Serum Cytokeratin 18 M30 Antigen Level and Its Correlation with Nutritional Parameters in Middle-Aged Japanese Males with Nonalcoholic Fatty Liver Disease (NAFLD)

Tabuchi, Mayumi; Tomioka, Kayoko; Kawakami, Takayo; Murakami, Yasuko; Hiramatsu, Masayuki; Itoshima, Tatsuya; Sugawara, Shiori; Kawashima, Aiko; Okita, Misako; Tsukamoto, Ikuyo

doi:10.3177/jnsv.56.271

Cited by 20 publications

(18 citation statements)

References 39 publications

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“…M30 stains for keratin 18 that has been cleaved by caspase 3, hence identifying apoptotic cells (19). Recent studies have demonstrated that M30 can predict steatosis and hepatocytic injury (21)(22)(23)(24). Our results suggest that a higher concentration of OA will increase the severity of NAFLD.…”

Section: Discussionmentioning

confidence: 65%

Depending on the stage of hepatosteatosis, p53 causes apoptosis primarily through either DRAM‐induced autophagy or BAX

Lou

Wen

et al. 2013

Liver International

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Background & AimsApoptosis mediated by p53 plays a pathological role in the progression of hepatosteatosis. It is noteworthy that p53 can promote the expression of damage-regulated autophagy modulator (DRAM), an inducer of autophagy-mediated apoptosis. However, the relationship between p53-mediated apoptosis and autophagy in hepatosteatosis remains elusive. This study aimed to examine how p53 orchestrates autophagy and apoptosis to affect hepatosteatosis.MethodsHepG2 cells were treated with oleic acid (OA) for 24 h to induce hepatosteatosis. Mice were fed a high-fat diet for 20 or 40 weeks to induce hepatosteatosis.ResultsOA induced a dose-dependent increase in steatosis severity and apoptosis. OA also induced autophagy, which was a critical inducer of apoptosis in mild steatosis induced by 400 μM OA, but not in the more severe steatosis induced by 800 and 1200 μM OA. p53 inhibition by siRNA mostly blocked OA-induced apoptosis and autophagy. Moreover, OA-induced autophagy was DRAM-dependent and primarily occurred in the mitochondria (mitophagy), where DRAM was localized. In severe steatosis induced by 1200 μM OA, apoptosis was mainly dependent on p53-induced expression of BAX, which was also localized to the mitochondria. Our in vivo study showed that p53 expression increased in both mild and severe hepatosteatosis. Increased DRAM expression and autophagy were identified in mild hepatosteatosis, whereas greater BAX expression was observed in severe hepatosteatosis.Conclusionsp53 may induce apoptosis via different mechanisms. DRAM-mediated mitophagy is a primary apoptotic inducer in mild hepatosteatosis, whereas p53-induced BAX expression mainly induces apoptosis in severe hepatosteatosis.

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Section: Discussionmentioning

confidence: 65%

Depending on the stage of hepatosteatosis, p53 causes apoptosis primarily through either DRAM‐induced autophagy or BAX

Lou

Wen

et al. 2013

Liver International

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“…This was validated by the same group and in a cohort of patients who underwent bariatric surgery, an M30-cutoff value of 275 U/L was established to discriminate simple steatosis from NASH [7, 17]. We and others were able to show that M30 correlates with fatty acid transporter expression in liver tissue and specific fatty acids in the serum [18, 19]. In a cohort of patients with polycystic ovarial syndrome, we could identify a high rate of patients with NASH utilizing this assay [20].…”

