Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia

Malínská, Hana; Hüttl, Martina; Miklánková, Denisa; Trnovská, Jaroslava; Zapletalová, Iveta; Poruba, Martin; Marková, Irena

doi:10.3390/ijms22094527

Cited by 12 publications

(9 citation statements)

References 51 publications

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“…In addition, some inflammatory pathways, in particular those related to NFκB, are activated by methylglyoxal ( Neves, et al, 2019 ). According to our previous results ( Malinska, et al, 2021 ), hepatic methylglyoxal concentrations well correlated with hepatic triglycerides concentrations. Thus, mitigation of dicarbonyl stress through decreased methylglyoxal and increased Glo1 expression, can protect against NAFLD development and/or progression.…”

Section: Discussionsupporting

confidence: 76%

Hypolipidemic and insulin sensitizing effects of salsalate beyond suppressing inflammation in a prediabetic rat model

et al. 2023

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Background and aims: Low-grade chronic inflammation plays an important role in the pathogenesis of metabolic syndrome, type 2 diabetes and their complications. In this study, we investigated the effects of salsalate, a non-steroidal anti-inflammatory drug, on metabolic disturbances in an animal model of prediabetes—a strain of non-obese hereditary hypertriglyceridemic (HHTg) rats.Materials and Methods: Adult male HHTg and Wistar control rats were fed a standard diet without or with salsalate delivering a daily dose of 200 mg/kg of body weight for 6 weeks. Tissue sensitivity to insulin action was measured ex vivo according to basal and insulin-stimulated 14C-U-glucose incorporation into muscle glycogen or adipose tissue lipids. The concentration of methylglyoxal and glutathione was determined using the HPLC-method. Gene expression was measured by quantitative RT-PCR.Results: Salsalate treatment of HHTg rats when compared to their untreated controls was associated with significant amelioration of inflammation, dyslipidemia and insulin resistance. Specificaly, salsalate treatment was associated with reduced inflammation, oxidative and dicarbonyl stress when inflammatory markers, lipoperoxidation products and methylglyoxal levels were significantly decreased in serum and tissues. In addition, salsalate ameliorated glycaemia and reduced serum lipid concentrations. Insulin sensitivity in visceral adipose tissue and skeletal muscle was significantly increased after salsalate administration. Further, salsalate markedly reduced hepatic lipid accumulation (triglycerides −29% and cholesterol −14%). Hypolipidemic effects of salsalate were associated with differential expression of genes coding for enzymes and transcription factors involved in lipid synthesis (Fas, Hmgcr), oxidation (Pparα) and transport (Ldlr, Abc transporters), as well as changes in gene expression of cytochrome P450 proteins, in particular decreased Cyp7a and increased Cyp4a isoforms.Conclusion: These results demonstrate important anti-inflammatory and anti-oxidative effects of salsalate that were associated with reduced dyslipidemia and insulin resistance in HHTg rats. Hypolipidemic effects of salsalate were associated with differential expression of genes regulating lipid metabolism in the liver. These results suggest potential beneficial use of salsalate in prediabetic patients with NAFLD symptoms.

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Section: Discussionsupporting

confidence: 76%

Hypolipidemic and insulin sensitizing effects of salsalate beyond suppressing inflammation in a prediabetic rat model

et al. 2023

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“…The pathological accumulation of extracellular matrix proteins has metabolic consequences including insulin resistance and adipose tissue inflammation [61,62]. Furthermore, a study conducted by Malinská et al found that the interscapular BAT in the Ovx rats exhibited decreased fatty acid oxidation, lipogenesis, and lipolysis, which might lead to visceral adiposity as well as triglyceride accumulation [63]. Our results are supported by previous literature in which BAT metabolic pathways were impaired in response to ovariectomy and might have contributed to postmenopausal obesity in the long run [63,64].…”

Section: Discussionmentioning

confidence: 99%

Ovariectomy Interferes with Proteomes of Brown Adipose Tissue in Rats

Chou¹,

Lu²,

Liao³

et al. 2022

Int. J. Med. Sci.

