engleski

Inherited metabolic memory of high-fat diet impairs testicular fatty acid content and sperm parameters

High-fat diet (HFD) in early-age is a threat to metabolic and reproductive health. Recently, evidence emerged on paternally-mediated inheritance of metabolic signatures induced by exposure to HFDs. Hereby, we expand our previous studies on “inherited metabolic memory” in testis, focusing on lipid signatures caused by ancestral diet in two subsequent generations. Diet- challenged mice (n=36) were randomly fed after weaning with standard chow (CTRL) [Carbohydrate: 61.6%, Protein: 20.5%, Fat: 7.2% (16.3% Kcals)] ; HFD [Carbohydrate: 35.7%, Protein: 20.5%, Fat: 36.0% (59.0% Kcals)] for 200 days or transient HFD (HFDt) (60 days of HFD+140 days of standard chow). Subsequent generations (36 mice per generation) were obtained by mating F0 and F1 males 120 days post-weaning with normoponderal females and fed with chow diet. Glucose homeostasis was evaluated and animals (F0, F1 and F2) were sacrificed 200 days post-weaning. Tissues were collected, and epididymal sperm parameters and endocrine parameters evaluated. Testicular metabolites were extracted and characterized by 1H-NMR and GC-MS. Testicular mitochondrial and antioxidant activity were evaluated. Exploratory Data Analysis based on sPLS-DA and sPLS was performed. Paternal ancestral exposure to HFD, even transiently, changed testicular lipids metabolism and lipid precursors in descendants (F1 and F2). sPLS-DA and sPLS show that testicular lipid signatures are specific to each experimental group. The adoption of a HFD, even transiently, induces inter- and transgenerational lipids signatures in testis that is related to decreased sperm quality for up to two generations. Yet, this “acquired metabolic memory” withholds specific signatures on lipids depending on the ancestral paternal diet, even if transient during childhood

High-fat diet ; lipidomics ; paternal inheritance, sPLS-DA, inherited metabolic memory

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