Involvement of remnant spleen volume on the progression of steatohepatitis in diet‐induced obese rats after a splenectomy

Inoue, Megumi; Gotoh, Koro; Seike, Masataka; Masaki, Takayuki; Oribe, Junya; Honda, Koichi; Kakuma, Tatsuyuki; Yoshimatsu, Hironobu

doi:10.1111/j.1872-034x.2011.00914.x

Cited by 6 publications

(9 citation statements)

References 25 publications

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“…Reports of the relationship between the spleen and lipid metabolism have emerged: splenectomized rodents showed high cholesterol levels (21), hyperlipidemia (22), and increased intrahepatic fat accumulation (23). Elucidating the kinetics of iron in diabetes and other diseases is expected to lay the foundation for novel irontargeting therapies in the future.…”

Section: Discussionmentioning

confidence: 99%

A Long-Term High-Fat Diet Changes Iron Distribution in the Body, Increasing Iron Accumulation Specifically in the Mouse Spleen

Yamano

Ikeda

Sakama

et al. 2015

J Nutr Sci Vitaminol

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Summary Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifi cally accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD. Key Words iron/spleen/diet, high fat/diabetes mellitus, type 2/DMT1 protein (iron transporter)

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Section: Discussionmentioning

confidence: 99%

A Long-Term High-Fat Diet Changes Iron Distribution in the Body, Increasing Iron Accumulation Specifically in the Mouse Spleen

Yamano

Ikeda

Sakama

et al. 2015

J Nutr Sci Vitaminol

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“…These characteristics are frequently clustered as metabolic syndrome, a major cause of T2D onset in humans [16]. Alterations in immune function have also been observed in MSG-treated obese rats, including splenic dysfunctions [17,18]. Since recent studies suggest that the spleen participates in metabolic and immunological abnormalities present in obesity [17,19,20], the aim of the present study was to evaluate the effect of splenectomy in the hypothalamic obesity induced by neonatal MSG treatment.…”

Section: Introductionmentioning

confidence: 97%

Splenectomy attenuates obesity and decreases insulin hypersecretion in hypothalamic obese rats

et al. 2015

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“…Our data was consistent with previous studies. [ 8 9 26 ] And, we demonstrated that splenectomy worsened metabolism of TC, LDL, and VLDL, in animals fed either a normal or high-fat diet. Some theories have been raised to explain the possible mechanism of splenic regulation of lipid metabolism.…”

Section: Discussionmentioning

confidence: 73%

“…[ 26 ] Interestingly, compared with the total splenectomy, partial splenectomy and hemisplectomy have been shown to result in more diminished lipid dysregulation, suggesting a direct correlation between spleen volume and function. [ 8 9 27 ]…”

Section: Discussionmentioning

confidence: 99%

“…[ 6 7 8 ] Recently, Oishi et al , 2011, and Inoue et al , 2012, found that splenectomy exacerbates triglyceride (TG) deposition in the liver, suggesting a role for the spleen in preventing progression of hepatic steatosis to steatohepatitis. [ 9 10 11 ] The specific mechanism, by which the spleen exerts control over fatty acid metabolism in the liver, however, has not been described.…”

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confidence: 99%

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Nonalcoholic fatty liver disease progression in rats is accelerated by splenic regulation of liver PTEN/AKT

Wang

et al. 2015

Saudi J Gastroenterol

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Background/Aim:The spleen has been reported to participate in the development of nonalcoholic fatty liver disease (NAFLD), but the mechanism has not been fully characterized. This study aims to elucidate how the spleen affects the development of NAFLD in a rat model.Materials and Methods:Following either splenectomy or sham operation, male Sprague–Dawley (SD) rats were fed a high-fat diet to drive the development of NAFLD; animals fed a normal diet were used as controls. Two months after surgery, livers and blood samples were collected. Serum lipids were measured; liver histology, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene expression, and the ratio of pAkt/Akt were determined.Results:Splenectomy increased serum lipids, except triglyceride (TG) and high-density lipoprotein (HDL), in animals fed either a high-fat or normal diet. Furthermore, splenectomy significantly accelerated hepatic steatosis. Western blot analysis and real-time polymerase chain reaction showed splenectomy induced significant downregulation of PTEN expression and a high ratio of pAkt/Akt in the livers.Conclusions:The spleen appears to play a role in the development of NAFLD, via a mechanism involving downregulation of hepatic PTEN expression.

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Involvement of remnant spleen volume on the progression of steatohepatitis in diet‐induced obese rats after a splenectomy

Abstract: These results indicate the importance of preserving splenic tissue. This residual spleen may play an important role in preventing the progression from diet-induced hepatic steatosis to steatohepatitis.

Cited by 6 publications

References 25 publications

A Long-Term High-Fat Diet Changes Iron Distribution in the Body, Increasing Iron Accumulation Specifically in the Mouse Spleen

A Long-Term High-Fat Diet Changes Iron Distribution in the Body, Increasing Iron Accumulation Specifically in the Mouse Spleen

Splenectomy attenuates obesity and decreases insulin hypersecretion in hypothalamic obese rats

Nonalcoholic fatty liver disease progression in rats is accelerated by splenic regulation of liver PTEN/AKT

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