SIRT6 in mouse spermatogenesis is modulated by diet-induced obesity

2011 ◽  
Vol 23 (7) ◽  
pp. 929 ◽  
Author(s):  
Nicole O. Palmer ◽  
Tod Fullston ◽  
Megan Mitchell ◽  
Brian P. Setchell ◽  
Michelle Lane
Keyword(s):  
Dna Damage ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Male Mice ◽  
High Fat ◽  
Sperm Dna Damage ◽  
Diet Induced Obesity ◽  
Damage Repair ◽  
Sperm Dna

Male obesity is associated with reduced sperm function and increased incidence of sperm DNA damage; however, the underlying molecular mechanisms have not yet been identified. Mammalian SIRT6 protein is involved in caloric-dependant DNA damage repair in other tissue types, yet a possible role for SIRT6 in male obesity and subfertility has not been investigated previously. To assess SIRT6 levels and activity in the testes, male mice (n = 12 per diet) were fed either a control diet (CD; 6% fat) or a high-fat diet (HFD; 21% fat) for 16 weeks before the collection of testes and spermatozoa. SIRT6 protein was localised to the nucleus of transitional spermatids and the acrosome of mature spermatozoa, with levels significantly decreased in HFD-fed male mice (P < 0.05). This decrease in SIRT6 protein was associated with transitional spermatids having increased levels of acetylated H3K9 in the nucleus (P < 0.01) and increased DNA damage (P < 0.001). We propose a role for SIRT6 in spermiogenesis and potentially protamination processes, which are known to be compromised by male obesity.

181. SIRT6 PROTEIN IS REDUCED IN TESTES AND SPERM FROM OBESE MALE MICE

2010 ◽  
Vol 22 (9) ◽  
pp. 99
Author(s):  
N. O. Palmer ◽  
T. Fullston ◽  
M. Mitchell ◽  
M. Lane
Keyword(s):  
Dna Damage ◽  
Control Diet ◽  
Caloric Intake ◽  
Cell Types ◽  
Mature Sperm ◽  
Mrna Levels ◽  
Male Mice ◽  
Sperm Dna Damage ◽  
Damage Repair ◽  
Sperm Dna

Obesity in males is associated with altered hormone levels, reduced sperm function and increased sperm DNA damage. However, the underlying molecular mechanism has not been identified. Mammalian SIRT6 protein exhibits caloric intake dependant DNA damage repair in other tissue types. However, a possible role for SIRT6 in male obesity and subfertility has not been considered. Therefore, the aim of this study was to assess the effects of male obesity on SIRT6 in testes and mature sperm. Five week old C57BL6 male mice (n =10 per diet) were fed either a control diet (CD) (6% fat) or a high fat diet (HFD) (21% fat) for 16 weeks before collection of sperm and testes. There was no difference in Sirt6 mRNA levels as determined by qPCR in testes from HFD males. Immunohistochemistry showed SIRT6 localised to the nucleus of transitioningspermatids from late round spermatidsuntil early elongating spermatids. SIRT6 relative fluorescence of these positive cell types was significantly decreased by 22% in males fed the HFD compared to CD (P < 0.05). This was confirmed by a decrease in total SIRT6 protein in testes from HFD males as detected by an immunoabsorbance assay (P < 0.05). Surprisingly, SIRT6 was only present in the acrosome of mature sperm. Acrosomal localisation was confirmed by the loss of SIRT6 staining after an induced acrosome reaction. SIRT6 levels in the acrosome of mature sperm was decreased by 11% in males fed the HFD (P < 0.05). This is the first study to show that SIRT6 is located to the acrosome of mature sperm, specific cells within the testes and is reduced in an obese state. Furthermore, this study suggests a possible role for SIRT6 in the acrosomal reaction and therefore potentially fertilisation, processes which are known to be reduced by male obesity.

Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function

2012 ◽  
Vol 302 (7) ◽  
pp. E768-E780 ◽  
Author(s):  
Nicole O. Palmer ◽  
Hassan W. Bakos ◽  
Julie A. Owens ◽  
Brian P. Setchell ◽  
Michelle Lane
Keyword(s):  
Dna Damage ◽  
Sperm Motility ◽  
Serum Cholesterol ◽  
High Fat Diet ◽  
Sperm Function ◽  
High Fat ◽  
Exercise Interventions ◽  
Sperm Dna Damage ◽  
Sperm Dna ◽  
Diet And Exercise

