Role of the spleen in the development of steatohepatitis in high-fat-diet-induced obese rats

2012 ◽  
Vol 237 (4) ◽  
pp. 461-470 ◽  
Author(s):  
Megumi Inoue ◽  
Koro Gotoh ◽  
Masataka Seike ◽  
Takayuki Masaki ◽  
Koichi Honda ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Liver Tissue ◽  
Sham Operation ◽  
Low Grade ◽  
Sprague Dawley ◽  
High Fat ◽  
Obese Rats ◽  
Inflammatory State

Obesity is considered a systemic low-grade inflammatory state. Although the spleen is the main immune organ with a close anatomical relationship with the liver, its role in the progression of fatty liver disease remains uncertain. Therefore, we sought to clarify the functional role of the spleen in the development of steatohepatitis in high-fat (HF)-diet-induced obese rats. Male Sprague-Dawley rats were fed HF food and divided into two groups, a splenectomy (SPX) group and a sham-operation (Sham) group. The liver and abdominal white adipose tissue (WAT) were removed one and six months after surgery, and we evaluated the effects of SPX on WAT and HF-induced fatty liver. SPX rats exhibited worse dyslipidemia and inflammatory changes in WAT one month after surgery. Hepatic steatosis and inflammation were accelerated by SPX, based on the time after surgery. At one month after surgery, the tissue triglyceride content increased in SPX rats, compared with Sham controls ( P < 0.05). The liver histology also showed a worsening of steatosis in those rats. At six months after SPX, dramatic inflammatory and fibrotic changes were observed in liver tissue sections. Hepatic carnitine palmitoyltransferase-1 was suppressed at one and six months after SPX ( P < 0.05 for each). WAT and liver tissue levels of inflammatory markers such as tumor necrosis factor- α, and the expression of Kupffer cells were all increased at six months in SPX rats, compared with Sham controls ( P < 0.05 for each). Our results indicate that the preservation of the spleen contributes to the prevention of the progression of hepatic steatosis to steatohepatitis in obese rats.

scholarly journals Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Maryam Mashmoul ◽  
Azrina Azlan ◽  
Norhafizah Mohtarrudin ◽  
Barakatun Nisak Mohd Yusof ◽  
Huzwah Khaza’ai ◽  
...  
Keyword(s):  
Fatty Liver ◽  
High Fat Diet ◽  
Liver Tissue ◽  
Protective Effects ◽  
High Fat ◽  
Obese Rats ◽  
Saffron Extract

scholarly journals Histidine supplementation alleviates inflammation in the adipose tissue of high-fat diet-induced obese rats via the NF-κB- and PPARγ-involved pathways

2014 ◽  
Vol 112 (4) ◽  
pp. 477-485 ◽  
Author(s):  
Xiaowei Sun ◽  
Rennan Feng ◽  
Yanchuan Li ◽  
Song Lin ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Low Grade ◽  
Obese Women ◽  
Sprague Dawley ◽  
High Fat ◽  
Tnf Α ◽  
Obese Rats ◽  
And Oxidative Stress

Obesity is considered to be accompanied by a chronic low-grade inflammatory state that contributes to the occurrence of many chronic diseases. Our previous study has demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women. However, the in vivo potential mechanisms are not known. The present study was conducted to investigate the mechanisms underlying the effects of histidine on inflammation in a high-fat diet (HFD)-induced female obese rat model. An obese model was established in female Sprague–Dawley rats by HFD feeding for 8 weeks and followed by histidine supplementation for another 4 weeks. The results revealed that HFD-increased body weight and HFD-lowered serum histidine concentrations were significantly reversed by histidine supplementation (P< 0·05). In addition, the serum concentrations of TNF-α, IL-6, C-reactive protein (CRP) and malondialdehyde were significantly reduced and those of superoxide dismutase (SOD) were significantly increased by histidine supplementation when compared with those in obese rats (P< 0·05). Correspondingly, the mRNA expressions of TNF-α, IL-6 and CRP in the adipose tissue were significantly down-regulated and that of CuZnSOD was significantly up-regulated by histidine supplementation (P< 0·05). Histidine supplementation significantly reduced the HFD-induced translocation of NF-κB p65 into the nucleus (P= 0·032) by reducing the phosphorylation of the inhibitor of κBα in the adipose tissue. The results also revealed that the expression of adiponectin was markedly increased both in the serum and in the adipose tissue after histidine supplementation, accompanied by the activation of PPARγ (P= 0·021). These findings indicate that histidine is an effective candidate for ameliorating inflammation and oxidative stress in obese individuals via the NF-κB- and PPARγ-involved pathways.

