A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease

Tovoli, Francesco; Napoli, Lucia; Negrini, Giulia; D’Addato, Sergio; Tozzi, Giulia; D’Amico, Jessica; Piscaglia, Fabio; Bolondi, Luigi

doi:10.3390/ijms18061134

Cited by 33 publications

(27 citation statements)

References 20 publications

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“…These findings confirm the results from previous studies showing a significant reduction of LAL activity in NAFLD patients, compared to HS, with a further reduction in the subgroup of those with NASH . In particular, patients with NAFL had a 27.0% reduction in LAL activity, which increased to 41.8% in the subgroup of patients with biopsy‐proven NASH.…”

Section: Discussionsupporting

confidence: 90%

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Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Baratta

Pastori

Tozzi

et al. 2019

Liver International

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Background and Aims Recent evidence showed a reduced activity of the lysosomal acid lipase (LAL) in patients with non‐alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC). However, the relationship between LAL activity and liver fibrosis has never been investigated. Methods Cross‐sectional study including 575 outpatients referred for the management of cardio‐metabolic and liver disease. The absence of liver fibrosis was defined by a FIB‐4 < 1.30 and NAFLD fibrosis score (NFS) <−1.455. LAL activity was measured with dried blood spot technique. Results Overall, 515 patients had a diagnosis of NAFLD (454 NAFL and 61 biopsy‐proven NASH) and 60 of CC. The value of LAL activity progressively decreased from healthy subjects to NAFL/NASH patients to CC (P < .001). LAL activity was reduced by 10% in patients with NAFL, by 20% in NASH and by 50% in CC. The prevalence of CC decreased across the tertiles of LAL activity: 22.2% in the lowest, 4.6% in the intermediate and 0.5% in the highest tertile. In NAFLD patients, 69.9% had a FIB4 < 1.30, and 43.1% a NFS <−1.455. Multivariate logistic regression analysis showed that Log (LAL activity) was associated with FIB‐4 < 1.30 (Odds ratio [OR] 2.19 95% confidence interval [CI] 1.33‐3.62, P = .002) and NFS < −1.455 (OR 2.43, 95% CI 1.51‐3.91, P < .001) after adjustment for confounding factors. Conclusions We found a progressive reduction of LAL activity according to liver disease severity. LAL activity was inversely associated with markers of liver fibrosis in patients with NAFLD.

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Section: Discussionsupporting

confidence: 90%

“…Previous studies showed a progressive decrease in LAL activity from healthy subjects (HS) to subjects with NAFL and those with biopsy‐proven NASH . More recently, in patients with cryptogenic cirrhosis (CC), a further reduction in the activity of LAL has been described .…”

Section: Introductionmentioning

confidence: 98%

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Baratta

Pastori

Tozzi

et al. 2019

Liver International

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“…More recently, Tovoli et al[31] performed a study of LAL activity in 81 patients with a diagnosis of NAFLD and 78 matched controls with HCV-related liver disease. LAL activity was significantly reduced in NAFLD compared to that in HCV patients, suggesting that NAFLD is characterized by a specific deficit in LAL activity.…”

Section: Lal Activity Reduction and Nafldmentioning

confidence: 99%

Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Baratta

Pastori

Ferro

et al. 2019

WJG

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Lysosomal acid lipase (LAL) plays a key role in intracellular lipid metabolism. Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage, as observed in two recessive autosomal genetic diseases, Wolman disease and Cholesterol ester storage disease. Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency. By contrast, few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene. In the last few years, a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease (NAFLD), suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease. Patients with NAFLD show a significant, progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis. Among cirrhosis of different etiologies, those with cryptogenic cirrhosis show the most significant reductions of LAL activity. These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD. Moreover, the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.

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“…They found a significant reduction in LAL activity in NAFLD patients and the enzyme activity was significantly worse in the subgroup of patients with biopsy-proven non-alcoholic steatohepatitis (NASH). More recently, Tovoli et al [18] demonstrated that this deficiency is specific to NAFLD by comparing NAFLD patients with HCV-infected patients, particularly in the pre-cirrhotic stage of disease.…”

Section: Introductionmentioning

confidence: 99%

Lysosomal Acid Lipase as a Molecular Target of the Very Low Carbohydrate Ketogenic Diet in Morbidly Obese Patients: The Potential Effects on Liver Steatosis and Cardiovascular Risk Factors

Ministrini

Calzini

Migliola

et al. 2019

JCM

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A very low carbohydrate ketogenic diet (VLCKD) is an emerging technique to induce a significant, well-tolerated, and rapid loss of body weight in morbidly obese patients. The low activity of lysosomal acid lipase (LAL) could be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is a common feature in morbidly obese patients. Fifty-two obese patients suitable for a bariatric surgery intervention underwent a 25-day-long VLCKD. The biochemical markers of glucose and lipid metabolism, and flow-mediated dilation (FMD) of the brachial artery were measured before and after VLCKD. LAL activity was measured using the dried blood spot technique in 20 obese patients and in a control group of 20 healthy, normal-weight subjects. After VLCKD, we observed a significant reduction in body mass index, fasting glucose, insulinemia, and lipid profile parameters. No significant variation in FMD was observed. The number of patients with severe liver steatosis significantly decreased. LAL activity significantly increased, although the levels were not significantly different as compared to the control group. In conclusion, VLCKD induces the activity of LAL in morbidly obese subjects and reduces the secretion of all circulating lipoproteins. These effects could be attributed to the peculiar composition of the diet, which is particularly poor in carbohydrates and relatively rich in proteins.

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A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease

Cited by 33 publications

References 20 publications

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Lysosomal Acid Lipase as a Molecular Target of the Very Low Carbohydrate Ketogenic Diet in Morbidly Obese Patients: The Potential Effects on Liver Steatosis and Cardiovascular Risk Factors

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