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.
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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 |
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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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