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

2017 ◽  
Vol 313 (2) ◽  
pp. E203-E212 ◽  
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.

scholarly journals Dissociation of hepatic insulin resistance from susceptibility of nonalcoholic fatty liver disease induced by a high-fat and high-carbohydrate diet in mice

2014 ◽  
Vol 306 (6) ◽  
pp. G496-G504 ◽  
Author(s):  
Akihiro Asai ◽  
Pauline M. Chou ◽  
Heng-Fu Bu ◽  
Xiao Wang ◽  
M. Sambasiva Rao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Diet Group ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Akt Phosphorylation ◽  
High Carbohydrate

Liver steatosis in nonalcoholic fatty liver disease is affected by genetics and diet. It is associated with insulin resistance (IR) in hepatic and peripheral tissues. Here, we aimed to characterize the severity of diet-induced steatosis, obesity, and IR in two phylogenetically distant mouse strains, C57BL/6J and DBA/2J. To this end, mice (male, 8 wk old) were fed a high-fat and high-carbohydrate (HFHC) or control diet for 16 wk followed by the application of a combination of classic physiological, biochemical, and pathological studies to determine obesity and hepatic steatosis. Peripheral IR was characterized by measuring blood glucose level, serum insulin level, homeostasis model assessment of IR, glucose intolerance, insulin intolerance, and AKT phosphorylation in adipose tissues, whereas the level of hepatic IR was determined by measuring insulin-triggered hepatic AKT phosphorylation. We discovered that both C57BL/6J and DBA/2J mice developed obesity to a similar degree without the feature of liver inflammation after being fed an HFHC diet for 16 wk. C57BL/6J mice in the HFHC diet group exhibited severe pan-lobular steatosis, a marked increase in hepatic triglyceride levels, and profound peripheral IR. In contrast, DBA/2J mice in the HFHC diet group developed only a mild degree of pericentrilobular hepatic steatosis that was associated with moderate changes in peripheral IR. Interestingly, both C57BL/6J and DBA/2J developed severe hepatic IR after HFHC diet treatment. Collectively, these data suggest that the severity of diet-induced hepatic steatosis is correlated to the level of peripheral IR, not with the severity of obesity and hepatic IR. Peripheral rather than hepatic IR is a dominant factor of pathophysiology in nonalcoholic fatty liver disease.

Hepatoprotective effect of coffee pulp aqueous extract combined with simvastatin against hepatic steatosis in high-fat diet-induced obese rats

2019 ◽  
Vol 54 ◽  
pp. 568-577 ◽  
Author(s):  
Atcharaporn Ontawong ◽  
Oranit Boonphang ◽  
Tipthida Pasachan ◽  
Acharaporn Duangjai ◽  
Anchalee Pongchaidecha ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Aqueous Extract ◽  
High Fat Diet ◽  
Hepatoprotective Effect ◽  
High Fat ◽  
Coffee Pulp ◽  
Obese Rats

scholarly journals Contrasting Effects of Fasting on Liver-Adipose Axis in Alcohol-Associated and Non-alcoholic Fatty Liver

2021 ◽  
Vol 12 ◽  
Author(s):  
Karuna Rasineni ◽  
Clayton W. Jordan ◽  
Paul G. Thomes ◽  
Jacy L. Kubik ◽  
Elizabeth M. Staab ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Male Rats ◽  
Acid Uptake ◽  
High Fat ◽  
Physiological Mechanisms ◽  
Alcoholic Fatty Liver

Background: Fatty liver, a major health problem worldwide, is the earliest pathological change in the progression of alcohol-associated (AFL) and non-alcoholic fatty liver disease (NAFL). Though the causes of AFL and NAFL differ, both share similar histological and some common pathophysiological characteristics. In this study, we sought to examine mechanisms responsible for lipid dynamics in liver and adipose tissue in the setting of AFL and NAFL in response to 48 h of fasting.Methods: Male rats were fed Lieber-DeCarli liquid control or alcohol-containing diet (AFL model), chow or high-fat pellet diet (NAFL model). After 6–8 weeks of feeding, half of the rats from each group were fasted for 48 h while the other half remained on their respective diets. Following sacrifice, blood, adipose, and the liver were collected for analysis.Results: Though rats fed AFL and NAFL diets both showed fatty liver, the physiological mechanisms involved in the development of each was different. Here, we show that increased hepatic de novo fatty acid synthesis, increased uptake of adipose-derived free fatty acids, and impaired triglyceride breakdown contribute to the development of AFL. In the case of NAFL, however, increased dietary fatty acid uptake is the major contributor to hepatic steatosis. Likewise, the response to starvation in the two fatty liver disease models also varied. While there was a decrease in hepatic steatosis after fasting in ethanol-fed rats, the control, chow and high-fat diet-fed rats showed higher levels of hepatic steatosis than pair-fed counterparts. This diverse response was a result of increased adipose lipolysis in all experimental groups except fasted ethanol-fed rats.Conclusion: Even though AFL and NAFL are nearly histologically indistinguishable, the physiological mechanisms that cause hepatic fat accumulation are different as are their responses to starvation.

scholarly journals The NLRP3 Inflammasome as a Critical Actor in the Inflammaging Process

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1552
Author(s):  
Maria Sebastian-Valverde ◽  
Giulio M. Pasinetti
Keyword(s):  
Nlrp3 Inflammasome ◽  
Low Grade ◽  
Cellular Mechanisms ◽  
Pyrin Domain ◽  
Human Lifespan ◽  
Age Related ◽  
Inflammatory State ◽  
Chronic Activation ◽  
Receptor Family

As a consequence of the considerable increase in the human lifespan over the last century, we are experiencing the appearance and impact of new age-related diseases. The causal relationships between aging and an enhanced susceptibility of suffering from a broad spectrum of diseases need to be better understood. However, one specific shared feature seems to be of capital relevance for most of these conditions: the low-grade chronic inflammatory state inherently associated with aging, i.e., inflammaging. Here, we review the molecular and cellular mechanisms that link aging and inflammaging, focusing on the role of the innate immunity and more concretely on the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, as well as how the chronic activation of this inflammasome has a detrimental effect on different age-related disorders.

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