Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level

Sookoian, Silvia; Castaño, Gustavo Osvaldo; Scian, Romina; Gianotti, Tomás Fernández; Dopazo, Hernán; Rohr, Cristian Oscar; Gaj, Graciela; Martino, Julio San; Sevic, Ina; Flichman, Diego Martín; Pirola, Carlos José

doi:10.3945/ajcn.115.118695

Cited by 98 publications

(108 citation statements)

References 39 publications

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“…Recently, it has been suggested that increased serum aminotransferase activities in patients with NAFLD might indicate metabolic adaptation of the liver to the fat overload rather than hepatic injury (25). Hence, it is not surprising that although both PNPLA3 and TM6SF2 polymorphisms were associated in our patients with NAFLD with increased liver functions tests, analyses of liver biopsy results demonstrate their different involvement in steatosis and fibrosis.…”

Section: Fig 2 Box-and-whisker Plots Illustrating Liver Function Tementioning

confidence: 65%

Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study

Krawczyk

Rau

Schattenberg

et al. 2017

Journal of Lipid Research

174

154

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Section: Fig 2 Box-and-whisker Plots Illustrating Liver Function Tementioning

confidence: 65%

Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study

Krawczyk

Rau

Schattenberg

et al. 2017

Journal of Lipid Research

174

154

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“…Plasma activity of aspertate aminotransferase (AST) was also significantly ( P < 0.05) elevated in response to CORT challenge in both Control and Betaine groups (Fig. 2E), which indicates liver injury and metabolic adaptation35. In contrast, alanine aminotransferase (ALT), another plasma index for liver functionality, was not affected by CORT, yet significantly decreased ( P < 0.05) in betaine groups (Fig.…”

Section: Resultsmentioning

confidence: 86%

In ovo injection of betaine alleviates corticosterone-induced fatty liver in chickens through epigenetic modifications

Sun

Liu

et al. 2017

Sci Rep

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Betaine alleviates high-fat diet-induced fatty liver and prenatal betaine programs offspring hepatic lipid metabolism. Excessive corticosterone (CORT) exposure causes fatty liver in chickens, yet it remains unknown whether and how prenatal betaine modulates the susceptibility of CORT-induced fatty liver later in life. In this study, fertilized eggs were injected with saline or betaine before incubation, and the hatchlings were raised at 8 weeks of age followed by 7 days of subcutaneous CORT injection. CORT-induced fatty liver was less severe in betaine-treated chickens, with significantly reduced oil-red staining and hepatic triglyceride content (P < 0.05). The protective effect of prenatal betaine was associated with significantly up-regulated expression of PPARα and CPT1α, as well as mitochondrial DNA (mtDNA)-encoded genes (P < 0.05). Moreover, betaine rescued CORT-induced alterations in methionine cycle genes, which coincided with modifications of CpG methylation on CPT1α gene promoter and mtDNA D-loop regions. Furthermore, the elevation of hepatic GR protein content after CORT treatment was significantly reduced (P < 0.05), while the reduction of GR binding to the control region of affected genes was significantly increased (P < 0.05), in betaine-treated chickens. These results indicate that in ovo betaine injection protects the juvenile chickens from CORT-induced fatty liver.

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“…The most common tests to evaluate the degree of liver injury or liver disease are alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (Kang, 2013; Thapa and Walia, 2007). Growing evidence suggests that ALT/AST levels can be considered biomarkers of liver metabolic function, which may be indicative of a normal response to high fat intake or liver damage, including NAFLD (Jadaho et al, 2004; Kechagias et al, 2008; Sookoian et al, 2016; Sookoian and Pirola, 2012). The AST/ALT ratio represents the time course and disease aggressiveness that can be predicted from the relatively short half-life of AST (18 h), as compared to ALT (36 h) (Botros and Sikaris, 2013).…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in COL13A1, ADIPOQ and SAMM50 , in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population

Larrieta‐Carrasco

Flores

Macías-Kauffer

et al. 2018

Experimental and Molecular Pathology

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Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls. The rs2896019, rs12483959, and rs3810622 SNPs in PNPLA3 and rs1227756 in COL13A1 were associated with elevated alanine aminotransferase (ALT, ≥40 IU/L). A polygenic risk score (PRS) based on six SNPs in the ADIPOQ, COL13A1, PNPLA3, and SAMM50 genes was also associated with elevated ALT. Individuals carrying 9–12 risk alleles had 65.8% and 48.5% higher ALT and aspartate aminotransferase (AST) levels, respectively, than those with 1–4 risk alleles. The PRS showed the greatest risk of elevated ALT levels, with a higher level of significance than the individual variants. Our findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. This is the first study to examine high-density single nucleotide screening for genetic variations in a Mexican-Mestizo population. The extent of the effect of these variations on the development and progression of NAFLD in Latino populations requires further analysis.

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Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level

Cited by 98 publications

References 39 publications

Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study

Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study

In ovo injection of betaine alleviates corticosterone-induced fatty liver in chickens through epigenetic modifications

Genetic variants in COL13A1, ADIPOQ and SAMM50 , in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population

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