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Crisostomo 2019 MiP2019
Has abstract [[Image:MITOEAGLE-logo.jpg|left|100px|link
[[Image:MITOEAGLE-logo.jpg|left|100px|link=|COST Action MitoEAGLE]] Despite global efforts to curb the “fat epidemic”, the prevalence of Obesity and related comorbidities, such as diabetes mellitus (DM), is expected to keep its upward trend in the next decades. The temporal trends on sperm parameters [1], have recently raised concern about the burden of metabolic disease in male reproductive potential. High-fat diet (HFD) is regarded as one of the main causes for the “fat epidemics” [2], but it is unclear whether its deleterious effects are inherited by the offspring, by factors carried by the male gamete. In a recently published study, our group have showed how high-fat diets induce irreversible changes in murine sperm parameters [3], even after diet reversion (DR). Additionally, we have successfully correlated HFD to changes in testicular metabolome which led to anomalies in sperm parameters. Herein we aimed to clarify whether mitochondrial function was affected by HFD and if sperm defects were observed in the offspring. To pursuit this hypothesis, 3 groups of 12 mice were fed with distinct diets (CTRL – standard mucedola; HFD and HFD<sub>t</sub> – HFD for 60 days, then replaced by standard mucedola). This population comprised the paternal generation (F<sub>0</sub>) Animals were kept in environmental challenging cages for 200 days after weaning, with unrestricted water and food supply. Mice weight, and food and water intake were monitored. After sacrifice, several tissues were collected and weighed. Testicular tissue was used for metabolomics analysis by <sup>1</sup>H-NMR, and for mitochondrial isolation. Sperm was obtained from epididymis, and mice fertility determined. Western blotting was performed to quantify protein expression of mitochondrial complexes. Individual complexes and citrate synthase activity were further assessed. 120 days post-weaning, males were mated with normoponderal females (1:1) to generate offspring. The same protocols were applied to the resulting offspring generation (F<sub>1</sub>), but all animals were fed with a standard diet. We have previously demonstrated that metabolic pathways directly associated with mitochondrial function were dysregulated in testis of HFD-fed mice, even if transiently. However, no changes were observed on the individual activity of any of the complexes assessed, nor in citrate synthase. Similarly, no changes were observed in complex expression. Strikingly, Complex I activity was significantly decreased in the offspring of HFD comparing to the offspring of CTRL mice. No further changes were observed in the activity nor expression of mitochondrial complexes in the offspring. We were able to trace the global burden of HFD in the offspring testis to branched-chain amino acid metabolism and GSH metabolism, integrating NMR data on MetaboAnalyst 4.0 [4]. Overall our data suggest that HFD has a small impact in the mitochondrial fitness of the testicular tissue, in the diet-challenged animals, but its effects are amplified in the offspring of these mice. Thus, HFD might cause a transgenerational effect in testicular mitochondria, that may be more evident in generations unexposed to HFD (F<sub>1</sub> and, possibly, F<sub>2</sub> generations). Therefore, paternal HFD leaves a “ghost” signature in mitochondria of the male lineage, that may be expressed in future generations as a pathological phenotype of metabolic dysfunction, without apparent exposure.
ic dysfunction, without apparent exposure.  +
Has editor [[Plangger M]]  + , [[Tindle-Solomon L]]  +
Has title [[Image:CrisostomoL.JPG|left|90px|Luís Crisóstomo]] “Mitogheist” – Is testicular mitochondrial dysfunction a ghost pattern of paternal high-fat diet in mice?  +
Mammal and model Mouse  +
MiP area Exercise physiology;nutrition;life style  + , Developmental biology  +
Tissue and cell Genital  +
Was submitted in year 2019  +
Was submitted to event MiP2019/MitoEAGLE Belgrade RS +
Was written by Crisostomo L + , Rato L + , Jarak I + , Videira RA + , Silva BM + , Raposo JF + , Oliveira PF + , Alves MG +
Categories Abstracts
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
12:05:21, 12 September 2019  +
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