Hepatic senescence marker protein-30 is involved in the progression of nonalcoholic fatty liver disease

Park, Hyohun; Ishigami, Akihito; Shima, Toshihide; Mizuno, Masayuki; Maruyama, Naoki; Yamaguchi, Kanji; Mitsuyoshi, Hironori; Minami, Masahito; Yasui, Kohichiroh; Itoh, Yoshito; Yoshikawa, Toshikazu; Fukui, Michiaki; Hasegawa, Goji; Nakamura, Naoto; Ohta, Mitsuhiro; Obayashi, Hiroshi; Okanoue, Takeshi

doi:10.1007/s00535-009-0154-3

Cited by 41 publications

(32 citation statements)

References 33 publications

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“…Though there is no disagreement regarding the usefulness of exercise therapy as treatment, additional scientif ic validation is needed to determine the optimal exercise parameters for preventing fatty liver. Reports of telomere shortening 77) and decreased expression of senescence marker protein-30 in cases progressing to NASH 78) are highly interesting in the context of associations between aging and pathologic progression of NASH; these observations portend an understanding of the pathology informed by aging, and the development of relevant modes of treatment.…”

Section: Resultsmentioning

confidence: 99%

Science of Nonalcoholic Fatty Liver Disease in Anti-Aging Medicine 2011

et al. 2012

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Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease caused primarily by obesity, and its incidence among Japanese adults is rapidly rising at 10-40%. Most NAFLD presents as simple steatosis, but some are nonalcoholic steatohepatitis (NASH) progressing to hepatic cirrhosis or hepatocellular carcinoma. NAFLD is diagnosed by the following three features; (1) alcohol non-consumers ("non-drinkers"), (2) steatosis, and (3) exclusion of liver disease caused by other factors, with non-drinkers including light consumers of alcohol in amounts not engendering alcoholic liver disease. Dietary treatment is the basis of therapy, but evidence concerning exercise therapy has accumulated recently, and its mechanisms have been explained. Dehydroepiandrosterone (DHEA) is an androgenic intermediate metabolite produced by the adrenals and known as an Anti-Aging hormone with an improving effect on insulin resistance, an antioxidant effect, and an antifibrotic effect. Serum dehydroepiandrosterone sulfate (DHEA-s) has been shown to present low levels in advanced stages of NAFLD and diminished DHEA may contribute to progression of NAFLD. Growth hormone (GH) plays a crucial role not only in childhood growth but also in adult metabolic regulation, and adult GH deficiency (GHD) leads to increased visceral fat, dyslipidemia, and decreased QOL. Complicating NAFLD/NASH is a frequent occurrence in adult GHD and is improved by GH replacement therapy. On this basis, aging is an important risk factor for progression of NASH, which suggests a need for discussion of NASH and NAFLD from the perspective of Anti-Aging Medicine.

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Section: Resultsmentioning

confidence: 99%

Science of Nonalcoholic Fatty Liver Disease in Anti-Aging Medicine 2011

et al. 2012

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“…The designation, nonalcoholic fatty liver disease (NAFLD) applies to a range of fatty liver diseases including simple hepatic steatosis (the abnormal accumulation of lipids in cells), steatohepatitis, and even cirrhosis that are caused by neither alcoholic abuse nor hepatitis infection (27, 70, 71). It was estimated that in 2006, NAFLD affected 16–23% of the US population (70).…”

Section: Nonalcoholic Fatty Liver Disease and Liver Fibrosis In Smp30mentioning

confidence: 99%

“…It was estimated that in 2006, NAFLD affected 16–23% of the US population (70). Hyperlipidemia, insulin resistance, oxidative stress, and especially obesity are believed to contribute to NAFLD development (27, 70, 71). Over 90 percent of people with a body mass index of 39 kg/m 2 or greater have NAFLD (70).…”

Section: Nonalcoholic Fatty Liver Disease and Liver Fibrosis In Smp30mentioning

confidence: 99%

Senescence marker protein 30: functional and structural insights to its unknown physiological function

Scott

Bahnson

2011

BioMolecular Concepts

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Senescence marker protein 30 (SMP30) is a multifunctional protein involved in cellular Ca2+ homeostasis and the biosynthesis of ascorbate in non-primate mammals. The primary structure of the protein is highly conserved among vertebrates, suggesting the existence of a significant physiological function common to all mammals, including primates. Enzymatic activities of SMP30 include aldonolactone and organophosphate hydrolysis. Protective effects against apoptosis and oxidative stress have been reported. X-ray crystallography revealed that SMP30 is a six-bladed β-propeller with structural similarity to paraoxonase 1, another protein with lactonase and organophosphate hydrolase activities. SMP30 has recently been tied to several physiological conditions including osteoporosis, liver fibrosis, diabetes, and cancer. This review aims to describe the recent advances made toward understanding the connection between molecular structure, enzymatic activity and physiological function of this highly conserved, multifaceted protein.

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“…(3) Although the physiological function of SMP30/GNL is still not entirely clear, our studies using SMP30/GNL knockout (KO) mice have revealed that a reduction in SMP30/GNL expression may contribute to age-associated deterioration of cellular function and the enhanced susceptibility to harmful stimuli in aged tissue. (4–11) SMP30/GNL KO mice cannot synthesize ascorbic acid and display symptoms of scurvy when fed a VC-deficient diet. (3,12,13) Furthermore, SMP30/GNL KO mice have been used for the study of VC movement and regulation of VC transporter expression.…”

Section: Introductionmentioning

confidence: 99%

Pancreatic insulin release in vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice

Senmaru

Yamazaki

Okada

et al. 2012

J. Clin. Biochem. Nutr.

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We recently identified senescence marker protein-30 as the lactone-hydrolyzing enzyme gluconolactonase, which is involved in vitamin C biosynthesis. In this study, we investigated the effects of vitamin C on insulin secretion from pancreatic β-cells using senescence marker protein-30/gluconolactonase knockout mice. In intraperitoneal glucose tolerance tests, vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice demonstrated impaired glucose tolerance with significantly lower blood insulin levels at 30 and 120 min post-challenge than in wild type mice (p<0.01–0.05). In contrast, vitamin C-sufficient senescence marker protein-30/gluconolactonase knockout mice demonstrated significantly higher blood glucose and lower insulin only at the 30 min post-challenge time point (p<0.05). Senescence marker protein-30/gluconolactonase knockout mice showed enhanced insulin sensitivity regardless of vitamin C status. Static incubation of islets revealed that 20 mM glucose-stimulated insulin secretion and islet ATP production were significantly decreased at 60 min only in vitamin C-deficient SMP30/GNL knockout mice relative to wild type mice (p<0.05). These results indicate that the site of vitamin C action lies between glycolysis and mitochondrial oxidative phosphorylation, while SMP30 deficiency itself impairs the distal portion of insulin secretion pathway.

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Hepatic senescence marker protein-30 is involved in the progression of nonalcoholic fatty liver disease

Abstract: These results suggest that hepatic SMP30 is closely associated with the pathogenesis of NAFLD, although it is not known whether decreased hepatic SMP30 is a result or a cause of cirrhosis.

Cited by 41 publications

References 33 publications

Science of Nonalcoholic Fatty Liver Disease in Anti-Aging Medicine 2011

Science of Nonalcoholic Fatty Liver Disease in Anti-Aging Medicine 2011

Senescence marker protein 30: functional and structural insights to its unknown physiological function

Pancreatic insulin release in vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice

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