Systematic analysis of the pharmacological function of Schisandra as a potential exercise supplement

[Purpose] Exercise can prevent conditions such as atrophy and degenerative brain diseases. However, owing to individual differences in athletic ability, exercise supplements can be used to improve a person’s exercise capacity. Schisandra chinensis (SC) is a natural product with various physiologically active effects. In this study, we analyzed SC using a pharmacological network and determined whether it could be used as an exercise supplement.[Methods] The active compounds of SC and target genes were identified using the Traditional Chinese Medicine Database and Analysis Platform (TCMSP). The active compound and target genes were selected based on pharmacokinetic (PK) conditions (oral bioavailability (OB) ≥ 30%, Caco-2 permeability (Caco-2) ≥ -0.4, and drug-likeness (DL) ≥ 0.18). Gene ontology (GO) was analyzed using the Cytoscape software.[Results] Eight active compounds were identified according to the PK conditions. Twenty-one target genes were identified after excluding duplicates in the eight active compounds. The top 10 GOs were analyzed using GO-biological process analysis. GO was subsequently divided into three representative categories: postsynaptic neurotransmitter receptor activity (53.85%), an intracellular steroid hormone receptor signaling pathway (36.46%), and endopeptidase activity (10%). SC is related to immune function.[Conclusion] According to the GO analysis, SC plays a role in immunity and inflammation, promotes liver metabolism, improves fatigue, and regulates the function of steroid receptors. Therefore, we suggest SC as an exercise supplement with nutritional and anti-fatigue benefits.     

Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats

High-calorie food leads to nonalcoholic fatty liver disease (NAFLD) through dysregulation of genes involved in lipid metabolism, but the precise mechanism remains unclear. DNA methylation represents one of the mechanisms that contributes to dysregulation of gene expression via interaction with environmental factors. Berberine can alleviate fatty liver in db/db and ob/ob mice. Here, we investigated whether DNA methylation is involved in the pathogenesis of NAFLD induced by a high-fat diet (HFD) and whether berberine improves NAFLD through influencing the methylation status of promoters of key genes. HFD markedly decreased the mRNA levels encoding CPT-1α, MTTP, and LDLR in the liver. In parallel, DNA methylation levels in the MTTP promoter of rats with NAFLD were elevated in the liver. Interestingly, berberine reversed the downregulated expression of these genes and selectively inhibited HFD-induced increase in the methylation of MTTP. Consistently, berberine increased hepatic triglyceride (TG) export and ameliorated HFD-induced fatty liver. Furthermore, a close negative correlation was observed between the MTTP expression and its DNA methylation (at sites −113 and −20). These data indicate that DNA methylation of the MTTP promoter likely contributes to its downregulation during HFD-induced NAFLD and, further, that berberine can partially counteract the HFD-elicited dysregulation of MTTP by reversing the methylation state of its promoter, leading to reduced hepatic fat content.     

The effects of either resveratrol or exercise on macrophage infiltration and switching from M1 to M2 in high fat diet mice

[Purpose]

The aim of this study was to compare the effectiveness of either resveratrol supplementation or exercise training on macrophage infiltration and switching from M1 to M2 kupffer cells in high fat diet mice.

[Methods]

C57BL/6 mice were separated into 5 groups: normal diet (ND; n = 6), high-fat diet (HD; n = 6), high-fat diet with resveratrol (HR; n = 6), high-fat diet with exercise (HE; n = 6) or high-fat diet with resveratrol and exercise (HRE; n = 6). Resveratrol supplementation mice were orally gavaged with resveratrol (25mg/kg of body weight) dissolved in 50% propylene glycol. Exercise mice ran on a treadmill at 12-20 m/min for 30-60 min/day, 5 times/week for 12 weeks.

