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

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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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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The Effect of High-Fat Diet-Induced Obesity on the Expression of Nutrient Chemosensors in the Mouse Stomach and the Gastric Ghrelin Cell

Nutrients ◽

10.3390/nu12092493 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2493

Author(s):

Maria Nunez-Salces ◽

Hui Li ◽

Stewart Christie ◽

Amanda J. Page

Keyword(s):

High Fat Diet ◽

Primary Source ◽

Nutrient Sensing ◽

Mrna Levels ◽

Limited Information ◽

High Fat ◽

Diet Induced Obesity ◽

Standard Laboratory Diet ◽

Ghrelin Secretion ◽

The Impact

The stomach is the primary source of the orexigenic and adiposity-promoting hormone, ghrelin. There is emerging evidence on the nutrient-mediated modulation of gastric ghrelin secretion. However, limited information is available on gastric nutrient-sensing mechanisms in high-fat diet (HFD)-induced obesity. This study investigated the impact of HFD-induced obesity on the expression of nutrient chemosensors in mouse stomach, particularly ghrelin cells. Male C57BL/6 mice were fed either a standard laboratory diet (SLD) or HFD for 12 weeks. The expression of ghrelin, enzymes involved in ghrelin production (PC1/3, GOAT) and nutrient chemosensors (CD36, FFAR2&4, GPR93, CaSR, mGluR4 and T1R3) was determined by quantitative RT-PCR in the mouse corpus and antrum. Immunohistochemistry assessed the protein expression of CaSR and ghrelin in the corpus and antrum. Antral mRNA levels of CaSR and PC1/3 were increased in HFD compared to SLD mice, while mRNA levels of all other nutrient chemosensors examined remained unchanged. CaSR immunolabelling was observed in the gastric antrum only. Nearly 80% of antral ghrelin cells expressed CaSR, with a similar cell density and co-expression in SLD and HFD mice. In conclusion, HFD-induced obesity increased CaSR mRNA expression in mouse antrum. However, the high antral co-expression of CaSR and ghrelin was unaltered in HFD compared to SLD mice.

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Depletion of the gut microbiota differentially affects the impact of whey protein on high‐fat diet‐induced obesity and intestinal permeability

Physiological Reports ◽

10.14814/phy2.14867 ◽

2021 ◽

Vol 9 (11) ◽

Author(s):

Serena Boscaini ◽

Raul Cabrera‐Rubio ◽

Anna Golubeva ◽

Oleksandr Nychyk ◽

Christine Fülling ◽

...

Keyword(s):

Gut Microbiota ◽

Whey Protein ◽

Intestinal Permeability ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity ◽

The Impact

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Mice Lacking the Thyroid Hormone Receptor-α Gene Spend More Energy in Thermogenesis, Burn More Fat, and Are Less Sensitive to High-Fat Diet-Induced Obesity

Endocrinology ◽

10.1210/en.2008-0718 ◽

2008 ◽

Vol 149 (12) ◽

pp. 6471-6486 ◽

Cited By ~ 49

Author(s):

