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Effects of knee loading on obesity-related non-alcoholic fatty liver disease in an ovariectomized mouse model with high-fat diet.

ABSTRACT: AIM:Hormonal and nutritional disorders are the main causes of obesity and non-alcoholic fatty liver disease, especially in the elderly and in postmenopausal women. Although physical activity might alleviate these disorders, the elderly may often have difficulty in carrying out physical exercise. The purpose of this study was to investigate the therapeutic effect of knee loading, a new form of physical stimulation, on the symptoms of obesity and fatty liver. METHODS:Using ovariectomized mice fed a high-fat diet, we evaluated the effect of knee loading that applies gentle cyclic loads to the knee. Female C57BL/6 mice were divided into five groups: control (SCD), high-fat diet (HF), HF with loading (HF?+?L), HF with ovariectomy (HF?+?OVX), and HF?+?OVX with loading (HF?+?OVX?+?L). Except for SCD, mice underwent sham operation or ovariectomy and were maintained on HF diet. After 6 weeks, the mice in the HF?+?L and HF?+?OVX?+?L groups were treated with knee loading for 6 weeks. RESULTS:Compared to the obesity groups (HF and HF?+?OVX), knee loading significantly decreased a gain in body weight, liver weight, and white adipose tissue (all P

SUBMITTER: Tan N

PROVIDER: S-EPMC6143407 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Effects of knee loading on obesity-related non-alcoholic fatty liver disease in an ovariectomized mouse model with high-fat diet.

Tan Nian N Li Xinle X Zhai Lidong L Liu Daquan D Li Jie J Yokota Hiroki H Zhang Ping P

Hepatology research : the official journal of the Japan Society of Hepatology 20180506 10

<h4>Aim</h4>Hormonal and nutritional disorders are the main causes of obesity and non-alcoholic fatty liver disease, especially in the elderly and in postmenopausal women. Although physical activity might alleviate these disorders, the elderly may often have difficulty in carrying out physical exercise. The purpose of this study was to investigate the therapeutic effect of knee loading, a new form of physical stimulation, on the symptoms of obesity and fatty liver.<h4>Methods</h4>Using ovariecto ...[more]

PMID: 29601135

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Project description:BackgroundThe "multiple-hit" hypothesis is currently the most widely accepted theory for non-alcoholic fatty liver disease (NAFLD) pathogenesis. The present study aimed to investigate the effects of the water extract of artichoke (WEA) on NAFLD and its underlying mechanism.MethodsRats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD and then treated with WEA at three doses (0.4, 0.8, and 1.6 g/kg body weight, BW) for 8 weeks. At the end of the intervention, serum biochemical parameters, hepatic antioxidant capacity, hepatic levels of pro-inflammatory cytokines, liver histopathology, hepatic inflammatory gene and lipid metabolism gene expression, and Akt and p-Akt (S473) protein levels were determined.ResultsThe body weight, liver weight, liver triglyceride (TG) and serum levels of TG, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, glucose, and insulin were all significantly reduced in the WEA-treated groups (0.8 and 1.6 g/kg BW) compared with the HFD group (P < 0.01). A significant decrease in hepatic content of malondialdehyde (P < 0.01) and glutathione (P < 0.01), as well as a significant increase in liver superoxide dismutase activity (P < 0.01) were observed in WEA-treated groups (0.8 and 1.6 g/kg BW) compared to the HFD group. In addition, there was a marked decrease in the hepatic levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the WEA-treated groups compared to the HFD group (P < 0.01). In line with these findings, the histopathology of the livers of rats treated with WEA (0.8 and 1.6 g/kg BW) showed a decrease in steatosis, ballooning, and lobular inflammation. Mechanistically, the reduced hepatic TG content might be related to the downregulation of lipogenic genes (SREBP1c, FASN, SCD1) and upregulation of lipolytic gene (PPARα), and the improved insulin signaling might be associated with the observed increase in antioxidant activity and reduction in inflammation in the WEA-treated groups.ConclusionThe hepatoprotective role of WEA in NAFLD may be attributed to its anti-steatotic, antioxidant, anti-inflammatory, and anti-insulin resistance effects.

Project description:Introduction: The pathological progression of non-alcoholic fatty liver disease (NAFLD) is driven by multiple factors, and non-alcoholic steatohepatitis (NASH) represents its progressive form. In our previous studies, we found that bicyclol had beneficial effects on NAFLD/ NASH. Here we aim to investigate the underlying molecular mechanisms of the bicyclol effect on NAFLD/NASH induced by high-fat diet (HFD) feeding. Methods: A mice model of NAFLD/NASH induced by HFD-feeding for 8 weeks was used. As a pretreatment, bicyclol (200 mg/kg) was given to mice by oral gavage twice daily. Hematoxylin and eosin (H&E) stains were processed to evaluate hepatic steatosis, and hepatic fibrous hyperplasia was assessed by Masson staining. Biochemistry analyses were used to measure serum aminotransferase, serum lipids, and lipids in liver tissues. Proteomics and bioinformatics analyses were performed to identify the signaling pathways and target proteins. Data are available via Proteome X change with identifier PXD040233. The real-time RT-PCR and Western blot analyses were performed to verify the proteomics data. Results: Bicyclol had a markedly protective effect against NAFLD/NASH by suppressing the increase of serum aminotransferase, hepatic lipid accumulation and alleviating histopathological changes in liver tissues. Proteomics analyses showed that bicyclol remarkably restored major pathways related to immunological responses and metabolic processes altered by HFD feeding. Consistent with our previous results, bicyclol significantly inhibited inflammation and oxidative stress pathway related indexes (SAA1, GSTM1 and GSTA1). Furthermore, the beneficial effects of bicyclol were closely associated with the signaling pathways of bile acid metabolism (NPC1, SLCOLA4 and UGT1A1), cytochrome P450-mediated metabolism (CYP2C54, CYP3A11 and CYP3A25), biological processes such as metal ion metabolism (Ceruloplasmin and Metallothionein-1), angiogenesis (ALDH1A1) and immunological responses (IFI204 and IFIT3). Discussion: These findings suggested that bicyclol is a potential preventive agent for NAFLD/NASH by targeting multiple mechanisms in future clinical investigations.

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Effects of knee loading on obesity-related non-alcoholic fatty liver disease in an ovariectomized mouse model with high-fat diet.

Publications

Effects of knee loading on obesity-related non-alcoholic fatty liver disease in an ovariectomized mouse model with high-fat diet.

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