Menopausal status and hepatic steatosis in a general female population

Völzke, Henry; Schwarz, Sabine; Baumeister, Sebastian E.; Wallaschofski, Henri; Schwahn, Christian; Grabe, Hans J.; Kohlmann, Thomas; John, Ulrich; Dören, Martina

doi:10.1136/gut.2006.115345

Cited by 130 publications

(99 citation statements)

References 11 publications

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“…Ovariectomized (OVX) rats, as well as aromatase, and estrogen receptor knockout mice develop nonalcoholic fatty liver disease (NAFLD), which is characterized by triglyceride accumulation in hepatocytes (hepatic steatosis) (Lemieux et al 2005), one of the most frequent causes of abnormal liver function (Angulo 2002;Browning and Horton 2004). In a recent study that included over 800 women aged 40-59 years, it was confirmed that the menopausal status was indeed associated with hepatic steatosis (Volzke et al 2007). Thus, it is important to investigate interventions that may prevent or attenuate the accumulation of lipids into liver with a decrease in plasma estrogens.…”

Section: Introductionmentioning

confidence: 90%

Resistance training restores the gene expression of molecules related to fat oxidation and lipogenesis in the liver of ovariectomized rats

et al. 2011

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Decreased levels of estrogen are associated with hepatic steatosis (HS), through changes in gene expression of molecules related to fat oxidation and lipogenesis. Both resistance training (RT) and endurance training (ET) prevent HS in ovariectomized (Ovx) rats. However, the molecular events associated with this process were only investigated for ET, but not for RT. Thus, the aim of this study was to investigate the effects of Ovx and RT on the gene expression of molecules related to fat oxidation and lipogenesis in the liver of rats. Sprague-Dawley adult female rats were grouped into four (n = 6 per group): sham-operated sedentary (Sham-Sed); Ovx sedentary (Ovx-Sed); sham-Rt and Ovx-Rt. A 10-week RT period, during which the animals climbed a 1.1-m vertical ladder with weights attached to their tails, was used. The sessions were performed three times a week, with 4-9 climbs and 8-12 dynamic movements per climb. Gene expression was analyzed by RT-PCR by the ∆∆Ct method. The estrogen deficiency associated with ovariectomy decreased the gene expression of molecules related to fat oxidation, carnitine palmitoyltransferase I (53%) and β-hydroxyacyl-CoA dehydrogenase (27%), and increased molecules related to lipogenesis, sterol regulatory element-binding protein-1c (106%), acetyl-CoA carboxylase (ACC) (72%) and stearoyl CoA desaturase-1 (109%). With the exception of ACC, the ovariectomy-induced changes in the expression of these molecules were restored by RT. The present results indicate that RT has important effects on the prevention of HS in Ovx animals, through changes in gene expression of molecules related to hepatic lipid metabolism.

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Section: Introductionmentioning

confidence: 90%

Resistance training restores the gene expression of molecules related to fat oxidation and lipogenesis in the liver of ovariectomized rats

et al. 2011

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“…Our study suggests that the tetradian activity of liver ERα is important in readying the receptor to adjust to the changes of energy requirements in relation to the reproductive stage. These findings are particularly relevant for the understanding of the etiology of metabolic disorders and hepatic lipid metabolism associated with impaired ovarian functions (e.g., polycystic ovary syndrome or the cessation of the reproductive cycle) (37), indicating that selective ER modulators (SERMs) may reinstate ER oscillatory activity. This suggests a revision of current rationales for treating postmenopause problems, taking into account the periodic nature of ER signaling to ensure the more efficacious use of estrogens.…”

Section: Discussionmentioning

confidence: 99%

Tetradian oscillation of estrogen receptor α is necessary to prevent liver lipid deposition