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Postmenopausal women exhibit a higher prevalence of obesity due to decreased energy expenditure and increased food intake compared to their premenopausal counterparts. Brown adipose tissue (BAT) plays a key role in energy homeostasis, thus providing us with appealing therapeutic targets in obesity. However, how BAT proteomes are altered in response to low levels of estrogen remains unclear. To better understand the underlying mechanisms between the postmenopausal state and BAT proteomic changes, our study aimed to investigate the effect of ovariectomy on the BAT proteome. In this study, eight-week-old female Sprague Dawley rats were randomly allocated into bilateral ovariectomy (Ovx) and sham operation (Sham) groups. Mass spectrometry was used for proteomics assay and Ingenuity Pathway Analysis was applied to examine the differentially regulated proteins. Of the 1,412 identified proteins, 18 proteins were significantly upregulated, whereas 36 proteins were significantly downregulated in the Ovx group as compared to the Sham group. Our findings demonstrate that the proteins involved in BAT morphology, the browning of white adipose tissue, and metabolic substrates for thermogenesis were regulated by ovariectomy. The dysregulation of proteins by ovariectomy might be related to the disruption of BAT function in the postmenopausal status. Understanding how BAT proteomes are altered in response to ovariectomy may illuminate novel therapeutic strategies for the management of postmenopausal weight gain in the future.

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“…Notably, these rather robust changes in the mass and content of organs and tissues were not accompanied by changes in circulating FFA, and cholesterol, non-fasting glycemia, circulating insulin and glucagon. The explanation could be from previous experimental study in Wistar rats [ 38 ] indicating that organ changes after ovariectomy could precede changes in circulating factors, in this case not only changes of circulating lipids but also of parameters associated with glucose homeostasis. Regarding changes in circulating serum lipids, triglycerides decreased after ovariectomy and increased when estradiol was substituted after ovariectomy.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular, Metabolic and Inflammatory Changes after Ovariectomy and Estradiol Substitution in Hereditary Hypertriglyceridemic Rats

Piťha

Hüttl

Malínská

et al. 2022

IJMS

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Background: If menopause is really independent risk factor for cardiovascular disease is still under debate. We studied if ovariectomy in the model of insulin resistance causes cardiovascular changes, to what extent are these changes reversible by estradiol substitution and if they are accompanied by changes in other organs and tissues. Methods: Hereditary hypertriglyceridemic female rats were divided into three groups: ovariectomized at 8th week (n = 6), ovariectomized with 17-β estradiol substitution (n = 6), and the sham group (n = 5). The strain of abdominal aorta measured by ultrasound, expression of vascular genes, weight and content of myocardium and also non-cardiac parameters were analyzed. Results: After ovariectomy, the strain of abdominal aorta, expression of nitric oxide synthase in abdominal aorta, relative weight of myocardium and of the left ventricle and circulating interleukin-6 decreased; these changes were reversed by estradiol substitution. Interestingly, the content of triglycerides in myocardium did not change after ovariectomy, but significantly increased after estradiol substitution while adiposity index did not change after ovariectomy, but significantly decreased after estradiol substitution. Conclusion: Vascular and cardiac parameters under study differed in their response to ovariectomy and estradiol substitution. This indicates different effects of ovariectomy and estradiol on different cardiovascular but also extracardiac structures.

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Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia

Cited by 12 publications

References 51 publications

Hypolipidemic and insulin sensitizing effects of salsalate beyond suppressing inflammation in a prediabetic rat model

Hypolipidemic and insulin sensitizing effects of salsalate beyond suppressing inflammation in a prediabetic rat model

Ovariectomy Interferes with Proteomes of Brown Adipose Tissue in Rats

Cardiovascular, Metabolic and Inflammatory Changes after Ovariectomy and Estradiol Substitution in Hereditary Hypertriglyceridemic Rats

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