading to a preferential depletion of LA and ALA. Noteworthy, this previously unrecognized cycle may also explain the increased energy expenditure displayed by lipoatrophic mice, adding a new piece to the metabolic regulation puzzle in lipoatrophies. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Fatty acid oxidation; Linoleic acid; Lipoatrophy; Peroxisome proliferator-activated receptor gamma (PPARγ); de novo lipogenesis; α-Linolenic acid |
| المشرفين على المادة: | 0RBV727H71 (alpha-Linolenic Acid) |
| تواريخ الأحداث: | Date Created: 20221219 Date Completed: 20230120 Latest Revision: 20230224 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.bbalip.2022.159264 |
| PMID: | 36535597 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-2618 |
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| DOI: | 10.1016/j.bbalip.2022.159264 |