Kupffer cell depletion protects against the steatosis, but not the liver damage, induced by marginal-copper, high-fructose diet in male rats

High-fructose feeding impairs copper status and leads to low copper availability, which is a novel mechanism in obesity-related fatty liver. Copper deficiency-associated hepatic iron overload likely plays an important role in fructose-induced liver injury. Excess iron in the liver is distributed throughout hepatocytes and Kupffer cells (KCs). The aim of this study was to examine the role of KCs in the pathogenesis of nonalcoholic fatty liver disease induced by a marginal-copper high-fructose diet (CuMF). Male weanling Sprague-Dawley rats were fed either a copper-adequate or a marginally copper-deficient diet for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was also given ad libitum. KCs were depleted by intravenous administration of gadolinium chloride (GdCl3) before and/or in the middle of the experimental period. Hepatic triglyceride accumulation was completely eliminated with KC depletion in CuMF consumption rats, which was associated with the normalization of elevated plasma monocyte chemoattractant protein-1 (MCP-1) and increased hepatic sterol regulatory element binding protein-1 expression. However, hepatic copper and iron content were not significantly affected by KC depletion. In addition, KC depletion reduced body weight and epididymal fat weight as well as adipocyte size. Plasma endotoxin and gut permeability were markedly increased in CuMF rats. Moreover, MCP-1 was robustly increased in the culture medium when isolated KCs from CuMF rats were treated with LPS. Our data suggest that KCs play a critical role in the development of hepatic steatosis induced by marginal-copper high-fructose diet.

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Blackcurrant Suppresses Metabolic Syndrome Induced by High-Fructose Diet in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/385976 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Ji Hun Park ◽

Min Chul Kho ◽

Hye Yoom Kim ◽

You Mee Ahn ◽

Yun Jung Lee ◽

...

Keyword(s):

Metabolic Syndrome ◽

Liver Weight ◽

Oral Glucose ◽

Sprague Dawley ◽

High Fructose Diet ◽

Reactive Protein ◽

Triglyceride Accumulation ◽

High Fructose ◽

Amp Activated Protein Kinase

Increased fructose ingestion has been linked to obesity, hyperglycemia, dyslipidemia, and hypertension associated with metabolic syndrome. Blackcurrant (Ribes nigrum; BC) is a horticultural crop in Europe. To induce metabolic syndrome, Sprague-Dawley rats were fed 60% high-fructose diet. Treatment with BC (100 or 300 mg/kg/day for 8 weeks) significantly suppressed increased liver weight, epididymal fat weight, C-reactive protein (CRP), total bilirubin, leptin, and insulin in rats with induced metabolic syndrome. BC markedly prevented increased adipocyte size and hepatic triglyceride accumulation in rats with induced metabolic syndrome. BC suppressed oral glucose tolerance and protein expression of insulin receptor substrate-1 (IRS-1) and phosphorylated AMP-activated protein kinase (p-AMPK) in muscle. BC significantly suppressed plasma total cholesterol, triglyceride, and LDL content. BC suppressed endothelial dysfunction by inducing downregulation of endothelin-1 and adhesion molecules in the aorta. Vascular relaxation of thoracic aortic rings by sodium nitroprusside and acetylcholine was improved by BC. The present study provides evidence of the potential protective effect of BC against metabolic syndrome by demonstrating improvements in dyslipidemia, hypertension, insulin resistance, and obesityin vivo.

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Effect of crude Moringa oleifera Lam. seed extract on the blood markers of metabolic syndrome in high-fructose diet-fed growing Sprague-Dawley rats

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2019-0045 ◽

2019 ◽

Vol 17 (1) ◽

Author(s):

Masiline Mapfumo ◽

Busisani W. Lembede ◽

Ashwell R. Ndhlala ◽

Eliton Chivandi

Keyword(s):

Body Mass ◽

Moringa Oleifera ◽

Seed Extract ◽

Plasma Triglyceride ◽

Female Rats ◽

Male Rats ◽

Sprague Dawley ◽

High Fructose Diet ◽

Sprague Dawley Rats ◽

High Fructose

AbstractBackgroundMoringa oleifera seed has anti-diabetic and anti-obesogenic properties. This study interrogated the effect of crude hydroethanolic M. oleifera seed extract on the blood markers of metabolic syndrome (MetS) in high-fructose diet fed growing Sprague-Dawley rats.MethodsSixty 21-day old female and male Sprague-Dawley rat pups were randomly allocated to and administered one of the following treatment regimens daily for twelve weeks: group I – plain drinking water (PW)+plain gelatine cube (PC), group II – 20% (w/v) fructose solution (FS)+PC, group III – FS+100 mg/kg body mass fenofibrate in gelatine cube (FN), group IV – FS+low dose (50 mg/kg body mass) of M. oleifera in gelatine cube (LMol) and group V – FS+high dose (500 mg/kg body mass) of M. oleifera in gelatine cube (HMol). The rats in each treatment regimen had ad libitum access to a standard rat chow. After the 12-week trial, the rats were subjected to an oral glucose tolerance test and then euthanised 48 h later. Blood was collected. Plasma triglyceride, cholesterol and insulin concentration were determined. HOMA-IR was then computed.ResultsThe high-fructose diet increased (p<0.05) plasma insulin concentration and HOMA-IR in female rats only. It increased plasma triglyceride concentration in both female and male rats and plasma cholesterol concentration in male rats only. The crude hydroethanolic M. oleifera seed extract prevented the high-fructose diet-induced metabolic derangements in male and female rats.ConclusionCrude hydroethanolic M. oleifera seed extract can potentially be used as a prophylactic intervention for diet-induced MetS in children.