Paula Pelletier ◽

Karine Gauthier ◽

Olga Sideleva ◽

Jacques Samarut ◽

J. Enrique Silva

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Respiratory Quotient ◽

Thyroid Hormone Receptor ◽

Fuel Efficiency ◽

Tissue Type ◽

High Fat ◽

Diet Induced Obesity ◽

Brown Adipose ◽

The Impact

Unable to activate brown adipose tissue (BAT) thermogenesis, αT3-receptor-deficient mice (Thra-0/0) are cold intolerant. Our objective was to investigate the impact on energy economy and mechanisms of the alternate facultative thermogenesis developed. Energy expenditure (oxygen and food consumption) is elevated in Thra-0/0 mice reared at room temperature. Such difference disappears at thermoneutrality (30 C) and expands as ambient temperature becomes colder (P < 0.001). Despite eating more, Thra-0/0 are leaner than wild-type (WT) mice (P < 0.01), whereas these, whether on chow or high-fat diet, gained more weight (g/d: 0.12 ± 0.002 vs. 0.08 ± 0.002 and 0.25 ± 0.005 vs. 0.17 ± 0.005, respectively) and adiposity than Thra-0/0 mice (P < 0.001). The respiratory quotient was lower in Thra-0/0 than WT mice (P < 0.001), after feeding or fasted, on chow or high-fat diet, indicating a preference for fat as fuel, which was associated with increased lipoprotein lipase (LPL) expression in skeletal muscle of Thra-0/0 mice but with no differences in gene expression in white adipose tissue. Type-2 deiodinase (D2) was increased in BAT and aerobic muscle of Thra-0/0 mice. This and liver D1 were increased by a high-fat diet in both genotypes, as also were serum T3 and T3/T4 ratio, but more in Thra-0/0 than WT mice (P < 0.001). Remarkably, when studied at thermoneutrality, genotype differences in weight and adiposity gain, respiratory quotient, D2, and LPL disappeared. Thus, disruption of BAT thermogenesis in Thra-0/0 mice activates an alternate facultative thermogenesis that is more energy demanding and associated with reduced fuel efficiency, leanness, increased capacity to oxidize fat, and relative resistance to diet-induced obesity, in all of which muscle LPL and deiodinases play a key role.

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Acute vs chronic exposure to high fat diet leads to distinct regulation of PKA

Journal of Molecular Endocrinology ◽

10.1530/jme-16-0188 ◽

2017 ◽

Vol 59 (1) ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Edra London ◽

Maria Nesterova ◽

Constantine A Stratakis

Keyword(s):

High Fat Diet ◽

Energy Homeostasis ◽

Critical Role ◽

Metabolic Dysfunction ◽

High Fat ◽

Diet Induced Obesity ◽

Subunit Expression ◽

Peripheral Effect ◽

Dependent Protein ◽

The Impact

The cAMP-dependent protein kinase (PKA) is an essential regulator of lipid and glucose metabolism that plays a critical role in energy homeostasis. The impact of diet on PKA signaling has not been defined, although perturbations in individual PKA subunits are associated with changes in adiposity, physical activity and energy intake in mice and humans. We hypothesized that a high fat diet (HFD) would elicit peripheral and central alterations in the PKA system that would differ depending on length of exposure to HFD; these differences could protect against or promote diet-induced obesity (DIO). 12-week-old C57Bl/6J mice were randomly assigned to a regular diet or HFD and weighed weekly throughout the feeding studies (4 days, 14 weeks; respectively), and during killing. PKA activity and subunit expression were measured in liver, gonadal adipose tissue (AT) and brain. Acute HFD-feeding suppressed basal hepatic PKA activity. In contrast, hepatic and hypothalamic PKA activities were significantly increased after chronic HFD-feeding. Changes in AT were more subtle, and overall, altered PKA regulation in response to chronic HFD exposure was more profound in female mice. The suppression of hepatic PKA activity after 4 day HFD-feeding was indicative of a protective peripheral effect against obesity in the context of overnutrition. In response to chronic HFD-feeding, and with the development of DIO, dysregulated hepatic and hypothalamic PKA signaling was a signature of obesity that is likely to promote further metabolic dysfunction in mice.

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Abstract P238: High Fat Diet-induced Obesity Disrupts Vascular Homeostasis in Both Kidney and Retina: Role of Epoxyeicosatrienoic Acids

Hypertension ◽

10.1161/hyp.66.suppl_1.p238 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Ahmed A Elmarakby ◽

Mohamed A Katary ◽

Islam N Mohamed ◽

Azza B El-Remessy

Keyword(s):