Section: Discussion and Reviewmentioning

confidence: 98%

Evaluation of Biomarkers of NAFLD in a Cohort of Morbidly Obese Patients

Kälsch

Bechmann

Kälsch

et al. 2011

Journal of Nutrition and Metabolism

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Hepatocyte apoptosis is a key event in nonalcoholic fatty liver disease (NAFLD), and serum apoptotic markers are emerging as surrogate markers for NAFLD. We studied the role of caspase-cleaved cytokeratin18 in the diagnosis of fibrosis in a cohort of 127 morbidly obese patients and also performed a review of the literature biomarkers of NAFLD and fibrosis. Here, we found that cleaved caspase 18 correlated with liver steatosis and liver injury as assessed by serum transaminase levels. Furthermore, hepatocyte apoptosis as assessed by cleaved CK18 and TUNEL staining correlated with the extent of fibrosis as assessed by Sirius Red staining and serum hyaluronic acid. These results underscore the important role of hepatocyte apoptosis in the pathogenesis of fibrosis in NAFLD, which led to the utilization of surrogate markers for apoptosis in the noninvasive diagnosis of NAFLD. We furthermore reviewed current literature of biomarkers of NAFLD and fibrosis.

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“…It has been demonstrated that SFAs are potentially hepatotoxic through induction of lipoapoptosis (37). So, weight loss can prevent hepatocellular apoptosis in NAFLD through improving fatty acids metabolism (38). …”

Section: Discussionmentioning

confidence: 99%

How Much Weight Loss is Effective on Nonalcoholic Fatty Liver Disease?

et al. 2013

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BackgroundNonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide with no specific treatment. Weight loss is the most effective therapeutic strategy in its management; however, there is no consensus on its specifics. Thus, this study was conducted to evaluate the effects of weight loss on liver enzymes, markers of inflammation, oxidative stress and CK18-M30 (cytokeratin 18) as a biomarker of hepatocellular apoptosis.ObjectivesTo study the effect of weight reduction diet as an exclusive treatment for NAFLD.Patients and MethodsForty four patients with NAFLD received a diet including a 500 to 1000 kcal per day intake reduction as30% fat, 15% protein, and 55% carbohydrate for six months. Anthropometric parameters, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lipid profile, malondialdehyde (MDA), TNF-α, IL-6, CK18-M30 were measured at baseline and at the end of the study. At the end of follow up, patients were classified as adherent or nonadherent to treatment according to a weight loss of ≥ 5%, or < 5% of initial body weight, respectively.ResultsTwenty five patients were classified as adherent group and nineteen as nonadherent group (9.7% vs. 1.9% total body weight loss after 6 months, respectively). After 6 months, changes in adherent and nonadherent groups were as follows: reduction in body weight from 93.7 ± 15.8 kg to 84.2 ± 13.4 kg vs. 94 ± 16.6 kg to 92.2 ± 16.2 kg (P < 0.05), BMI from 32.7 ± 3.9 to 29.5 ± 3.2 vs.31.8 ± 5.4 to 31.1 ± 5.3 (P < 0.001), and waist circumference from 105.1 ± 12.6 cm to 97.4 ± 9.8 cm vs.106.8 ± 14.2 cm to 103.7 ± 14 cm (P < 0.001), respectively. Diastolic blood pressure was significantly decreased in adherent group (from 80.2 ± 5.1 mmHg to 76.9 ± 5 mmHg; P < 0.001). Also, total cholesterol, LDL, triglyceride, ALT, AST, GGT and CK18-M30 levels were significantly decreased in the adherent group compared to nonadherent group (P < 0.05).ConclusionsThis intervention offers a practical approach for treatment of patients with NAFLD with diet therapy.

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Serum Cytokeratin 18 M30 Antigen Level and Its Correlation with Nutritional Parameters in Middle-Aged Japanese Males with Nonalcoholic Fatty Liver Disease (NAFLD)

Cited by 20 publications

References 39 publications

Depending on the stage of hepatosteatosis, p53 causes apoptosis primarily through either DRAM‐induced autophagy or BAX

Depending on the stage of hepatosteatosis, p53 causes apoptosis primarily through either DRAM‐induced autophagy or BAX

Evaluation of Biomarkers of NAFLD in a Cohort of Morbidly Obese Patients

How Much Weight Loss is Effective on Nonalcoholic Fatty Liver Disease?

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