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Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00076.2017 ◽

2017 ◽

Vol 313 (2) ◽

pp. E203-E212 ◽

Cited By ~ 23

Author(s):

Natsasi Chukijrungroat ◽

Tanaporn Khamphaya ◽

Jittima Weerachayaphorn ◽

Thaweesak Songserm ◽

Vitoon Saengsirisuwan

Keyword(s):

Sex Differences ◽

Protein Expression ◽

Fatty Liver ◽

Hepatic Steatosis ◽

Male Rats ◽

High Fat ◽

High Fructose Diet ◽

Ovx Rats ◽

High Fructose

The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFD-fed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFD-induced hepatic steatosis.

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Influence of Normo- and Hypogonadal Condition, Hyperuricemia, and High-Fructose Diet on Renal Changes in Male Rats

International Journal of Endocrinology ◽

10.1155/2017/1623597 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Jimena Soutelo ◽

Yanina Alejandra Samaniego ◽

Elsa Zotta ◽

María Cecilia Fornari ◽

Carlos Reyes Toso ◽

...

Keyword(s):

Gender Disparity ◽

Male Rats ◽

Renal Lesion ◽

Treatment Control ◽

High Fructose Diet ◽

High Fructose ◽

Renal Changes ◽

Male Wistar Rats ◽

Progression Of Renal Disease ◽

Oxonic Acid

Background. There is a gender disparity in the incidence, prevalence, and progression of renal disease. The object of this paper is to evaluate the presence and type of renal lesion in normogonadic and hypogonadic male rats in a mild hyperuricemia induced condition and exposed to a high-fructose diet. Methods. 56 adult male Wistar rats were used. Animals were divided into two groups, one normogonadic (NGN) and one hypogonadic (HGN), and each group was divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA). Renal changes were evaluated by measuring glomerulosclerosis, fibrosis, and arteriolar media/lumen (M/L) ratio.Results. The OA and FOA groups presented significantly hypertension (p<0.001). The OA group significantly increased (p<0.05) the percentage of glomerulosclerosis as well as the FOA group (p<0.001). When comparing NGN versus HGN, we observed a trend to a lower glomerulosclerosis in the latter. A higher arteriolar M/L ratio was observed in the OA (p<0.05) and FOA (p<0.001). Conclusion. Hyperuricemia conditions and a high-fructose diet favor blood pressure increase together with changes in the arteriolar media/lumen ratio and renal glomerular damage. These changes were more apparent in normogonadic animals.

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Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms21010360 ◽

2020 ◽

Vol 21 (1) ◽

pp. 360 ◽

Cited By ~ 6

Author(s):

Charng-Cherng Chyau ◽

Hsueh-Fang Wang ◽

Wen-Juan Zhang ◽

Chin-Chu Chen ◽

Shiau-Huei Huang ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Mice Model ◽

High Fat ◽

Alcoholic Fatty Liver ◽

High Fructose Diet ◽

High Fructose ◽

Ant Control ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

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Consumption of post-fermented Jing-Wei Fuzhuan brick tea alleviates liver dysfunction and intestinal microbiota dysbiosis in high fructose diet-fed mice

RSC Advances ◽

10.1039/c9ra02473e ◽

2019 ◽

Vol 9 (30) ◽

pp. 17501-17513

Author(s):

Xiangnan Zhang ◽

Qiu Wu ◽

Yan Zhao ◽

Alim Aimy ◽

Xingbin Yang

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Intestinal Microbiota ◽

Liver Dysfunction ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

High Fructose Diet ◽

High Fructose ◽

Alcoholic Fatty Liver Disease

Fuzhuan brick tea can improve non-alcoholic fatty liver disease (NAFLD) and intestinal microbiota imbalance induced by a high fructose diet (HFD) intake in mice.

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β-Sitosterol mitigates the development of high-fructose diet-induced nonalcoholic fatty liver disease in growing male Sprague–Dawley rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0295 ◽

2020 ◽

Vol 98 (1) ◽

pp. 44-50 ◽

Cited By ~ 1

Author(s):

Nontobeko M. Gumede ◽

Busisani W. Lembede ◽

Pilani Nkomozepi ◽

Richard L. Brooksbank ◽

Kennedy H. Erlwanger ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Liver Lipid ◽

Male Rat ◽

Nonalcoholic Fatty Liver ◽

High Fructose Diet ◽

Group I ◽

High Fructose

Fructose contributes to the development of nonalcoholic fatty liver disease (NAFLD). β-Sitosterol (Bst), a naturally occurring phytosterol, has antihyperlipidaemic and hepatoprotective properties. This study interrogated the potential protective effect of β-sitosterol against NAFLD in growing rats fed a high-fructose diet, modelling children fed obesogenic diets. Forty-four 21 day old male rat pups were randomly allocated to and administered the following treatments for 12 weeks: group I, standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II, SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III, SRC + FS + 100 mg/kg fenofibrate in a gelatine cube; group IV, SRC + FS + 20 mg/kg β-sitosterol gelatine cube (Bst); group V, SRC + PW + Bst. Terminally, the livers were dissected out, weighed, total liver lipid content determined, and histological analyses done. Harvested plasma was used to determine the surrogate biomarkers of liver function. The high-fructose diet caused increased (p < 0.05) hepatic lipid (total) accretion (>10% liver mass), micro- and macrovesicular hepatic steatosis, and hepatic inflammation. β-Sitosterol and fenofibrate prevented the high-fructose diet-induced macrovesicular steatosis and prevented the progression of NAFLD to steatohepatitis. β-Sitosterol can prospectively be used to mitigate diet-induced NAFLD.

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