[Results]

After 12 weeks of intervention, the liver was analyzed. F4/80 expression was evaluated by western blot while CD11c and CD163 mRNA expressions were evaluated by RT-PCR. The weights of the body and liver were significantly increased in the HD and HR group compared to the ND group (p < 0.01). However, the weights were most effectively reduced in the HE and HRE groups compared to the HD group (p < 0.05). The macrophage marker, F4/80 expression was significantly lower in the HE and HRE groups compared to the HD group (p < 0.05). mRNA expression of the M1 macrophage marker, CD11c, in the HD group was significantly increased compared to the ND group (p < 0.01). mRNA expression of the M2 macrophage specific marker, CD163, in the HE and HRE groups were significantly increased compared to the HD group (p < 0.05). The mRNA expressions of TLR4, ICAM-1 and VCAM-1, which induce pro-inflammatory cytokine production, were strongly decreased in the HR, HE, and HRE groups compared to the HD group.

[Conclusion]

These results suggest that moderate exercise training inhibits macrophage infiltration and up regulation of CD163 expression. However, resveratrol supplementation is not enough to ameliorate obesity-induced macrophage infiltration and switching.     

Hepatic Methionine Homeostasis Is Conserved in C57BL/6N Mice on High-Fat Diet Despite Major Changes in Hepatic One-Carbon Metabolism

Obesity is an underlying risk factor in the development of cardiovascular disease, dyslipidemia and non-alcoholic fatty liver disease (NAFLD). Increased hepatic lipid accumulation is a hallmark in the progression of NAFLD and impairments in liver phosphatidylcholine (PC) metabolism may be central to the pathogenesis. Hepatic PC biosynthesis, which is linked to the one-carbon (C1) metabolism by phosphatidylethanolamine N-methyltransferase, is known to be important for hepatic lipid export by VLDL particles. Here, we assessed the influence of a high-fat (HF) diet and NAFLD status in mice on hepatic methyl-group expenditure and C1-metabolism by analyzing changes in gene expression, protein levels, metabolite concentrations, and nuclear epigenetic processes. In livers from HF diet induced obese mice a significant downregulation of cystathionine β-synthase (CBS) and an increased betaine-homocysteine methyltransferase (BHMT) expression were observed. Experiments in vitro, using hepatoma cells stimulated with peroxisome proliferator activated receptor alpha (PPARα) agonist WY14,643, revealed a significantly reduced Cbs mRNA expression. Moreover, metabolite measurements identified decreased hepatic cystathionine and L-α-amino-n-butyrate concentrations as part of the transsulfuration pathway and reduced hepatic betaine concentrations, but no metabolite changes in the methionine cycle in HF diet fed mice compared to controls. Furthermore, we detected diminished hepatic gene expression of de novo DNA methyltransferase 3b but no effects on hepatic global genomic DNA methylation or hepatic DNA methylation in the Cbs promoter region upon HF diet. Our data suggest that HF diet induces a PPARα-mediated downregulation of key enzymes in the hepatic transsulfuration pathway and upregulates BHMT expression in mice to accommodate to enhanced dietary fat processing while preserving the essential amino acid methionine.     

Effect of aerobic exercise training on non-alcoholic fatty liver disease induced by a high fat diet in C57BL/6 mice

[Purpose]

The aim of this study was to investigate the effects of aerobic exercise training on a high fat diet (HFD)-induced fatty liver and its metabolic complications in C57BL/6 mice.

[Methods]

Mice at 5-month old (n = 30) were randomly assigned to standard chow (SC + CON, n = 10) and high-fat diet (HFD, n = 20), and they were subjected to SC and HFD, respectively, for 23-week. After 15-week of HFD, mice in the HFD group were further assigned to HFD (HFD + CON, n = 10) or exercise training (HFD + EX, n = 10) groups. The HFD + EX mice were subjected to aerobic treadmill running during the last 8-week of the 23-week HFD course. Outcomes included hepatic steatosis, insulin resistance, and expression of genes involved in mitochondrial function and/or fatty oxidation as well as de novo lipogenesis and/or triacylglycerol (TAG) synthesis.

[Results]

Treadmill running ameliorated impaired glucose tolerance and insulin resistance secondary to the HFD. The beneficial effects of treadmill running were associated with enhanced molecular markers of mitochondrial function and/or fatty acids oxidation (i.e., PPARα and CPT1a mRNAs, pAMPK/AMPK, pACC, and SIRT1 protein) as well as suppressed expression of de novo lipogenesis and/or TAG synthesis (i.e., SREBP1c, lipin1 and FAS mRNAs) in the liver.

