High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner
Ontology highlight
ABSTRACT:
SUBMITTER: Hases L
PROVIDER: S-EPMC7527340 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Obesity is often associated with increased pain, but little is known about the effects of obesity and diet on postoperative pain. In this study, effects of diet and obesity were examined in the paw incision model, a preclinical model of postoperative pain. Long-Evans rats were fed high-fat diet (40% calories from butter fat) or low-fat normal chow. Male rats fed high-fat diet starting 6 weeks before incision (a diet previously shown to induce markers of obesity) had prolonged mechanical hypersensitivity and an overall increase in spontaneous pain in response to paw incision, compared with normal chow controls. Diet effects in females were minor. Removing high-fat diet for 2 weeks before incision reversed the diet effects on pain behaviors, although this was not enough time to reverse high-fat diet-induced weight gain. A shorter (1 week) exposure to high-fat diet before incision also increased pain behaviors in males, albeit to a lesser degree. The 6-week high-fat diet increased macrophage density as examined immunohistochemically in lumbar dorsal root ganglion even before paw incision, especially in males, and sensitized responses of peritoneal macrophages to lipopolysaccharide stimuli in vitro. The nerve regeneration marker growth-associated protein 43 (GAP43) in skin near the incision (day 4) was higher in the high-fat diet group, and wound healing was delayed. In summary, high-fat diet increased postoperative pain particularly in males, but some diet effects did not depend on weight gain. Even short-term dietary manipulations, that do not affect obesity, may enhance postoperative pain.
| S-EPMC6095797 | biostudies-literature
Project description:Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC), but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-? estradiol (E2) pellet and/or high-fat diet (HFD) for 12 weeks to mimic sustained estrogen stimulation and insulin resistance. Histomorphologically, we found that both E2 and E2?+?HFD groups showed markedly enlarged uterus and increased number of endometrial glands. The endometrium samples were collected for microarray assay. GO and KEGG analysis showed that genes regulated by E2 and/or HFD are mainly responsible for immune response, inflammatory response and metabolic pathways. Further IPA analysis demonstrated that the acute phase response signaling, NF-?B signaling, leukocyte extravasation signaling, PPAR signaling and LXR/RXR activation pathways are mainly involved in the pathways above. In addition, the genes modulated reciprocally by E2 and/or HFD were also analyzed, and their crosstalk mainly focuses on enhancing one another's activity. The combination analysis of microarray data and TCGA database provided potential diagnostic or therapeutic targets for EC. Further validation was performed in mice endometrium and human EC cell lines. In conclusion, this study unraveled the endometrial transcriptome profile alterations affected by E2 and/or HFD that may disturb endometrial homeostasis and contribute to the development of endometrial hyperplasia.
| S-EPMC5744625 | biostudies-literature
Project description:Characterization of endocrine-cell functions and associated molecular signatures in diabetes is crucial to better understand why and by which mechanisms alpha and beta cells cause and perpetuate metabolic abnormalities. The now recognized role of glucagon in diabetes control is a major incentive to have a better understanding of dysfunctional alpha cells. To characterize molecular alterations of alpha cells in diabetes, we analyzed alpha-cell transcriptome from control and diabetic mice using diet-induced obesity model. To this aim, we quantified the expression levels of total mRNAs from sorted alpha and beta cells of low-fat and high-fat diet-treated mice through RNAseq experiments, using a transgenic mouse strain allowing collections of pancreatic alpha- and beta-cells after 16 weeks of diet. We now report that pancreatic alpha cells from obese hyperglycemic mice displayed minor variations of their transcriptome compared to controls. Depending on analyses, we identified 11 to 39 differentially expressed genes including non-alpha cell markers mainly due to minor cell contamination during purification process. From these analyses, we identified three new target genes altered in diabetic alpha cells and potently involved in cellular stress and exocytosis (Upk3a, Adcy1 and Dpp6). By contrast, analysis of the beta-cell transcriptome from control and diabetic mice revealed major alterations of specific genes coding for proteins involved in proliferation and secretion. We conclude that alpha cell transcriptome is less reactive to HFD diet compared to beta cells and display adaptations to cellular stress and exocytosis.
