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



: Crisostomo L, Videira RA, Jarak I, Starcevic K, Masek T, Rato L, Raposo JF, Batterham RL, Oliveira PF, Alves MG

Publisher: WILEY

: 2022

: Molecular Nutrition and Food Research

: MOLECULAR NUTRITION & FOOD RESEARCH

: MOL NUTR FOOD RES

:  2100680

: 66

: 14

: 1613-4125

DOI: https://doi.org/10.1002/mnfr.202100680

: https://onlinelibrary.wiley.com/doi/full/10.1002/mnfr.202100680


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 H-1-NMR and GC-MS. Sons of HFD display impaired choline metabolism, mitochondrial activity, and antioxidant defenses, while grandsons show a shift in testicular omega 3/omega 6 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.

Last updated on 2024-26-11 at 12:08