Villa

Torre²,

Stell³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

117

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In the liver of female mice, the transcriptional activity of estrogen receptor (ER) α oscillates in phase with the 4-d-long estrous cycle. Here systemic, genome-wide analysis demonstrates that ER tetradian oscillation is necessary to generate pulses of expression in genes for fatty acid and cholesterol synthesis. This ER-dependent metabolic programming changes with pregnancy and after cessation of ovarian function due to age or surgical menopause, suggesting that ER signaling is optimized to coordinate liver functions with the energetic requirements of each reproductive stage. Alterations of amplitude and frequency of the tetradian cycle, as observed after surgical menopause, age, or specific ablation of the hepatic Igf-1 gene, are associated with liver fat deposition. Appropriate hormone replacement therapy reinstating the oscillatory activity of liver ER prevents the effect of surgical menopause on fat deposition in liver.energy metabolism | estrogen action | steroid hormone physiology | selective estrogen receptor modulators E strogen receptor (ER) α (or ESR1 or NR3A) is a transcription factor regulated by estrogens and nonestrogenic substances. ERα is highly expressed in reproductive organs and is indispensable for female reproductive functions (1). ERα is also present in most nonreproductive organs, where its role is currently object of intense investigation because of the large number of dysfunctions associated with the postmenopause and affecting the metabolic, cardiovascular, and immune systems (2-5).Application of the ER responsive element (ERE)-Luc reporter mouse, a transgenic mouse in which the luciferase reporter is driven by a promoter carrying multiple ERE copies (6), identified the liver as the organ in which ERs are most transcriptionally active (7,8). Further studies demonstrated that hepatic ERα transcriptional activity oscillates with the estrous cycle (tetradian oscillation) and is regulated by several compounds, including growth factors and nutritional proteins (9). This latter mechanism is instrumental for the synthesis of the circulating insulin-like growth factor 1 (IGF-1) necessary for the progression of the estrous cycle (9).These studies pointed to the hepatic ERα as a sensor of nutrient availability and a switch able to block the reproductive cycle in the event of malnutrition. On the other hand, a large body of evidence indicates that ERs are important regulators of several aspects of liver energy metabolism. Phenotypic analysis of mutant mice, including ERα (ERKO), ERβ, and aromatase KO mice, demonstrated that ERs play a pivotal role in the regulation of many processes related to the control of energy homeostasis, including energy expenditure, insulin sensitivity, and fat distribution (1, 10-13). In addition, investigation of the genetic programs controlled by hepatic ERs performed by comparing the transcriptomes of vehicle-and 17β-estradiol (E 2 )-treated ovariectomized (ovx) mice (14) established the potential for ER to recognize and regulate the transcription of numerous genes in...

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“…The sonographers were unaware of the participants' clinical and laboratory characteristics. A hyperechogenic pattern was defined as the presence of an ultrasonographic pattern of a bright liver, with evident contrast between hepatic and renal parenchyma (27,28).…”

Section: Measurementsmentioning

confidence: 99%

Association between hepatic steatosis and serum IGF1 and IGFBP-3 levels in a population-based sample

Völzke

Nauck²,

Rettig³

et al. 2009

European Journal of Endocrinology

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Context: It is assumed that hepatic steatosis plays a role in the development and progression of the metabolic syndrome and its cardiovascular sequelae. Low serum IGF1 levels might mediate these associations. Objectives: The aims of this study were i) to investigate the associations of hepatic steatosis with serum IGF1 and IGF binding protein-3 (IGFBP-3) levels using ultrasound and serum alanine aminotransaminase (ALT) data to define hepatic steatosis, and ii) to analyze the specific role of alcohol consumption in this context. Design: We analyzed data from the population-based Study of Health in Pomerania. Methods: We used data from 3863 subjects (1971 women) aged 20-79 years who had no history of viral hepatitis, liver cirrhosis, or malignant diseases. Liver hyperechogenicity was diagnosed using ultrasound. Serum IGF1 and IGFBP-3 levels were determined by automated two-site chemiluminescence immunoassays. Results: Hyperechogenic liver pattern was associated with low serum IGF1 levels and low serum IGF1/IGFBP-3 ratios. The lowest serum IGF1 and IGF1/IGFBP-3 values and highest IGFBP-3 levels were present in subjects who had a hyperechogenic liver pattern and increased serum ALT levels. All of these associations were independent of alcohol consumption. Conclusions: Our data show that hepatic steatosis is associated with low serum IGF1 levels. This association is independent of alcohol consumption.

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Menopausal status and hepatic steatosis in a general female population

Cited by 130 publications

References 11 publications

Resistance training restores the gene expression of molecules related to fat oxidation and lipogenesis in the liver of ovariectomized rats

Resistance training restores the gene expression of molecules related to fat oxidation and lipogenesis in the liver of ovariectomized rats

Tetradian oscillation of estrogen receptor α is necessary to prevent liver lipid deposition

Association between hepatic steatosis and serum IGF1 and IGFBP-3 levels in a population-based sample

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