HGF ameliorates a high-fat diet-induced fatty liver

Kosone, Takashi; Takagi, Hitoshi; Horiguchi, Norio; Ariyama, Yasuyo; Otsuka, Toshiyuki; Sohara, Naondo; Kakizaki, Satoru; Sato, Ken; Mori, Masatomo

doi:10.1152/ajpgi.00021.2007

Cited by 35 publications

(26 citation statements)

References 36 publications

(46 reference statements)

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“…The pathological alterations of livers from different groups were evaluated by measuring hepatic triglyceride contents and circulating liver enzyme levels. Consistent with previous studies (20,33), long-term highfat diet feeding induced liver injury ( Fig. 2A) and fatty liver (Fig.…”

Section: Resultssupporting

confidence: 93%

Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease

Wang

Tong

Pini

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

128

108

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Section: Resultssupporting

confidence: 93%

Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease

Wang

Tong

Pini

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

128

108

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“…Some adaptive responses in the liver can occur to limit triglyceride accretion, such as increased MTP activity and FAO (4,22,42). Whereas MTP activity was unchanged in ob/ϩ mice under HC feeding (see RESULTS), we found increased expression of PPAR␣, L-CPT I, and MCAD (Table 3).…”

Section: Discussionmentioning

confidence: 68%

Partial leptin deficiency favors diet-induced obesity and related metabolic disorders in mice

Begriche¹,

Lettéron²,

Abbey-Toby³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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March 18, 2008; doi:10.1152/ajpendo.00379.2007.-Partial leptin deficiency is not uncommon in the general population. We hypothesized that leptin insufficiency could favor obesity, nonalcoholic steatohepatitis (NASH), and other metabolic abnormalities, particularly under high calorie intake. Thus, mice partially deficient in leptin (ob/ϩ) and their wild-type (ϩ/ϩ) littermates were fed for 4 mo with a standardcalorie (SC) or a high-calorie (HC) diet. Some ob/ϩ mice fed the HC diet were also treated weekly with leptin. Our results showed that, when fed the SC diet, ob/ϩ mice did not present significant metabolic abnormalities except for elevated levels of plasma adiponectin. Under high-fat feeding, increased body fat mass, hepatic steatosis, higher plasma total cholesterol, and glucose intolerance were observed in ϩ/ϩ mice, and these abnormalities were further enhanced in ob/ϩ mice. Furthermore, some metabolic disturbances, such as blunted plasma levels of leptin and adiponectin, reduced UCP1 expression in brown adipose tissue, increased plasma liver enzymes, ␤-hydroxybutyrate and triglycerides, and slight insulin resistance, were observed only in ob/ϩ mice fed the HC diet. Whereas de novo fatty acid synthesis in liver was decreased in ϩ/ϩ mice fed the HC diet, it was disinhibited in ob/ϩ mice along with the restoration of the expression of several lipogenic genes. Enhanced expression of several genes involved in fatty acid oxidation was also observed only in ob/ϩ animals. Leptin supplementation alleviated most of the metabolic abnormalities observed in ob/ϩ fed the HC diet. Hence, leptin insufficiency could increase the risk of obesity, NASH, glucose intolerance, and hyperlipidemia in a context of calorie overconsumption. fatty liver; nonalcoholic steatohepatitis; mitochondria; hyperlipidemia; adiponectin LEPTIN, AN ADIPOKINE EXPRESSED mainly in adipose tissue, plays a central role in the control of food intake and energy expenditure (11, 15) but also in immunity and inflammation (7), tissue repair (28), reproduction, and development (1). Total leptin deficiency in ob/ob mice due to missense leptin (ob) gene mutation leads to morbid obesity, type 2 diabetes, and massive steatosis (11, 33). However, total leptin deficiency is extremely rare in humans (11). In contrast, a larger number of individuals could have low (but not zero) levels of leptin as the consequence of a heterozygous mutation within the ob gene (partial leptin deficiency) (8) or a polymorphism in the 5Ј-untranslated region of the ob gene (16,18,27). Moreover, inherited low levels of leptin could increase the risk of being overweight (or even obese) in humans (8, 16, 32) and mice (5).Food overconsumption combined with decreased physical activity play a major role in the worldwide epidemic of obesity (39). Different genetic traits can modulate positively or negatively the detrimental effects of these environmental factors on body adiposity (9, 39). Because obesity favors insulin resistance, type 2 diabetes, hyperlipemia, steatohepatitis, cardiovascula...

