The Effects of Diet-induced Obesity on the Distribution of System Trace Elements (P24-059-19)

Abstract Objectives Iron (Fe), Copper (Cu), and Manganese (Mn) are essential trace elements that are critical for health and must be maintained in an optimal physiological range. When there is a disturbance of this regulation, such as obesity, pathologies ranging from anemia to neurotoxicity can occur. The objective of this current study is to examine strain and sex differences in the distribution of systemic trace elements due to diet-induced obesity (DIO). We hypothesize that high fat DIO causes significant systemic alterations of Fe, Cu, Mn distributions compared to low fat diet with sex and strain as contributing factors. Methods Beginning at 21 days of age, male and female C57BL/6 J (n = 36) and DBA/2 J (n = 36) mice were fed either a high-fat diet (60% Kcal from fat) or a control diet (10% Kcal from fat) for 16 weeks. Food intake and body mass were measured weekly. At the end of the 16 weeks, blood, liver, and spleen tissues were collected. Fe, Cu, and Mn concentrations were measured using graphite furnace atomic absorption spectroscopy. Results While DIO did not cause any strain or sex differences in hematocrit, differences were detected in all three metals, Mn, Cu, and Fe concentrations in the liver and spleen. Specifically, there was a statistically significant sex by diet interaction on liver Mn concentrations (P = 0.008) and strain by sex interaction on spleen Mn concentrations (P = 0.002). There was a sex by diet and strain by sex interaction on liver Cu concentrations (P = 0.01 and P = 0.006, respectively). A three-way strain, sex, and diet interaction (P = 0.003) was observed for Cu in spleen. There was a strain by sex and strain by diet interaction on liver Fe concentrations (P = 0.031 and P = 0.002, respectively). There was a statistically significant strain, sex, and diet interaction on spleen Fe concentrations (P = 0.0002). The most prominent interactive effects of sex, strain and DIO was observed with liver and spleen Fe concentrations compared to Cu or Mn. For example, male DBA and female C57 mice had greatly reduced Fe in liver and spleen but their opposite sex counterparts were largely unaffected by the impact of DIO. Conclusions Our results expand our previous data by showing strain and sex differences not only in Fe, but Cu and Mn systemic concentrations. For females, the impact of DIO on Fe was more significant in the C57 strain whereas in males the effect of DIO was more significant in the DBA strain. Funding Sources UNCG Health and Human Sciences Research Grant & UNCG Faculty First Award.

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

BioMed Research International ◽

10.1155/2018/5479057 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 5

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.

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High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner

Scientific Reports ◽

10.1038/s41598-020-73166-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

L. Hases ◽

A. Archer ◽

R. Indukuri ◽

M. Birgersson ◽

C. Savva ◽

...

Keyword(s):

Sex Differences ◽

High Fat Diet ◽

Clock Genes ◽

Control Diet ◽

Macrophage Infiltration ◽

Dependent Manner ◽

High Fat ◽

Selective Activation ◽

The Metabolic Syndrome ◽

The Impact

Abstract There is a strong association between obesity and colorectal cancer (CRC), especially in men, whereas estrogen protects against both the metabolic syndrome and CRC. Colon is the first organ to respond to high-fat diet (HFD), and estrogen receptor beta (ERβ) can attenuate CRC development. How estrogen impacts the colon under HFD and related sex differences has, however, not been investigated. To dissect this, mice were fed control diet or HFD for 13 weeks and administered receptor-selective estrogenic ligands for the last three weeks. We recorded impact on metabolism, colon crypt proliferation, macrophage infiltration, and the colon transcriptome. We found clear sex differences in the colon transcriptome and in the impact by HFD and estrogens, including on clock genes. ERα-selective activation reduced body weight and generated systemic effects, whereas ERβ-selective activation had local effects in the colon, attenuating HFD-induced macrophage infiltration and epithelial cell proliferation. We here demonstrate how HFD and estrogens modulate the colon microenvironment in a sex- and ER-specific manner.

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Translational modeling of non-traumatic raised intracranial pressure in rodents; the impact of diet-induced obesity on cephalic hypersensitivity and retinal degeneration

10.1101/2021.08.05.455266 ◽

2021 ◽

Author(s):

Connar Stanley James Westgate ◽

Snorre Malm Hagen ◽

Ida Marchen Egerod Israelsen ◽

Steffen Ellitsgaard Hamann ◽

Rigmor Jensen ◽

...