| S-EPMC6407777 | biostudies-literature
Project description:Ghrelin is a potent orexigenic hormone that likely impacts eating via several mechanisms. Here, we hypothesized that ghrelin can regulate extra homeostatic, hedonic aspects of eating behavior.In the current study, we assessed the effects of different pharmacological, physiological, and genetic models of increased ghrelin and/or ghrelin-signaling blockade on two classic behavioral tests of reward behavior: conditioned place preference (CPP) and operant conditioning.Using both CPP and operant conditioning, we found that ghrelin enhanced the rewarding value of high-fat diet (HFD) when administered to ad lib-fed mice. Conversely, wild-type mice treated with ghrelin receptor antagonist and ghrelin receptor-null mice both failed to show CPP to HFD normally observed under calorie restriction. Interestingly, neither pharmacologic nor genetic blockade of ghrelin signaling inhibited the body weight homeostasis-related, compensatory hyperphagia associated with chronic calorie restriction. Also, ghrelin's effects on HFD reward were blocked in orexin-deficient mice and wild-type mice treated with an orexin 1 receptor antagonist.Our results demonstrate an obligatory role for ghrelin in certain rewarding aspects of eating that is separate from eating associated with body weight homeostasis and that requires the presence of intact orexin signaling.
| S-EPMC2854245 | biostudies-literature
Project description:Obesity is a prevalent prothrombotic risk factor marked by enhanced fibrin formation and suppressed fibrinolysis. Fibrin both promotes thrombotic events and drives obesity pathophysiology, but a lack of essential analytical tools has left fibrinolytic mechanisms affected by obesity poorly defined. Using a plasmin-specific fluorogenic substrate, we developed a plasmin generation (PG) assay for mouse plasma that is sensitive to tissue plasminogen activator, α2-antiplasmin, active plasminogen activator inhibitor (PAI-1), and fibrin formation, but not fibrin crosslinking. Compared with plasmas from mice fed a control diet, plasmas from mice fed a high-fat diet (HFD) showed delayed PG and reduced PG velocity. Concurrent to impaired PG, HFD also enhanced thrombin generation (TG). The collective impact of abnormal TG and PG in HFD-fed mice produced normal fibrin formation kinetics but delayed fibrinolysis. Functional and proteomic analyses determined that delayed PG in HFD-fed mice was not due to altered levels of plasminogen, α2-antiplasmin, or fibrinogen. Changes in PG were also not explained by elevated PAI-1 because active PAI-1 concentrations required to inhibit the PG assay were 100-fold higher than circulating concentrations in mice. HFD-fed mice had increased circulating thrombomodulin, and inhibiting thrombomodulin or thrombin-activatable fibrinolysis inhibitor (TAFI) normalized PG, revealing a thrombomodulin- and TAFI-dependent antifibrinolytic mechanism. Integrating kinetic parameters to calculate the metric of TG/PG ratio revealed a quantifiable net shift toward a prothrombotic phenotype in HFD-fed mice. Integrating TG and PG measurements may define a prothrombotic risk factor in diet-induced obesity.
| S-EPMC7205812 | biostudies-literature
Project description:Epidemiology studies indicate that consumption of high-fat diet (HFD) is directly associated with the development of colorectal cancer (CRC). However, the exact component in HFD and the mechanism underlying its effect on CRC growth remained unclear. Our study shows that HFD feeding increases β2AR expression in the xenograft tissues of CRC-bearing mouse model; the elevated β2AR expression is reduced when HFD is replaced by control diet, which strongly suggests an association between HFD feeding and β2AR expression in CRC. HFD feeding increases palmitic acid and stearic acid levels in CRC; however, only palmitic acid increases β2AR expression, which is dependent upon Sp1. β2AR plays the dominant role in promoting CRC cell proliferation among all the β-AR subtypes. More importantly, knockout of β2AR or knockdown of Sp1 abolishes the palmitic acid increased CRC cell proliferation, suggesting palmitic acid increases CRC cell proliferation in β2AR-dependent manner. HFD or palmitic acid-rich diet (PAD) also fails to increase the tumor growth in xenograft mouse models bearing β2AR-knockout CRC cells. β2AR promotes CRC growth by increasing the phosphorylation of HSL at the residue S552. The phosphorylated and activated HSL (S552) changes the metabolic phenotype of CRC and increases energy production, which promotes CRC growth. Our study has revealed the unique tumorigenic properties of palmitic acid in promoting CRC growth, and have delineated the underlying mechanism of action. We are also the first to report the linkage between HFD feeding and β-adrenergic signaling pathway in relation to CRC growth.
