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Property "Has-20abstract" (as page type) with input value "-5B-5BImage:MITOEAGLE-2Dlogo.jpg-7Cleft-7C100px-7Clink=http:-2F-2Fwww.mitoglobal.org-2Findex.php-2FMITOEAGLE-7CCOST-20Action-20MitoEAGLE-5D-5D-0ADespite-20global-20efforts-20to-20curb-20the-20“fat-20epidemic”,-20the-20prevalence-20of-20Obesity-20and-20related-20comorbidities,-20such-20as-20diabetes-20mellitus-20(DM),-20is-20expected-20to-20keep-20its-20upward-20trend-20in-20the-20next-20decades.-20The-20temporal-20trends-20on-20sperm-20parameters-20-5B1-5D,-20have-20recently-20raised-20concern-20about-20the-20burden-20of-20metabolic-20disease-20in-20male-20reproductive-20potential.-20High-2Dfat-20diet-20(HFD)-20is-20regarded-20as-20one-20of-20the-20main-20causes-20for-20the-20“fat-20epidemics”-20-5B2-5D,-20but-20it-20is-20unclear-20whether-20its-20deleterious-20effects-20are-20inherited-20by-20the-20offspring,-20by-20factors-20carried-20by-20the-20male-20gamete.-20-0A-0AIn-20a-20recently-20published-20study,-20our-20group-20have-20showed-20how-20high-2Dfat-20diets-20induce-20irreversible-20changes-20in-20murine-20sperm-20parameters-20-5B3-5D,-20even-20after-20diet-20reversion-20(DR).-20-20Additionally,-20we-20have-20successfully-20correlated-20HFD-20to-20changes-20in-20testicular-20metabolome-20which-20led-20to-20anomalies-20in-20sperm-20parameters.-20Herein-20we-20aimed-20to-20clarify-20whether-20mitochondrial-20function-20was-20affected-20by-20HFD-20and-20if-20sperm-20defects-20were-20observed-20in-20the-20offspring.-0A-0ATo-20pursuit-20this-20hypothesis,-203-20groups-20of-2012-20mice-20were-20fed-20with-20distinct-20diets-20(CTRL-20–-20standard-20mucedola-3B-20HFD-20and-20HFD-3Csub-3Et-3C-2Fsub-3E-20–-20HFD-20for-2060-20days,-20then-20replaced-20by-20standard-20mucedola).-20This-20population-20comprised-20the-20paternal-20generation-20(F-3Csub-3E0-3C-2Fsub-3E)-20Animals-20were-20kept-20in-20environmental-20challenging-20cages-20for-20200-20days-20after-20weaning,-20with-20unrestricted-20water-20and-20food-20supply.-20Mice-20weight,-20and-20food-20and-20water-20intake-20were-20monitored.-20After-20sacrifice,-20several-20tissues-20were-20collected-20and-20weighed.-20Testicular-20tissue-20was-20used-20for-20metabolomics-20analysis-20by-20-3Csup-3E1-3C-2Fsup-3EH-2DNMR,-20and-20for-20mitochondrial-20isolation.-20Sperm-20was-20obtained-20from-20epididymis,-20and-20mice-20fertility-20determined.-20Western-20blotting-20was-20performed-20to-20quantify-20protein-20expression-20of-20mitochondrial-20complexes.-20Inspanidual-20complexes-20and-20citrate-20synthase-20activity-20were-20further-20assessed.-20120-20days-20post-2Dweaning,-20males-20were-20mated-20with-20normoponderal-20females-20(1:1)-20to-20generate-20offspring.-20The-20same-20protocols-20were-20applied-20to-20the-20resulting-20offspring-20generation-20(F-3Csub-3E1-3C-2Fsub-3E),-20but-20all-20animals-20were-20fed-20with-20a-20standard-20diet.-0A-0AWe-20have-20previously-20demonstrated-20that-20metabolic-20pathways-20directly-20associated-20with-20mitochondrial-20function-20were-20dysregulated-20in-20testis-20of-20HFD-2Dfed-20mice,-20even-20if-20transiently.-20However,-20no-20changes-20were-20observed-20on-20the-20inspanidual-20activity-20of-20any-20of-20the-20complexes-20assessed,-20nor-20in-20citrate-20synthase.-20Similarly,-20no-20changes-20were-20observed-20in-20complex-20expression.-20Strikingly,-20Complex-20I-20activity-20was-20significantly-20decreased-20in-20the-20offspring-20of-20HFD-20comparing-20to-20the-20offspring-20of-20CTRL-20mice.-20No-20further-20changes-20were-20observed-20in-20the-20activity-20nor-20expression-20of-20mitochondrial-20complexes-20in-20the-20offspring.-20We-20were-20able-20to-20trace-20the-20global-20burden-20of-20HFD-20in-20the-20offspring-20testis-20to-20branched-2Dchain-20amino-20acid-20metabolism-20and-20GSH-20metabolism,-20integrating-20NMR-20data-20on-20MetaboAnalyst-204.0-20-5B4-5D.-0A-0AOverall-20our-20data-20suggest-20that-20HFD-20has-20a-20small-20impact-20in-20the-20mitochondrial-20fitness-20of-20the-20testicular-20tissue,-20in-20the-20diet-2Dchallenged-20animals,-20but-20its-20effects-20are-20amplified-20in-20the-20offspring-20of-20these-20mice.-20Thus,-20HFD-20might-20cause-20a-20transgenerational-20effect-20in-20testicular-20mitochondria,-20that-20may-20be-20more-20evident-20in-20generations-20unexposed-20to-20HFD-20(F-3Csub-3E1-3C-2Fsub-3E-20and,-20possibly,-20F-3Csub-3E2-3C-2Fsub-3E-20generations).-20Therefore,-20paternal-20HFD-20leaves-20a-20“ghost”-20signature-20in-20mitochondria-20of-20the-20male-20lineage,-20that-20may-20be-20expressed-20in-20future-20generations-20as-20a-20pathological-20phenotype-20of-20metabolic-20dysfunction,-20without-20apparent-20exposure." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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