Keyword(s):

Intracranial Pressure ◽

Control Diet ◽

Disease Model ◽

Fiber Layer ◽

Diet Induced Obesity ◽

The Impact ◽

First Time ◽

Novel Model ◽

Icp Recording ◽

Translational Modeling

Elevated intracranial pressure (ICP) is a feature of critical cerebral disorders. Obesity has been linked to raised ICP, and especially to disorders such as idiopathic intracranial pressure (IIH). We aimed to explore the impact of diet-induced obesity (DIO) on ICP, cephalic sensitivity and structural retinal changes with the dual goal of developing a disease model for non-traumatic raised ICP and IIH. Rats were fed high-fat diet or matched control diet. To assess pain sensitivity, Von Frey and light/dark box testing were performed. Dual energy x-ray absorptiometry scanning was used to measure body composition. Optic nerve head and retinal structures were evaluated using optical coherence tomography. Intraocular pressure was assessed. Rats were then implanted with telemetric device for continuous ICP recording. At the end, eye histology and molecular analysis on choroid plexus (CP) and trigeminal ganglion (TG) were performed. The DIO rats had double the abdominal fat mass. ICP was 55% higher in obese rats (p=0.003). Altered pain thresholds were found in DIO rats as denoted by a lower periorbital threshold (p=0.0002). Expression of Calca and Trpv1 was elevated in TG. Furthermore, a peripapillary retinal nerve fiber layer swelling (p=0.0026) with subsequent neuroretinal degeneration p=0.02) was detected in DIO rats. There was a trend to increased expression of AQP1 and NKCC1 at CP. This study demonstrates for the first time that DIO leads to raised ICP, with clinically relevant sequalae. Our novel model for non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP and IIH.

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The Impact of DJOS Surgery, a High Fat Diet and a Control Diet on the Enzymes of Glucose Metabolism in the Liver and Muscles of Sprague-Dawley Rats

Frontiers in Physiology ◽

10.3389/fphys.2019.00571 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Dominika Stygar ◽

Dorian Andrare ◽

Barbara Bażanów ◽

Elżbieta Chełmecka ◽

Tomasz Sawczyn ◽

...

Keyword(s):

Glucose Metabolism ◽

High Fat Diet ◽

Control Diet ◽

Sprague Dawley ◽

High Fat ◽

Sprague Dawley Rats ◽

The Impact

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SIRT6 in mouse spermatogenesis is modulated by diet-induced obesity

Reproduction Fertility and Development ◽

10.1071/rd10326 ◽

2011 ◽

Vol 23 (7) ◽

pp. 929 ◽

Cited By ~ 64

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.

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Mass Spectrometry-Based Metabolomic and Lipidomic Analysis of the Effect of High Fat/High Sugar Diet and GreenshellTM Mussel Feeding on Plasma of Ovariectomized Rats

Metabolites ◽

10.3390/metabo11110754 ◽

2021 ◽

Vol 11 (11) ◽

pp. 754

Author(s):

Maryam Abshirini ◽

Diana Cabrera ◽

Karl Fraser ◽

Parkpoom Siriarchavatana ◽

Frances M. Wolber ◽

...

Keyword(s):

Mass Spectrometry ◽

Control Diet ◽

Ovariectomized Rats ◽

High Fat ◽

High Sugar ◽

Ovx Rats ◽

Lipid Species ◽

Metabolite Profiles ◽

The Impact ◽

Potential Biomarkers

This study aimed to examine the changes in lipid and metabolite profiles of ovariectomized (OVX) rats with diet-induced metabolic syndrome-associated osteoarthritis (MetOA) after supplementation with greenshell mussel (GSM) using an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach. Ninety-six rats were fed with one of four diets: control, control supplemented with GSM + GSM, high fat/high sugar (HFHS), or high fat/high sugar enriched with GSM (HFHS + GSM). After 8 weeks on experimental diets, half of the rats in each group underwent OVX and the other half were sham operated. After being fed for an additional 28 weeks, blood samples were collected for the metabolomics analysis. Lipid and polar metabolites were extracted from plasma and analysed by LC-MS. We identified 29 lipid species from four lipid subclasses (phosphatidylcholine, lysophosphatidylcholine, diacylglycerol, and triacylglycerol) and a set of eight metabolites involved in amino acid metabolism (serine, threonine, lysine, valine, histidine, pipecolic acid, 3-methylcytidine, and cholic acid) as potential biomarkers for the effect of HFHS diet and GSM supplementation. GSM incorporation more specifically in the control diet generated significant alterations in the levels of several lipids and metabolites. Further studies are required to validate these findings that identify potential biomarkers to follow OA progression and to monitor the impact of GSM supplementation.