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“…Akt phosphorylation and B-cell lymphoma-extra large expression levels were increased in HGF-Tg mice before and after anti-Fas antibody injection (64). Activation of the microsomal triglyceride transfer protein and apolipoprotein B, accompanied by higher triglyceride levels in the serum were also observed in HGF transgenic mice (65).…”

Section: Hgf Transgenic Micementioning

confidence: 87%

Biological roles of hepatocyte growth factor‑Met signaling from genetically modified animals (Review)

Kato

2017

biom rep

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Abstract. Hepatocyte growth factor (HGF) is produced by stromal and mesenchymal cells, and it stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its cognate receptor, Met. The HGF-Met signaling pathway contributes in a paracrine manner to the development of epithelial organs, exerts regenerative effects on the epithelium, and promotes the regression of fibrosis in numerous organs. Additionally, the HGF-Met signaling pathway is correlated with the biology of cancer types, neurons and immunity. In vivo analyses using genetic modification have markedly increased the profound understanding of the HGF-Met system in basic biology and its clinical applications. HGF and Met knockout (KO) mice are embryonically lethal. Therefore, amino acids in multifunctional docking sites of Met have been exchanged with specific binding motifs for downstream adaptor molecules in order to investigate the signaling potential of the HGF-Met signaling pathway. Conditional Met KO mice were generated using Cre-loxP methodology and characterization of these mice indicated that the HGF-Met signaling pathway is essential in regeneration, protection, and homeostasis in various tissue types and cells. Furthermore, the results of studies using HGF-overexpressing mice have indicated the therapeutic potential of HGF for various types of disease and injury. In the present review, the phenotypes of Met gene-modified mice are summarized. IntroductionHepatocyte growth factor (HGF). HGF was cloned as a growth factor for hepatocytes (1,2), is identical to scatter factor (SF) and was originally discovered as a fibroblast-derived cell motility factor for epithelial cells (3). HGF is located at 7q21, which spans >70 kb in length and consists of 18 exons. It encodes the inactive pre-pro-HGF, a single chain of 728 amino acids (83 kDa), which includes a signal sequence (1-31), a heavy α chain (69 kDa), and a light β chain (34 kDa). The exons encode the α chain, with four kringle structures (highly conserved triple disulfide loop structures), a short spacer region between the α and β chains, and the β chain (Fig. 1A) (4-6).HGF is produced and secreted by adjacent stromal and mesenchymal cells, it contributes to the development of epithelial organs in a paracrine fashion, exerts regenerative effects on epithelia in the liver, kidney, lung, and other tissues, and promotes the regression of fibrosis in numerous organs (7,8). Various growth factors, cytokines, and prostaglandins upregulate HGF gene expression, including basic fibroblast growth factor, oncostatin M, hypoxia-inducible factor 1α and nuclear factor-κB (NF-κB) (9). By contrast, transforming growth factor (TGF)-β1 was demonstrated to markedly downregulate HGF gene expression (10,11).HGF forms a family with HGF-like protein (HLP), a unique protein with a domain structure similar to that of HGF (12). Macrophage stimulating protein (MSP) was discovered as a serum protein that promoted mouse macrophage motility (13) Abbreviatio...

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HGF ameliorates a high-fat diet-induced fatty liver

Cited by 35 publications

References 36 publications

Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease

Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease

Partial leptin deficiency favors diet-induced obesity and related metabolic disorders in mice

Biological roles of hepatocyte growth factor‑Met signaling from genetically modified animals (Review)

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