Male obesity is associated with reduced sperm motility and morphology and increased sperm DNA damage and oxidative stress; however, the reversibility of these phenotypes has never been studied. Therefore, the aim of this study was to assess the reversibility of obesity and its associated sperm physiology and function in mice in response to weight loss through diet and exercise. C57BL6 male mice ( n = 40) were fed either a control diet (CD; 6% fat) or a high-fat diet (HFD; 21% fat) for 10 wk before allocation to either diet and/or swimming exercise interventions for 8 wk. Diet alone reduced adiposity (1.6-fold) and serum cholesterol levels (1.7-fold, P < 0.05), while exercise alone did not alter these, but exercise plus diet also improved glucose tolerance (1.3-fold, P < 0.05). Diet and/or exercise improved sperm motility (1.2-fold) and morphology (1.1-fold, P < 0.05), and reduced sperm DNA damage (1.5-fold), reactive oxygen species (1.1-fold), and mitochondrial membrane potential (1.2-fold, P < 0.05) and increased sperm binding (1.4-fold) ( P < 0.05). Sperm parameters were highly correlated with measures of glycemia, insulin action, and serum cholesterol (all P < 0.05) regardless of adiposity or intervention, suggesting a link between systemic metabolic status and sperm function. This is the first study to show that the abnormal sperm physiology resulting from obesity can be reversed through diet and exercise, even in the presence of ongoing obesity, suggesting that diet and lifestyle interventions could be a combined approach to target subfertility in overweight and obese men.

Leuconostoc mesenteroides subsp. mesenteroides SD23 Prevents Metabolic Dysfunction Associated with High-Fat Diet–Induced Obesity in Male Mice

2019 ◽  
Vol 12 (2) ◽  
pp. 505-516 ◽  
Author(s):  
Diana C. Castro-Rodríguez ◽  
Luis A. Reyes-Castro ◽  
Claudia C. Vega ◽  
Guadalupe L. Rodríguez-González ◽  
Jorge Yáñez-Fernández ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Leuconostoc Mesenteroides ◽  
Metabolic Dysfunction ◽  
Male Mice ◽  
High Fat ◽  
Diet Induced Obesity

scholarly journals Blockade of High-Fat Diet Proteomic Phenotypes using Exercise as Prevention or Treatment

2020 ◽  
pp. mcp.TIR120.002343
Author(s):  
Sergio F Martinez-Huenchullan ◽  
Isaac Shipsey ◽  
Luke Hatchwell ◽  
Danqing Min ◽  
Stephen M Twigg ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Saturated Fat ◽  
Interval Training ◽  
Plasma Proteome ◽  
High Fat ◽  
Endurance Running ◽  
Interactive Visualizations

The increasing consumption of high-fat foods combined with a lack of exercise is a major contributor to the burden of obesity in humans. Aerobic exercise such as running is known to provide metabolic benefits, but how the over-consumption of a high fat diet (HFD) and exercise interact is not well characterized at the molecular level. Here, we examined the plasma proteome in mice for the effects of aerobic exercise as both a treatment and as a preventative regime for animals on either HFD or a healthy control diet. This analysis detected large changes in the plasma proteome induced by the HFD, such as increased abundance of SERPINA7, ALDOB, and down-regulation of SERPINA1E, CFD (adipsin). Some of these changes were significantly reverted using exercise as a preventative measure, but not as a treatment regime. To determine if either the intensity, or duration, of exercise influenced the outcome, we compared high-intensity interval training (HIIT) and endurance running. Endurance running slightly out-performed HIIT exercise, but overall, both provided similar reversion in abundance of plasma proteins modulated by the high-fat diet including SERPINA7, APOE, SERPINA1E, and CFD. Finally, we compared the changes induced by over-consumption of HFD to previous data from mice fed an isocaloric high saturated fat (SFA) or polyunsaturated fat (PUFA) diet. This identified several common changes including increased APOC2 and APOE, but also highlighted changes specific for either over-consumption of HFD (ALDOB, SERPINA7, CFD), SFA-based diets (SERPINA1E), or PUFA-based diets (Haptoglobin - Hp). Together, these data highlight the importance of early intervention with exercise to revert HFD-induced phenotypes and suggest some of the molecular mechanisms leading to the changes in the plasma proteome generated by high fat diet consumption. Web-based interactive visualizations are provided for this dataset (larancelab.com/hfd-exercise), which give insight into diet and exercise phenotypic interactions on the plasma proteome.