[Conclusion]

The current findings suggest that aerobic exercise training is an effective and non-pharmacological means to combat fatty liver and its metabolic complications in HFD-induced obese mice.     

葛仙米多糖对高脂小鼠血脂和肠道微生物的影响

[目的]研究葛仙米多糖对高脂饲料喂养小鼠血脂和肠道微生物的影响.[方法]将健康的8周龄雄性小鼠分成5组,每组10只:正常组C57/6CNC小鼠(N:灌胃生理盐水,喂饲标准饲料),对照组ApoE-/-小鼠(C:灌胃生理盐水,喂饲标准饲料),模型组ApoE-/-小鼠(M:灌胃生理盐水,喂饲高脂高胆固醇饲料),葛仙米多糖低剂...     

Protective effect of Hedansanqi Tiaozhi Tang against non-alcoholic fatty liver disease in vitro and in vivo through activating Nrf2/HO-1 antioxidant signaling pathway

BackgroundHedansanqi Tiaozhi Tang extract (HTT) consists of Notoginseng, Danshen, Hawthorn and Lotus leaf from traditional Chinese medicine, which has significant therapeutic effects on hyperlipidemia in patients with non-alcoholic fatty liver disease (NAFLD).PurposeThis study sought to evaluate the pharmacological effects and molecular mechanism of HTT for the treatment of hyperlipidemia in adipocytes and animal model with NAFLD.MethodsQuantitative phytochemical analysis of HTT was performed by HPLC. Antioxidant activity and the adipogenesis in 3T3-L1 cells were assessed. In the rat model induced by high-fat diet, lipid-related and antioxidant markers in serum and liver were detected. Moreover, the organ weights, non-alcoholic steatohepatitis (NASH) score and the levels of Nrf2 and HO-1 in liver sections were analyzed by tissue pathological techniques.Results8 constituents were identified in HTT including saponins, flavonoids, alkaloids and others. HTT treatment enhanced antioxidant activities and promoted lipolysis in 3T3-L1 adipocytes. We also found that HTT inhibited weight gain, reduced the lipid profiles and improved the liver function and pathological characteristics induced by high-fat diet. In addition, HTT activated the Nrf2/HO-1 antioxidant pathway in the liver.ConclusionHTT has protective effect against NAFLD in vitro and in vivo by activating the Nrf2/HO-1 antioxidant pathway.     

Phytotherapy using blueberry leaf polyphenols to alleviate non-alcoholic fatty liver disease through improving mitochondrial function and oxidative defense

BackgroundSince non-alcoholic fatty liver disease (NAFLD) pathogenesis is multi-factorial, pharmacotherapy with a specific target commonly exhibits limited efficacy. Phytotherapy, whose therapeutic efficacy is based on the combined action of several active compounds, offers new treatment opportunity for NAFLD. As a representative, many natural polyphenols could be utilized in phytotherapy for NAFLD.PurposeIn present work, we aimed to investigate the therapeutic effects and underlying mechanism of polyphenols in blueberry leaves (PBL) on NAFLD from a mitochondria-centric perspective since mitochondrial dysfunction could play a dominant role in NAFLD.MethodsIdentification and quantification of PBL were performed using liquid chromatography coupled with tandem mass spectrometry. The beneficial effects, especially improving mitochondrial function, and potential mechanism of PBL on NAFLD were studied by in vitro and in vivo study.ResultsPolyphenols were abundant in blueberry leaves making it advantaged in NAFLD phytotherapy. PBL effectively alleviated hepatic steatosis, oxidative stress and inflammation as indicated by both in vitro and in vivo study. Furthermore, PBL mediated improvement of mitochondrial dysfunction and antioxidant capability through activation of AMPK/PGC-1α/SIRT3 signaling axis.ConclusionConsidering that mitochondrial dysfunction takes precedence over hepatic steatosis and induces NAFLD development, we conclude that PBL improve mitochondrial dysfunction and oxidative defense, subsequently alleviate hepatic steatosis, oxidative stress and inflammation, and eventually alleviate NAFLD.     

