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Inherited Metabolic Memory of High-Fat Diet Impairs Testicular Fatty Acid Content and Sperm Parameters

Crisostomo, Luis; Videira, Romeu A; Jarak, Ivana; Starcevic, Kristina; Masek, Tomislav; Rato, Luis; Raposo, Joao F; ... Alves, Marco G; + view all (2022) Inherited Metabolic Memory of High-Fat Diet Impairs Testicular Fatty Acid Content and Sperm Parameters. Molecular Nutrition and Food Research , 66 (5) , Article 2100680. 10.1002/mnfr.202100680. Green open access

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Abstract

Scope: Exposure to a high-fat diet (HFD) from early-life is associated with a testicular metabolic signature link to abnormal sperm parameters up to two generations after exposure in mice. Hereby, this study describes a testicular lipid signature associate with “inherited metabolic memory” of exposure to HFD, persisting up to two generations in mice. Methods and Results: Diet-challenged mice (n = 36) are randomly fed after weaning with standard chow (CTRL); HFD for 200 days or transient HFD (HFDt) (60 days of HFD + 140 days of standard chow). Subsequent generations (36 mice per generation) are fed with chow diet. Mice are euthanized 200 days post-weaning. Glucose homeostasis, serum hormones, testicular bioenergetics, and antioxidant enzyme activity are evaluated. Testicular lipid-related metabolites and fatty acids are characterized by 1H-NMR and GC-MS. Sons of HFD display impaired choline metabolism, mitochondrial activity, and antioxidant defenses, while grandsons show a shift in testicular ω3/ω6 ratio towards a pro-inflammatory environment. Grandsons of HFDt raise 3-hydroxybutyrate levels with possible implications to testicular insulin resistance. Sperm counts decrease in grandsons of HFD-exposed mice, regardless of the duration of exposure. Conclusion: HFD-induced “inherited metabolic memory” alters testicular fatty acid metabolism with consequences to sperm parameters up to two generations.

Type: Article
Title: Inherited Metabolic Memory of High-Fat Diet Impairs Testicular Fatty Acid Content and Sperm Parameters
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/mnfr.202100680
Publisher version: https://doi.org/10.1002/mnfr.202100680
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: discriminant analysis, high-fat diet, inherited metabolic memory, lipidomics, paternal inheritance, testis, TRANSGENERATIONAL INHERITANCE, MOUSE, MODULATION, EXPOSURE, OBESITY, PROFILE, SIZE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10162708
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