Therapeutic effects of açaí seed extract on hepatic steatosis in high‐fat diet‐induced obesity in male mice: a comparative effect with rosuvastatin

2020 ◽  
Vol 72 (12) ◽  
pp. 1921-1932
Author(s):  
Thamires Barros Tavares ◽  
Izabelle Barcellos Santos ◽  
Graziele Freitas Bem ◽  
Dayane Teixeira Ognibene ◽  
Ana Paula Machado Rocha ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Seed Extract ◽  
Therapeutic Effects ◽  
Male Mice ◽  
High Fat ◽  
Comparative Effect ◽  
Diet Induced Obesity

scholarly journals Effects of Diet-Induced Obesity and Deficient in Vitamin D on Spermatozoa Function and DNA Integrity in Sprague-Dawley Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
O. Merino ◽  
R. Sánchez ◽  
B. M. Gregorio ◽  
F. J. Sampaio ◽  
J. Risopatrón
Keyword(s):  
Vitamin D ◽  
Dna Fragmentation ◽  
High Fat Diet ◽  
Control Diet ◽  
Sperm Function ◽  
Sprague Dawley ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
The Impact

Obesity has adverse effects on male fertility and usually is diagnosed with a prevalence of vitamin D deficiency (VD-). Discussion on the impact of obesity/VD- on sperm function has been limited. This study analyzed the effects of diet-induced obesity/VD- on viability and plasma membrane integrity (PMI), superoxide anion (O2-) level, and DNA fragmentation (DNAfrag) in sperm Sprague-Dawley rats. The males were randomized into four groups and fed for a period of 12 weeks: G1: control diet with vitamin D (C/VD+), G2: control diet without vitamin D (C/VD-), G3: high-fat diet with vitamin D (HF/VD+), and G4: high-fat diet without vitamin D (HF/VD-). Sperm function parameters were analyzed by flow cytometry. PMI percentages and O2- levels were not affected by any of the diets. DNA fragmentation was increasing significantly (p<0.05) in the spermatozoa of animals with diets vitamin D deficient (G2) and diet-induced obesity (G4). Our results allow us to point out that diet-induced obesity and VD- produce greater damage in DNA sperm of rats. The use of nutraceuticals containing vitamin D could be reducing the risk of fragmentation of DNA in spermatozoa.

scholarly journals Deficiency of Growth Differentiation Factor 3 Protects against Diet-Induced Obesity by Selectively Acting on White Adipose

2009 ◽  
Vol 23 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Joseph J. Shen ◽  
Lihua Huang ◽  
Liunan Li ◽  
Carolina Jorgez ◽  
Martin M. Matzuk ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Normal Weight ◽  
Metabolic Rates ◽  
Wild Type ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Differentiation Factor ◽  
Tgfβ Superfamily

Growth differentiation factor 3 (GDF3) is a member of the TGFβ superfamily. White adipose is one of the tissues in which Gdf3 is expressed, and it is the only tissue in which expression increases in response to high-fat diet. We generated Gdf3−/− mice, which were indistinguishable from wild-type mice and had normal weight curves on regular diet. However, on high-fat diet Gdf3−/− mice were resistant to the obesity that normally develops in wild-type mice. Herein we investigate the physiological and molecular mechanisms that underlie this protection from diet-induced obesity and demonstrate that GDF3 deficiency selectively affects white adipose through its influence on basal metabolic rates. Our results are consistent with a role for GDF3 in adipose tissue, with consequential effects on energy expenditure that ultimately impact adiposity.

scholarly journals EGCG Prevents High Fat Diet-Induced Changes in Gut Microbiota, Decreases of DNA Strand Breaks, and Changes in Expression and DNA Methylation ofDnmt1andMLH1in C57BL/6J Male Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Marlene Remely ◽  
Franziska Ferk ◽  
Sonja Sterneder ◽  
Tahereh Setayesh ◽  
Sylvia Roth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Damage ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Male Mice ◽  
High Fat ◽  
Methyltransferase 1

Obesity as a multifactorial disorder involves low-grade inflammation, increased reactive oxygen species incidence, gut microbiota aberrations, and epigenetic consequences. Thus, prevention and therapies with epigenetic active antioxidants, (-)-Epigallocatechin-3-gallate (EGCG), are of increasing interest. DNA damage, DNA methylation and gene expression ofDNA methyltransferase 1,interleukin 6, andMutL homologue 1were analyzed in C57BL/6J male mice fed a high-fat diet (HFD) or a control diet (CD) with and without EGCG supplementation. Gut microbiota was analyzed with quantitative real-time polymerase chain reaction. An induction of DNA damage was observed, as a consequence of HFD-feeding, whereas EGCG supplementation decreased DNA damage. HFD-feeding induced a higher inflammatory status. Supplementation reversed these effects, resulting in tissue specific gene expression and methylation patterns ofDNA methyltransferase 1andMutL homologue 1. HFD feeding caused a significant lower bacterial abundance. TheFirmicutes/Bacteroidetesratio is significantly lower in HFD + EGCG but higher in CD + EGCG compared to control groups. The results demonstrate the impact of EGCG on the one hand on gut microbiota which together with dietary components affects host health. On the other hand effects may derive from antioxidative activities as well as epigenetic modifications observed on CpG methylation but also likely to include other epigenetic elements.