Serum levels of appetite-regulating hormones and pro-inflammatory cytokines are ameliorated by a CLA diet and endurance exercise in rats fed a high-fat diet

[Purpose]

This study examined whether conjugated linoleic acid (CLA) supplementation and endurance exercise affect appetite-regulating hormones and pro-inflammatory cytokines in rats.

[Methods]

Seven-week-old male Sprague-Dawley rats were divided randomly into the high-fat diet sedentary group (HS, n=8), the 1.0% CLA supplemented high-fat diet sedentary group (CS, n=8), and the 1.0% CLA supplemented high-fat diet exercise group (CE, n=8). Rats in the CE group swam 60 min/day, 5 days/week for 4 weeks.

[Results]

Leptin and insulin levels in the CS and CE groups were significantly lower than those in the HS group (p<0.001), whereas leptin (p<0.01) and insulin (p<0.05) levels decreased significantly in the CE compared to those in the CS group. Interleukin (IL)-1β (p<0.001) and IL-6 (p<0.01) levels in the CS and CE groups decreased significantly compared to those in the HS group. Leptin (IL-1β: r=0.835, p<0.001), IL-6 (r=0.607, p<0.05), insulin (IL-1β: r=0.797, p<0.01), and IL-6 (r=0.827, p<0.01) levels were positively related with pro-inflammatory cytokine levels.

[Conclusion]

Endurance exercise may play an important role during CLA supplementation of rats on a high-fat diet.     

Phosphorylation of eIF2α signaling pathway attenuates obesity-induced non-alcoholic fatty liver disease in an ER stress and autophagy-dependent manner

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder and frequently exacerbates in postmenopausal women. In NAFLD, the endoplasmic reticulum (ER) plays an important role in lipid metabolism, in which salubrinal is a selective inhibitor of eIF2α de-phosphorylation in response to ER stress. To determine the potential mechanism of obesity-induced NAFLD, we employed salubrinal and evaluated the effect of ER stress and autophagy on lipid metabolism. Ninety-five female C57BL/6 mice were randomly divided into five groups: standard chow diet, high-fat (HF) diet, HF with salubrinal, HF with ovariectomy, and HF with ovariectomy and salubrinal. All mice except for SC were given HF diet. After the 8-week obesity induction, salubrinal was subcutaneously injected for the next 8 weeks. The expression of ER stress and autophagy markers was evaluated in vivo and in vitro. Compared to the normal mice, the serum lipid level and adipose tissue were increased in obese mice, while salubrinal attenuated obesity by blocking lipid disorder. Also, the histological severity of hepatic steatosis and fibrosis in the liver and lipidosis was suppressed in response to salubrinal. Furthermore, salubrinal inhibited ER stress by increasing the expression of p-eIF2α and ATF4 with a decrease in the level of CHOP. It promoted autophagy by increasing LC3II/I and inhibiting p62. Correlation analysis indicated that lipogenesis in the development of NAFLD was associated with ER stress. Collectively, we demonstrated that eIF2α played a key role in obesity-induced NAFLD, and salubrinal alleviated hepatic steatosis and lipid metabolism by altering ER stress and autophagy through eIF2α signaling.Subject terms: Obesity, Metabolic syndrome, Outcomes research     

Chitosan reduces inflammation and protects against oxidative stress in a hyperlipidemic rat model: relevance to nonalcoholic fatty liver disease

Background

An altered lipid profile may lead to the development of inflammation and NAFLD (Non-alcoholic fatty liver disease). Although statins have a positive effect on blood lipid levels their long-term use is known to cause adverse effects, in this backdrop there is an interest in natural compounds which may affect lipid metabolism and prevent NAFLD. We have examined the effect of Chitosan on rats subjected to a high-fat diet.

Methods and results

Male Wistar middle aged rats (12–16 months) were treated with high-fat diet orally for two months for creating a NAFLD model. Rats were also supplemented with Chitosan (2% chitosan daily) for 2 months. We assessed the activity of antioxidant enzymes, the histopathological profile of the liver. Inflammatory cytokines and adiponectin levels were also measured in serum. HFD induced significant changes in liver tissue and inflammatory markers (Il-6, TNF- alpha, NF-KB). Chitosan treatment protected rats from HFD induced alterations.

