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High-fat diet promotes a pro-inflammatory environment in mouse testes and inhibits certain antioxidant defenses in the testes of the progeny
1 , 2 , 3 , 4 , 5 , 6 , 7, 8 , 9 , * 1
1  Department of Microscopy, Laboratory of Cell Biology, and Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal
2  REQUINTE/LAQV, Laboratory of Pharmacognosy, Faculty of Pharmacy, University of Porto, Porto, Portugal
3  Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Portugal
4  Department of Chemistry and Biochemistry, University of Zagreb, Faculty of Veterinary Medicine
5  Department of Animal Nutrition and Dietetics, University of Zagreb, Faculty of Veterinary Medicine, Zagreb, Croatia
6  Health School of the Polytechnic Institute of Guarda, Guarda, Portugal
7  NOVA Medical School – New University Lisbon, Lisbon, Portugal
8  APDP – Diabetes Portugal, Lisbon, Portugal
9  QOPNA & LAQV, Department of Chemistry, University of Aveiro, Aveiro, Portugal

Abstract:

The adoption of high-fat diets (HFD) is a major contributor for the increasing prevalence of obesity worldwide. The adoption of unhealthy food habits happens at ever earlier age, raising concerns regarding the deleterious effects of HFD in male reproductive function and the consequences for health outcomes in the progeny. Indeed, obesity is associated to pro-inflammatory states, notably in adipose tissue. Herein we study the impact of HFD from early age in testicular physiology and sperm parameters in two generations of mice, with focus on the testicular oxidative status.

Mice of the diet-challenged generation (F0; n=36) were randomly fed after weaning with standard chow (CTRL) [Carbohydrate: 61.6%, Protein: 20.5%, Fat: 7.2% (16.3% Kcals)] or high-fat diet (HFD) [Carbohydrate: 35.7%, Protein: 20.5%, Fat: 36.0% (59.0% Kcals)] for 200 days or transient high-fat diet (HFDt) (60 days of HFD+140 days of standard chow). The offspring generation (F1; n=36) were obtained by mating with normoponderal females with 120 days post-weaning and fed with chow diet. Glucose homeostasis was evaluated and animals (F0 and F1) were sacrificed 200 days post-weaning, and tissues collected. Epididymal sperm parameters and endocrine parameters were evaluated. Testicular metabolites were extracted and characterized by 1H-NMR and GC-MS. Testicular mitochondrial and antioxidant activity were evaluated. Data were analyzed by Univariate ANOVA and Pearson’s correlation.

In generation F0, HFD reduced testicular catalase and glutathione reductase (GR) activities. Testicular content of betaine and GSH have increased in HFD too. Testicular lipid content has also elevated in HFD mice, especially in the pro-inflammatory ω6 polyunsaturated fatty acids (PUFA). HFDt partially reversed the consequences of HFD but, interestingly, both HFD and HFDt mice showed poorer sperm parameters than CTRL (lower viability and motility). In generation F1, the offspring of HFD inherited decreased catalase activity, and displayed lower activities of mitochondrial complexes I and IV, in testis. HFD offspring had lower testicular myo-inositol, and HFDt, besides this presented lower 3-hydroxibutyrate. Our data suggests that the adoption of HFD promotes a pro-inflammatory state in testis characterized by decreased activity of antioxidant enzymes and increased content in ω6 PUFAs. The adoption of HFD, even transiently, inhibits testicular antioxidant defences on itself and in the progeny, and induces specific metabolic and lipid signatures correlated to sperm quality.

Keywords: high-fat diet; intergenerational effects; pro-inflammatory state; antioxidant defences; testis
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