260. Effects of diet-induced obesity on ovarian function and female fertility

2005 ◽  
Vol 17 (9) ◽  
pp. 105 ◽  
Author(s):  
C. E. Minge ◽  
B. D. Bennett ◽  
V. Tsagareli ◽  
R. J. Norman ◽  
M. Lane ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Ovarian Function ◽  
Control Diet ◽  
Female Fertility ◽  
Ovulation Rate ◽  
High Fat ◽  
Blastocyst Development ◽  
Diet Induced Obesity

Obesity and its related complications (metabolic syndrome, Type II diabetes and polycystic ovary syndrome) are increasingly associated with female infertility. Our research is focused on understanding how diet-induced obesity, which triggers insulin resistance and symptoms of chronic inflammation, directly impacts ovarian function and female fertility. Female mice were maintained on a “Western style” diet (22% fat, 0.15% cholesterol) or a matched control diet. Body weights were monitored weekly and after 16 weeks fasting insulin levels and glucose tolerance were assessed. Mice were then paired with males and tissues collected on day 1 on pregnancy. Blood samples were taken to determine levels of progesterone, metabolites (glucose, HDL/LDL) and inflammatory cytokines. Tissue weights (fat pads, liver, kidney, spleen, pancreas, ovary and uterus) were recorded and the reproductive tissues were fixed for analysis of histology and gene expression. Zygotes were isolated from the oviduct, cultured in vitro and scored for on-time development and differentially stained to assess blastocyst quality. Indices of ovarian function, including ovulation rate, steroid production and oocyte quality/blastocyst development will then be correlated with degrees of insulin resistance, dyslipidemia and inflammation. Five strains of mice were tested (CBA, Balb/c, C57, SV129 and Swiss) and showed significant differences in susceptibility to diet-induced obesity and insulin resistance. In CBA mice, the first group to be completed, the high fat diet significantly increased body weight, but did not result in overtly impaired glucose tolerance. The number of days to mating was slightly extended compared to mice on the control diet. Interestingly, the high fat diet did not affect ovulation rate but resulted in dramatically impaired blastocyst development. The results of this study will reveal how ovarian folliculogenesis, oocyte competence and ovulation are affected by obesity-induced metabolic changes, which are increasingly affecting women of reproductive age.

Knockout of nephron ATP6AP2 impairs proximal tubule function and prevents high fat diet induced obesity in male mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Silas A Culver ◽  
Safia Akhtar ◽  
Callie Rountree-Jablin ◽  
Susanna R Keller ◽  
Helen P Cathro ◽  
...  
Keyword(s):  
Body Weight ◽  
Proximal Tubule ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Caloric Intake ◽  
Normal Diet ◽  
Male Mice ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Urinary Glucose

Abstract ATP6AP2 expression is increased in the nephron during high fat diet (HFD) and its knockout (ATP6AP2 KO) reduces body weight (WT) in mice. We evaluated the contribution of ATP6AP2 to urinary glucose (UG) and albumin (Ualb) handling during HFD. We hypothesized that nephron ATP6AP2 KO increases UG and Ualb and minimizes HFD-induced obesity. Eight-week old male C57BL/6J mice with inducible nephron specific ATP6AP2 KO and non-induced controls (C) were fed either normal diet (ND, 12% kcal fat) or HFD (45% kcal fat) for 6 months. ATP6AP2 KO mice on ND had 20% (p&lt;0.01) lower WT compared to C. HFD fed mice had 41% (p&lt;0.05) greater WT than ND fed C. In contrast, ATP6AP2 KO abrogated the increase in WT induced by HFD by 40% (p&lt;0.05). Mice on HFD had less caloric intake compared to ND controls (p&lt;0.01). There were no significant differences in metabolic rate between all groups. UG and Ualb was significantly increased in ATP6AP2 KO mice on both ND and HFD. ATP6AP2 KO showed greater levels of proximal tubule apoptosis and histologic evidence of proximal tubule injury. In conclusion, our results demonstrate that nephron specific ATP6AP2 KO is associated with glucosuria and albuminuria, most likely secondary to renal proximal tubule injury and/or dysfunction. Urinary loss of nutrients may have contributed to the reduced WT of knockout mice on ND and lack of WT gain in response to HFD. Future investigation should elucidate the mechanisms by which loss of renal ATP6AP2 causes proximal tubule injury and dysfunction.

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