Conclusions

The findings suggest that Chitosan can effectively improve liver lipid metabolism by normalizing cholesterol, triglyceride, lowering NF-KB expression, and protecting the liver from oxidative stress by improving hepatic function. Chitosan also regulates genes related to lipidemic stress i,e leptin and adiponectin.

     

Naturally Occurring Stilbenoid TSG Reverses Non-Alcoholic Fatty Liver Diseases via Gut-Liver Axis

The gut-liver axis is largely involved in the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether 2, 3, 5, 4′-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) could reverse NAFLD induced by a high-fat diet (HFD) and whether it did so via the gut-liver axis. Results showed that TSG could reduce the accumulation of FFA and it did so by reducing the expression of L-FABP and FATP4. TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%. TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group. This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.     

Consumption of a high-fat-high-sucrose diet partly diminishes mechanical and structural adaptations of cardiac muscle following resistance training

[Purpose]The purpose of this study was to investigate the effects of a high-fat high-sucrose (HFHS) diet on previously reported adaptations of cardiac morphological and contractile properties to resistance training.[Methods]Twelve-week-old rats participated in 12-weeks of resistance exercise training and consumed an HFHS diet. Echocardiography and skinned cardiac muscle fiber bundle testing were performed to determine the structural and mechanical adaptations.[Results]Compared to chow-fed sedentary animals, both HFHS- and chow-fed resistance-trained animals had thicker left ventricular walls. Isolated trabecular fiber bundles from chow-fed resistance-trained animals had greater force output, shortening velocities, and calcium sensitivities than those of chow-fed sedentary controls. However, trabeculae from the HFHS resistance-trained animals had greater force output but no change in unloaded shortening velocity or calcium sensitivity than those of the chow-fed sedentary group animals.[Conclusion]Resistance exercise training led to positive structural and mechanical adaptations of the heart, which were partly offset by the HFHS diet.     

Anti-inflammatory and antioxidant activities of Sargassum horneri extract in RAW264.7 macrophages

[Purpose]In this study, we investigated whether a 70% ethanolic (EtOH) extract of Sargassum horneri had antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophage-like RAW 264.7 cells.[Methods]The proximate composition, fatty acids, amino acids, and dietary fiber of S. horneri, various biologically active compounds, and antioxidant activity were analyzed.[Results]The DPPH and ABTS free radical scavenging activities, as well as the reduction power, of the S. horneri extract used here were significantly increased in a concentration-dependent manner. This indicates that S. horneri contains bioactive compounds, such as phenols and flavonoids, that have excellent antioxidant activity. The cellular viability and metabolic activity results confirmed that the extract had no discernible toxicity at concentrations up to 100 μg/mL. The levels of nitrites and cytokines (PGE₂, TNF-α and IL-6), which mediate pro-inflammatory effect, were significantly inhibited by treatment with either 50 or 100 μg/mL S. horneri extract, whereas that of IL-1β was significantly inhibited by treatment with 100 μg/mL of the extract. Similarly, the expression of iNOS and COX-2 proteins also decreased according to 50 or 100 μg/mL extract concentrations. NF-κB binding to DNA was also significantly inhibited by treatment with 100 μg/mL of extract.[Conclusion]These results suggest that 70% EtOH extracts of S. horneri can relieve inflammation caused by disease or high intensity exercise.     

The effect of exercise on expression of myokine and angiogenesis mRNA in skeletal muscle of high fat diet induced obese rat

[Purpose]

The purpose of this study was to investigate the effect of regular treadmill exercise on the mRNA expressions of myokines and angiogenesis factors in the skeletal muscle of obese rats.

[Methods]

Thirty two male Sprague-Dawley rats (4weeks old) were divided into the CO (control) and HF (high fat diet) groups. Obesity was induced in the HF group by consumption of 45% high-fat diet for 15 weeks. These groups were further subdivided into training groups (COT and HFT); the training groups conducted moderate intensity treadmill training for 8 weeks. Soleus muscles were excised and analyzed by real-time quantitative PCR.

