TY - JOUR
T1 - Inherited Metabolic Memory of High-Fat Diet Impairs Testicular Fatty Acid Content and Sperm Parameters
AU - Crisóstomo, Luís
AU - Videira, Romeu A.
AU - Jarak, Ivana
AU - Starčević, Kristina
AU - Mašek, Tomislav
AU - Rato, Luís
AU - Raposo, João F.
AU - Batterham, Rachel L.
AU - Oliveira, Pedro F.
AU - Alves, Marco G.
N1 - Funding Information:
This work was supported by the Portuguese Foundation for Science and Technology: L.C. (SFRH/BD/128584/2017), M.G.A. (IFCT2015 and PTDC/MEC‐AND/28691/2017), P.F.O. (IFCT2015), UMIB (UIDB/00215/2020 and UIDP/00215/2020), ITR (LA/P/0064/2020), and QOPNA (UID/QUI/00062/2019) co‐funded by FEDER funds (POCI/COMPETE 2020); by the Portuguese Society of Diabetology: L.C. and M.G.A. (“Nuno Castel‐Branco” research grant and Group of Fundamental and Translational Research); and by the Croatian Science Foundation: K.S. (IP‐2016‐06‐3163). NMR data were collected at the UC‐NMR facility which is supported in part by FEDER – European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through grants REEQ/481/QUI/2006, RECI/QEQ‐QFI/0168/2012, CENTRO‐07‐CT62‐FEDER‐002012, and Rede Nacional de Ressonância Magnética Nuclear (RNRMN). The authors thank Matthieu Bourgery (University of Turku) for his advice on statistical methods.
Publisher Copyright:
© 2022 Wiley-VCH GmbH
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122660137&partnerID=8YFLogxK
U2 - 10.1002/mnfr.202100680
DO - 10.1002/mnfr.202100680
M3 - Article
AN - SCOPUS:85122660137
SN - 1613-4125
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
M1 - 2100680
ER -