Endothelial Function ◽

High Fat Diet ◽

Microvascular Complications ◽

Vascular Inflammation ◽

Epoxyeicosatrienoic Acids ◽

Inflammasome Activation ◽

Obese Mice ◽

High Fat ◽

Diet Induced Obesity ◽

The Impact

Obesity-induced vascular inflammation is considered an early and common pathological change for the development of microvascular complications including retinopathy and nephropathy. We have previously demonstrated that obesity down-regulated renal cytochrome P450 epoxygenase and decreased epoxyeicosatrienoic acids (EETs) levels in kidney as well as triggered retinal expression of the pro-inflammatory thioredoxin interacting protein (TXNIP) that coincided with vascular inflammation. The aim of this work is to examine the impact of obesity-induced reduction in EETs levels on TXNIP-inflammasome activation. Because EETs are quickly hydrolyzed by the soluble epoxide hydrolase (sEH) enzyme to inactive metabolites, we use sEH gene deleted mice (Ephx2 -/-) as a model with high EETs levels. WT and Ephx2 -/- were fed normal (14 % fat) or high fat diet (HFD, 60 % fat) for three months. HFD treatment down-regulated cyp2c44, the main epoxygenase for EETs production, and decreased EETs levels in kidney of obese mice and these changes were associated with podocyte loss and increased podocalyxin excretion as markers of glomerular injury. Although HFD treatment decreased EETs levels in Ephx2 -/- mice, it remained significantly higher than obese WT mice. HFD impaired endothelial function and induced TXNIP-inflammasome activation evident by increases in NOD-like receptor-3 (NLRP3) and interleukin-1β (IL-1β) in both retina and kidney. In parallel, HFD also increased leukostasis, retinal vascular permeability and development of acellular capillary, hall mark of ischemia in WT but not in TXNIP-/-. Restoring EETs levels in Ephx2 -/- mice improved endothelial function and was associated with decreased TXNIP-mediated inflammasome activation in the kidney of obese mice. Our data suggest that diet-induced obesity causes homeostatic imbalance by down-regulation of the anti-inflammatory epoxygenase/EETs levels and increasing the inflammatory TXNIP expression resulting in vascular injury in both retina and kidney.

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Role of skeletal muscle autophagy in high-fat-diet–induced obesity and exercise

Nutrition Reviews ◽

10.1093/nutrit/nuz044 ◽

2019 ◽

Vol 78 (1) ◽

pp. 56-64

Author(s):

Adrienne R Herrenbruck ◽

Lance M Bollinger

Keyword(s):

Skeletal Muscle ◽

High Fat Diet ◽

Control Mechanism ◽

Degradation Pathway ◽

The Body ◽

High Fat ◽

Diet Induced Obesity ◽

Quality Control Mechanism ◽

The Impact

Abstract Autophagy is a complex degradation pathway responsible for clearing damaged and dysfunctional organelles. High-fat-diet–induced obesity has been shown to alter autophagy throughout the body in a tissue-specific manner. The impact of obesity on skeletal muscle autophagy has yet to be elucidated. This review examines the impact of high-fat-diet–induced obesity and exercise on skeletal muscle autophagy. Better understanding this major quality control mechanism may help develop novel therapies to combat high-fat-diet–induced obesity comorbidities.

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The Interaction between Mitochondrial Oxidative Stress and Gut Microbiota in the Cardiometabolic Consequences in Diet-Induced Obese Rats

Antioxidants ◽

10.3390/antiox9070640 ◽

2020 ◽

Vol 9 (7) ◽

pp. 640

Author(s):

Adriana Ortega-Hernández ◽

Ernesto Martínez-Martínez ◽

Ruben Gómez-Gordo ◽

Natalia López-Andrés ◽

Amaya Fernández-Celis ◽

...

Keyword(s):

Oxidative Stress ◽

Gut Microbiota ◽

High Fat Diet ◽

Cardiac Fibrosis ◽

High Fat ◽

Mitochondrial Oxidative Stress ◽

Colonic Mucin ◽

Diet Induced Obesity ◽

Male Wistar Rats ◽

The Impact

Background: The objective of this study is to determine the role of mitochondrial oxidative stress in the dysbiosis associated with a high fat diet in rats. In addition, the impact of gut microbiota (GM) in the cardiometabolic consequences of diet-induced obesity in rats has been evaluated. Methods: Male Wistar rats were fed either a high fat diet (HFD) or a control (CT) one for 6 weeks. At the third week, one-half of the animals of each group were treated with the mitochondrial antioxidant MitoTempo (MT; 0.7 mgKg−1day−1 i.p). Results: Animals fed an HFD showed a lower microbiota evenness and diversity in comparison to CT rats. This dysbiosis is characterized by a decrease in Firmicutes/Bacteroidetes ratio and relevant changes at family and genera compared with the CT group. This was accompanied by a reduction in colonic mucin-secreting goblet cells. These changes were reversed by MT treatment. The abundance of certain genera could also be relevant in the metabolic consequences of obesity, as well as in the occurrence of cardiac fibrosis associated with obesity. Conclusions: These results support an interaction between GM and mitochondrial oxidative stress and its relation with development of cardiac fibrosis, suggesting new approaches in the management of obesity-related cardiometabolic consequences.

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