[Results]

mRNA expression of myokines, such as PGC-1α, IL-6, and IL-15, in the COT and HFT groups (which conducted regular exercise), were higher as compared with the CO and HF groups (p < 0.05). Also, the levels in the HF group were significantly lower when compared with CO group (p < 0.05). Expression of angiogenesis mRNA, namely mTOR, VEGF, and FLT1, were significantly lower in the HF group, as compared to the CO group (p < 0.05). In addition, COT group had a higher expression of mTORC1, mTORC2, VEGF and FLT mRNA, than the CO group (p < 0.05); the HFT group also had higher expressions of mTOR, VEGF and FLT1 mRNA than the HF group (p < 0.05).

[Conclusion]

These results indicate that mRNA expression of myokines was increased through the activity of muscle contraction, and it also promoted the mRNA expression of angiogenesis due to activation of mTOR. Thus, we conclude that not only under normal health conditions, but in obesity and excess nutritional circumstances also, regular exercise seems to act positively on the glycemic control and insulin sensitivity through the angiogenesis signaling pathway.     

Nicotinamide riboside,an NAD+ precursor,attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis

ObjectiveLiver fibrosis is part of the non-alcoholic fatty liver disease (NAFLD) spectrum, which currently has no approved pharmacological treatment. In this study, we investigated whether supplementation of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor, can reduce the development of liver fibrosis in a diet-induced mouse model of liver fibrosis.MethodsMale C57BL/6 J mice were fed a low-fat control (LF), a high-fat/high-sucrose/high-cholesterol control (HF) or a HF diet supplemented with NR at 400 mg/kg/day (HF-NR) for 20 weeks. Features of liver fibrosis were assessed by histological and biochemical analyses. Whole-body energy metabolism was also assessed using indirect calorimetry. Primary mouse and human hepatic stellate cells were used to determine the anti-fibrogenic effects of NR in vitro.ResultsNR supplementation significantly reduced body weight of mice only 7 weeks after mice were on the supplementation, but did not attenuate serum alanine aminotransferase levels, liver steatosis, or liver inflammation. However, NR markedly reduced collagen accumulation in the liver. RNA-Seq analysis suggested that the expression of genes involved in NAD+ metabolism is altered in activated hepatic stellate cells (HSCs) compared to quiescent HSCs. NR inhibited the activation of HSCs in primary mouse and human HSCs. Indirect calorimetry showed that NR increased energy expenditure, likely by upregulation of β-oxidation in skeletal muscle and brown adipose tissue.ConclusionNR attenuated HSC activation, leading to reduced liver fibrosis in a diet-induced mouse model of liver fibrosis. The data suggest that NR may be developed as a potential preventative for human liver fibrosis.     

Olive oil-derived nitro-fatty acids: protection of mitochondrial function in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive liver fat deposition in the absence of significant alcohol intake. Since extra virgin olive oil (EVOO) reduces fat accumulation, we analyzed the involvement of nitro-fatty acids (NO₂-FA) on the beneficial effects of EVOO consumption on NAFLD. Nitro-fatty acids formation was observed during digestion in mice supplemented with EVOO and nitrite. Mice fed with a high-fat diet (HF) presented lower plasma NO₂-FA levels than normal chow, and circulating concentrations recovered when the HF diet was supplemented with 10% EVOO plus nitrite. Under NO₂-FA formation conditions, liver hemoxygenase-1 expression significantly increased while decreased body weight and fat liver accumulation. Mitochondrial dysfunction plays a central role in the pathogenesis of NAFLD while NO₂-FA has been shown to protect from mitochondrial oxidative damage. Accordingly, an improvement of respiratory indexes was observed when mice were supplemented with both EVOO plus nitrite. Liver mitochondrial complexes II and V activities were greater in mice with EVOO supplementation and further improved in the presence of nitrite. Overall, our results strongly suggest a positive correlation between NO₂-OA formation from EVOO and the observed improvement of mitochondrial function in NAFLD. The formation of NO₂-FA can account for the health benefits associated with EVOO consumption.     