| S-EPMC6763436 | biostudies-literature
Project description:Lactation is a critical period during which maternal sub- or over-nutrition affect milk composition and offspring development that can have lasting health effects. The consequences of moderate high-fat, high-simple carbohydrate diet (WD) consumption by rat dams, during gestation and lactation, on milk composition and offspring blood lipidome and its growth, at weaning, were investigated by using a comprehensive lipidomic study on mass-spectrometric platform combined to targeted fatty- and free amino-acids analysis. This holistic approach allowed clear-cut differences in mature milk-lipidomic signature according to maternal diet with a similar content of protein, lactose and leptin. The lower WD-milk content in total fat and triglycerides (TGs), particularly in TGs-with saturated medium-chain, and higher levels in both sphingolipid (SL) and TG species with unsaturated long-chain were associated to a specific offspring blood-lipidome with decreased levels in TGs-containing saturated fatty acid (FA). The sexual-dimorphism in the FA-distribution in TG (higher TGs-rich in oleic and linoleic acids, specifically in males) and SL species (increased levels in very long-chain ceramides, specifically in females) could be associated with some differences that we observed between males and females like a higher total body weight gain in females and an increased preference for fatty taste in males upon weaning.
| S-EPMC7432416 | biostudies-literature
Project description:Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal high LA (HLA) diet on plasma FA composition, plasma and hepatic lipids and genes involved in lipid metabolism in the liver of adult offspring. Female rats were fed with low LA (LLA; 1.44% LA) or HLA (6.21% LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed either LLA or HLA diets and sacrificed at PN180. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. Maternal HLA diet increased circulating leptin in female offspring, but not in males. Maternal HLA diet decreased circulating adiponectin in males. Postnatal HLA diet significantly decreased aspartate transaminase (AST) in females and downregulated total cholesterol, HDL-cholesterol and triglycerides in the plasma of males. Maternal HLA diet downregulated the hepatic mRNA expression of Hmgcr in both male and female offspring and decreased the hepatic mRNA expression of Cpt1a and Acox1 in females. Both maternal and postnatal HLA diet decreased hepatic mRNA expression of Cyp27a1 in females. Postnatal diet significantly altered circulating fatty acid concentrations, with sex-specific differences in genes that control lipid metabolism in the adult offspring following exposure to high LA diet in utero.
| S-EPMC7999727 | biostudies-literature
Project description:Gut microbiota is involved in metabolic disorders. However, microbiome-based therapeutic interventions are not always effective, which might be due to interference of the host factors. Here, we first identified a strong positive correlation between OPN levels and BMI in humans. Next, we confirmed that OPN could aggravate high-fat diet induced metabolic disorders in mice. Importantly, we found that fecal microbiota transplantation from OPN-deficient mice significantly alleviated metabolic disorders in WT mice. OPN directly induces remodeling of the gut microbiota both in vitro and in vivo. These findings indicate that OPN could contribute to metabolic disorders by inducing an alteration of gut microbiota. OPN regulated the relative abundance of Lactobacillus by decreasing the adhesion of Lactobacillus to intestinal epithelial cells through Notch signaling pathway. These data identify OPN may serve as a potential pharmaceutical target for weight control and metabolic disorders treatment.
2022-10-26 | GSE216386 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) represents a public health issue, due to its prevalence and association with other cardiometabolic diseases. Growing evidence suggests that NAFLD alters the production of hepatokines, which, in turn, influence several metabolic processes. Despite accumulating evidence on the major role of estrogen signaling in the sexually dimorphic nature of NAFLD, dependency of hepatokine expression on sex and estrogens has been poorly investigated. Through in vitro and in vivo analysis, we determined the extent to which hepatokines, known to be altered in NAFLD, can be regulated, in a sex-specific fashion, under different hormonal and nutritional conditions. Our study identified four hepatokines that better recapitulate sex and estrogen dependency. Among them, adropin resulted as one that displays a sex-specific and estrogen receptor alpha (ERα)-dependent regulation in the liver of mice under an excess of dietary lipids (high-fat diet, HFD). Under HFD conditions, the hepatic induction of adropin negatively correlates with the expression of lipogenic genes and with fatty liver in female mice, an effect that depends upon hepatic ERα. Our findings support the idea that ERα-mediated induction of adropin might represent a potential approach to limit or prevent NAFLD.
| S-EPMC9416503 | biostudies-literature