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Cancer Stem Cell Enrichment and Metabolic Substrate Adaptability are Driven by Hydrogen Sulfide Suppression in Glioblastoma

10.1101/2020.03.08.982116 ◽

2020 ◽

Author(s):

Daniel J. Silver ◽

Gustavo A. Roversi ◽

Nazmin Bithi ◽

Chase K. A. Neumann ◽

Katie M. Troike ◽

...

Keyword(s):

Stem Cell ◽

Hydrogen Sulfide ◽

Cancer Stem Cell ◽

High Fat Diet ◽

Control Diet ◽

Chemotherapy Resistance ◽

Cellular Metabolism ◽

Protein S ◽

High Fat ◽

The Impact

AbstractGlioblastoma (GBM) remains among the deadliest of human malignancies. The emergence of the cancer stem cell (CSC) phenotype represents a major challenge to disease management and durable treatment response. The extrinsic, environmental, and lifestyle factors that result in CSC enrichment are not well understood. The CSC state endows cells with a fluid metabolic profile, enabling the utilization of multiple nutrient sources. Therefore, to test the impact of diet on CSC enrichment, we evaluated disease progression in tumor-bearing mice fed an obesity-inducing high-fat diet (HFD) versus an energy-balanced, low-fat control diet. HFD consumption resulted in hyper-aggressive disease that was accompanied by CSC enrichment and shortened survival. HFD consumption also drove intracerebral accumulation of saturated fats, which in turn inhibited the production and signaling of the gasotransmitter hydrogen sulfide (H2S). H2S is an endogenously produced bio-active metabolite derived from sulfur amino acid catabolism. It functions principally through protein S-sulfhydration and regulates a variety of programs including mitochondrial bioenergetics and cellular metabolism. Inhibition of H2S synthesis resulted in increased proliferation and chemotherapy resistance, whereas treatment with H2S donors led to cytotoxicity and death of cultured GBM cells. Compared to non-cancerous controls, patient GBM specimens were reduced in overall protein S-sulfhydration, which was primarily lost from proteins regulating cellular metabolism. These findings support the hypothesis that diet-regulated H2S signaling serves to suppress GBM by restricting metabolic adaptability, while its loss triggers CSC enrichment and disease acceleration. Interventions augmenting H2S bioavailability concurrent with GBM standard of care may improve outcomes for GBM patients.One Sentence SummaryConsumption of a high-fat diet (HFD) accelerates glioblastoma (GBM) by inhibiting the production and signaling of the tumor-suppressive metabolite hydrogen sulfide (H2S).

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Obesity is associated with heavy menstruation that may be due to delayed endometrial repair

Journal of Endocrinology ◽

10.1530/joe-20-0446 ◽

2021 ◽

Vol 249 (2) ◽

pp. 71-82

Author(s):

Jane J Reavey ◽

Catherine Walker ◽

Alison A Murray ◽

Savita Brito-Mutunayagam ◽

Sheona Sweeney ◽

...

Keyword(s):

Blood Loss ◽

High Fat Diet ◽

Statistical Significance ◽

Surrogate Marker ◽

Menstrual Blood ◽

Menstrual Blood Loss ◽

High Fat ◽

Mean Values ◽

Diet Induced Obesity ◽

The Impact

Heavy menstrual bleeding is common and debilitating but the causes remain ill defined. Rates of obesity in women are increasing and its impact on menstrual blood loss (MBL) is unknown. Therefore, we quantified BMI and MBL in women not taking hormones and with regular menstrual cycles and revealed a positive correlation. In a mouse model of simulated menstruation, diet-induced obesity also resulted in delayed endometrial repair, a surrogate marker for MBL. BrdU staining of mouse uterine tissue revealed decreased proliferation during menstruation in the luminal epithelium of mice on a high-fat diet. Menstruation is known to initiate local endometrial inflammation and endometrial hypoxia; hence, the impact of body weight on these processes was investigated. A panel of hypoxia-regulated genes (VEGF, ADM, LDHA, SLC2A1) showed consistently higher mean values in the endometrium of women with obesity and in uteri of mice with increased weight vs normal controls, although statistical significance was not reached. The inflammatory mediators, Tnf and Il6 were significantly increased in the uterus of mice on a high-fat diet, consistent with a pro-inflammatory local endometrial environment in these mice. In conclusion, obesity was associated with increased MBL in women. Mice given a high-fat diet had delayed endometrial repair at menstruation and provided a model in which to study the influence of obesity on menstrual physiology. Our results indicate that obesity results in a more pro-inflammatory local endometrial environment at menstruation, which may delay endometrial repair and increase menstrual blood loss.

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

Reproduction Fertility and Development ◽

10.1071/srb05abs260 ◽

2005 ◽

Vol 17 (9) ◽

pp. 105 ◽

Cited By ~ 1

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.

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