Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male fertility: a study using adipose triglyceride lipase deficient mice

Masaki, Hidetake; Kim, Namhyo; Nakamura, Hitomi; Kumasawa, Keiichi; Kamata, Eriko; Hirano, Ken‐ichi; Kimura, Tadashi

doi:10.1093/molehr/gax031

Cited by 27 publications

(20 citation statements)

References 19 publications

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“…As the major energy source of a spermatozoon, Fru is secreted from the seminal vesicles and is crucial for sperm survival, motility, and metabolism (Masaki et al, ). In addition, Fru is generally accepted as a biomarker of seminal vesicle function (Jayaraman et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…As the major energy source of a spermatozoon, Fru is secreted from the seminal vesicles and is crucial for sperm survival, motility, and F I G U R E 1 Extracted mass chromatograms of 27 analytes obtained in the multiple reaction monitoring mode. See text for definitions of abbreviations metabolism (Masaki et al, 2017). In addition, Fru is generally accepted as a biomarker of seminal vesicle function (Jayaraman et al, 2014).…”

Section: Energy Metabolismmentioning

confidence: 99%

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Metabolic and transcriptional changes in seminal plasma of asthenozoospermia patients

Chen

Wen

Deng

et al. 2020

Biomedical Chromatography

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This study was designed to investigate the metabolic and transcriptional alterations in seminal fluid caused by asthenozoospermia (AS). To address these issues, a method of metabonomics based on ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) and real‐time quantitative PCR (RT‐qPCR) was performed to identify some crucial biomarkers and transcription levels of the enzymes in seminal fluid. Seminal fluid samples were collected from 87 AS patients and 73 healthy males with normozoospermia. The quantitative analysis by UPLC–MS/MS showed that 19 metabolites in seminal plasma were associated with AS, and they were involved in several metabolic pathways, such as energy metabolism, purine metabolism, methionine cycle, and branched chain amino acid metabolism. Among these metabolites, the levels of citric acid, malic acid, succinic acid, and pyruvic acid, which are related to energy metabolism, were collectively reduced in the AS group, whereas the lactic acid level was enhanced. These results indicated that lesser energy source (adenosine triphosphate) was produced through the anaerobic glycolysis pathway rather than via aerobic catabolism of suger and tricarboxylic acid cycle, resulting in reduced power of sperms. Meanwhile, partial least squares discriminant analysis showed significant differences in metabolic profiles between the AS and control groups. In addition, RT‐qPCR results revealed that the expression levels of four genes encoding fructokinase citrate synthase, succinate dehydrogenase, and spermine synthase, which were related to energy metabolism, were decreased in the AS group. The 23 descriptors with differential expression in AS may be valuable for the diagnosis and sequential study on AS. These results will help highlight the role of sperm inactivity in AS pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Energy Metabolismmentioning

confidence: 99%

Metabolic and transcriptional changes in seminal plasma of asthenozoospermia patients

Chen

Wen

Deng

et al. 2020

Biomedical Chromatography

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“…Systemic deletion of ATGL leads to a pronounced TG accumulation in testis [ 62 ]. A recent study reported lower total and motile sperm concentrations upon systemic ATGL knockout suggesting impaired spermatogenesis and sperm maturation [ 208 ]. However, systemic ATGL knockout with rescued heart function [ 71 , 77 ] were bred using heterozygous females and homozygous males and produced siblings (unpublished data).…”

Section: What We Have Learnt From Mouse Models and Patientsmentioning

confidence: 99%

Of mice and men: The physiological role of adipose triglyceride lipase (ATGL)

Schreiber

Xie

Schweiger

2019

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

114

106

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Adipose triglyceride lipase (ATGL) has been discovered 14 years ago and revised our view on intracellular triglyceride (TG) mobilization – a process termed lipolysis. ATGL initiates the hydrolysis of TGs to release fatty acids (FAs) that are crucial energy substrates, precursors for the synthesis of membrane lipids, and ligands of nuclear receptors. Thus, ATGL is a key enzyme in whole-body energy homeostasis. In this review, we give an update on how ATGL is regulated on the transcriptional and post-transcriptional level and how this affects the enzymes' activity in the context of neutral lipid catabolism. In depth, we highlight and discuss the numerous physiological functions of ATGL in lipid and energy metabolism. Over more than a decade, different genetic mouse models lacking or overexpressing ATGL in a cell- or tissue-specific manner have been generated and characterized. Moreover, pharmacological studies became available due to the development of a specific murine ATGL inhibitor (Atglistatin®). The identification of patients with mutations in the human gene encoding ATGL and their disease spectrum has underpinned the importance of ATGL in humans. Together, mouse models and human data have advanced our understanding of the physiological role of ATGL in lipid and energy metabolism in adipose and non-adipose tissues, and of the pathophysiological consequences of ATGL dysfunction in mice and men.

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“…Plasma NEFA, as the major source of fatty acids for TG synthesis, causes abnormal lipid accumulation, which leads to the development of NAFLD [32,33]. In the present study, the content of TG was measured with an enzyme-linked immunosorbent assay, which indicated that NEFA stimulated TG synthesis and secretion or insulin resistance, resulting in the accumulation of TG.…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 64%

NEFA-Sensitive Orai1 Expression in Regulation of De Novo Lipogenesis

Zhang¹,

Yang²,

Zou³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Non-esterified fatty acids (NEFAs) are important inducers of inflammatory responses and hepatic lipid accumulation, which lead to non-alcoholic fatty liver disease (NAFLD). High plasma NEFA is found in NAFLD patients, and associated with metabolic syndrome and type-2 diabetes. NFκB is known to upregulate Orai1, the Ca²⁺ channel responsible for store-operated Ca²⁺ entry. The present study explored the role of NEFA-sensitive NFκB-dependent Orai1 expression in the regulation of lipid synthesis. Methods: BRL-3A rat liver hepatocyte lines were studied in the absence and presence of NEFA. Transcript and protein expression levels of factors involved in lipid synthesis were quantified by quantitative polymerase chain reaction (qPCR) and western blot analyses. Fatty acids were measured by immunofluorescence. Results: NEFA significantly increased, as indicated by the expression of sterol regulatory element-binding protein 1 (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase α (ACC1), Orai1, and NFκB p65 by qPCR and western blot analyses. These effects were reversed by the Orai1 inhibitor, 2-aminoethoxydiphenyl borate, and the NFκB inhibitor, wogonin. Furthermore, SREBP-1c, FAS, ACC1, and Orai1 were significantly decreased by Orai1 silencing. Conclusions: Taken together, these results demonstrated that NEFA-sensitive NFκB-dependent Orai1 expression regulates de novo lipogenesis.

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Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male fertility: a study using adipose triglyceride lipase deficient mice

Abstract: This study was supported in part by the Japan Society for the Promotion of Science JSPS KAKENHI Grant (Nos. JP24249080, JP25462557, JP16K11086). The authors declare no conflict of interest.

Cited by 27 publications

References 19 publications

Metabolic and transcriptional changes in seminal plasma of asthenozoospermia patients

Metabolic and transcriptional changes in seminal plasma of asthenozoospermia patients

Of mice and men: The physiological role of adipose triglyceride lipase (ATGL)

NEFA-Sensitive Orai1 Expression in Regulation of De Novo Lipogenesis

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