Tissue-specific effects of protein malnutrition on insulin signaling pathway and lipid accumulation in growing rats

Toyoshima, Yuka; Tokita, Reiko; Taguchi, Yusuke; Akiyama-Akanishi, Narumi; Takenaka, Asako; Kato, Harubumi; Chida, Kazuhiro; Hakuno, Fumihiko; Minami, Shiro; Takahashi, Shin‐Ichiro

doi:10.1507/endocrj.ej13-0514

Cited by 27 publications

(38 citation statements)

References 39 publications

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“…IRS-1 and IRS-2 also regulated the adipocyte differentiation (Yamauchi et al 1996, Miki et al 2001. Protein malnutrition enhanced hepatic insulin sensitivity accompanying with increase in IRS-2 protein level (Toyoshima et al 2014). It is also noteworthy that loss of Irs gene in both rodent and fly models result in extended lifespan (Clancy et al 2001, Tatar et al 2001, Tu et al 2002, Kurosu et al 2005.…”

Section: Irssmentioning

confidence: 99%

“…Recently, we have reported that protein malnutrition during the growth phase inhibited animal growth accompanied by reduced circulating IGF1 following reduced hepatic IGF1 synthesis. These animals developed marked accumulation of hepatic triglycerides (Toyoshima et al 2010(Toyoshima et al , 2014. Such a phenotype is typically observed in kwashiorkor, a form of severe protein malnutrition in infants and children.…”

Section: Cross-talk Of Igf Signals With Amino Acid Signalsmentioning

confidence: 99%

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40 YEARS OF IGF1: IGF1 receptor signaling pathways

Hakuno

Takahashi

2018

Journal of Molecular Endocrinology

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327

238

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Insulin-like growth factors (IGFs) bind specifically to the IGF1 receptor on the cell surface of targeted tissues. Ligand binding to the α subunit of the receptor leads to a conformational change in the β subunit, resulting in the activation of receptor tyrosine kinase activity. Activated receptor phosphorylates several substrates, including insulin receptor substrates (IRSs) and Src homology collagen (SHC). Phosphotyrosine residues in these substrates are recognized by certain Src homology 2 (SH2) domain-containing signaling molecules. These include, for example, an 85 kDa regulatory subunit (p85) of phosphatidylinositol 3-kinase (PI 3-kinase), growth factor receptor-bound 2 (GRB2) and SH2-containing protein tyrosine phosphatase 2 (SHP2/Syp). These bindings lead to the activation of downstream signaling pathways, PI 3-kinase pathway and Ras-mitogen-activated protein kinase (MAP kinase) pathway. Activation of these signaling pathways is known to be required for the induction of various bioactivities of IGFs, including cell proliferation, cell differentiation and cell survival. In this review, the well-established IGF1 receptor signaling pathways required for the induction of various bioactivities of IGFs are introduced. In addition, we will discuss how IGF signals are modulated by the other extracellular stimuli or by themselves based on our studies.

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Section: Irssmentioning

confidence: 99%

Section: Cross-talk Of Igf Signals With Amino Acid Signalsmentioning

confidence: 99%

40 YEARS OF IGF1: IGF1 receptor signaling pathways

Hakuno

Takahashi

2018

Journal of Molecular Endocrinology

Self Cite

327

238

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“…We have already reported that protein malnutrition enhances insulin signaling in rat liver followed by accumulation of hepatic lipid [6,7]. In addition, Aoyama et al have reported that triacylglycerol was accumulated in rat liver fed with low-arginine diet [5].…”

Section: Experimental Datamentioning

confidence: 92%

“…In the field of nutrition, we and other groups previously reported that dietary protein-malnutrition or protein-restriction caused growth retardation accompanied by hepatic triglyceride (TG) accumulation which was considered to be a kind of NAFLD [4][5][6][7]. It is well established that growth retardation is caused at least in part by the reduction of plasma insulin-like growth factor-I (IGF-I) level and actually it was reduced in animals fed a diet with protein-malnutrition or -restriction [4,8].…”

Section: Introductionmentioning

confidence: 99%

Study of Effects of Blood Amino Acid and Hormone Level for Controlling Triglyceride Accumulation in the Liver of Rats Using Self-Organizing Map

Masuda¹,

Nakabayashi²,

Shioya³

et al. 2016

IJIIS

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Abstract:Effects of blood amino acid and hormone level for triglyceride accumulation in the liver are revealed in some previous studies by experimental method. Since there are large individual differences in these effects, it needs a lot of rats for such experiments. Simulation can help, sometimes substitute experiment in various fields especially in engineering field. Recently, combining a supercomputer and Artificial Intelligence technique, simulation is expanding its scope. In this study, one of such a simulation technique, Self-Organizing Map (SOM), proposed by Kohonen and it is a kind of the Neural Networks and using for the competitive learning, is applied for classifying effects of blood amino acid and hormone level for controlling triglyceride accumulation in the liver of rats.

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“…Some amino acids, such as arginine and leucine, are also known to stimulate insulin secretion [12,14]. Moreover, our group previously demonstrated that dietary protein malnutrition decreased plasma insulin and insulin-like growth factor 1 concentrations [9,15], and upregulated the protein expression of insulin receptor substrate 2 (IRS2), one of the key mediators of insulin signaling, in the livers of growing rats, resulting in increased insulin sensitivity [16]. These results implied that enhanced insulin sensitivity caused by dietary protein de ciency may mediate fatty liver development.…”

Section: Introductionmentioning

confidence: 95%

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

Otani

Nishi

Koyama

et al. 2020

Preprint

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Background: Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models.Methods: We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks.Results: Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-total-amino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis.Conclusions: Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.

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Tissue-specific effects of protein malnutrition on insulin signaling pathway and lipid accumulation in growing rats

Cited by 27 publications

References 39 publications

40 YEARS OF IGF1: IGF1 receptor signaling pathways

40 YEARS OF IGF1: IGF1 receptor signaling pathways

Study of Effects of Blood Amino Acid and Hormone Level for Controlling Triglyceride Accumulation in the Liver of Rats Using Self-Organizing Map

Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats

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