Voluntary exercise training improves body weight of leptin-deficient ob/ob mice by altering hepatic stearoyl-CoA desaturase 1 and deleted in breast cancer 1 protein levels

[Purpose]Deleted in breast cancer 1 (DBC1) ablation causes obesity, and stearoyl-CoA desaturase 1 (SCD1) induces the biosynthesis of monounsaturated fatty acids. This study examined whether voluntary wheel running (VWR) alters SCD-1 and DBC1 protein levels in the liver of leptin-deficient ob/ob mice.[Methods]Twenty-five Ob/Ob mice were divided into two groups (ob/ob-Sed and ob/ob-Ex). The expression of DBC1 and SCD1 in the mouse liver was determined using western blotting.[Results]After 10 weeks, VWR significantly reduced body weight without affecting the fatty acid synthase and CD36 protein levels. The average daily running distance was 4.0±1.0 km/day. This improvement was associated with changes in the hepatic SCD1 and DBC1 levels. Hepatic SCD-1 protein levels increased significantly, and DBC1 protein levels decreased in ob/ob-Sed animals. On the other hand, VWR inhibited the obesity-induced increase in SCD1 expression and impaired the obesity-induced decrease in DBC1 expression in the liver of leptin-deficient ob/ob mice.[Conclusion]This is the first study showing that VWR has strong effects on hepatic SCD1 and DBC1 in ob/ob mice, and provides key insights into the effects of exercise on obesity.     

Study on the correlation between urinary retinol-binding protein and nonalcoholic fatty liver disease

BackgroundNonalcoholic fatty liver disease (NAFLD) affects human health worldwide. Our objective was to explore the correlation between urinary retinol-binding protein (URBP) and NAFLD.MethodsThis cross-sectional study included 445 NAFLD patients and 911 healthy controls. The URBP level and other parameters were measured.ResultsThe URBP level (expressed by the RBP/creatinine ratio) was higher in the NAFLD patients compared with the non-NAFLD patients. The urinary RBP/creatinine ratio was an independent risk factor for NAFLD after univariate and multivariate regression analysis, with the or values of 2.271 (1.795-2.872, P < 0.001) and 2.338 (1.775-3.080, P < 0.001), respectively. The prevalence of the urinary RBP/creatinine ratio (groups 1, 2, 3, 4) was 20.0%, 17.3%, 27.3%, and 35.4%, respectively (P < 0.001), and the prevalence of NAFLD in the high urinary RBP/creatinine ratio group was significantly higher than that in the low urinary RBP/creatinine ratio group.ConclusionsOur results revealed that the urinary RBP/creatinine ratio was an independent risk factor for NAFLD.     

Regulatory effect of diosgenin on lipogenic genes expression in high-fat diet-induced obesity in mice

Obesity is one of the most serious health problems in the world, increasing the risk of other chronic diseases. Alterations in fatty acid synthesis related genes are crucially involved in obesity progression. Diosgenin (DG) was one of the phytosterols compounds with vital activity against lipid disorders. Therefore, this study was intended to evaluate the protective effect of DG on lipogenesis in the high-fat diet (HFD)-induced obesity in mice, via investigating the expression of two of the fatty acid synthesis–involved genes; sterol regulatory element-binding protein (SREBP-1c) and fatty acid synthase (FASN) genes. Thirty adult male mice were divided into 3 groups. Control group, fed with normal diet; HFD group, mice fed with a high-fat diet and HFD + DG group, mice fed with a high-fat diet and supplemented in parallel with DG for 6 consecutive weeks. The effect of DG on Body weights, liver enzymes, lipid profile, were evaluated. Histopathological fatty changes as well as SREBP-1c and FASN gene expression were also investigated. DG significantly alleviated body weight gain, adjusted liver enzymes, and improved lipid profile. Additionally, DG ameliorated the histopathological changes by reducing the lipid vacuoles and hence the hepatosteatosis. Accordingly, DG significantly downregulated the two-fold increase in the SREBP-1c and FASN gene expression observed in the HFD group. In conclusion, DG possesses a beneficial impact against diet-induced obesity in mice, which makes it a good candidate for NAFLD and obesity prevention.