Fatty liver: Biochemical and clinical considerations

Am, Hoyumpa; Hl, Greene; Gd, Dunn; Schenker, Steven

doi:10.1007/bf01070758

Cited by 162 publications

(68 citation statements)

References 141 publications

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“…32 lets with an increased molar percentage of palmitic and oleic acids as it occurs in the case of an excessive dietary intake of carbohydrates. 33 Using this experimental model, we have recently documented that the oxidative balance in rat fatty livers is impaired. In particular, the total liver tissue levels of ␣-tocopherol and vitamin C were reduced and associated with increased lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: Effect of the nutritional status

et al. 2001

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Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline-deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury. Mitochondria were isolated from normal and fatty livers of fed or 18-hour fasted rats. Oxidative injury was evaluated by measuring the mitochondrial content of thiobarbituric reactive substances, protein carbonyls, glutathione, and protein sulfhydryls. The mitochondrial F 0 F 1 -ATP synthase content, tissue ATP concentration, and liver histology were also determined. Compared with normal liver, under fed conditions, fatty livers showed a greater mitochondrial content of oxidized lipids and proteins together with a low concentration of sulfhydryls and glutathione. The mitochondrial catalytic ␤-F 1 subunit of the F 0 F 1 -ATP synthase was about 35% lower in fatty livers. Hepatic ATP was also significantly reduced in fatty liver. Starvation exacerbated mitochondrial oxidative injury in both groups but to a greater extent in fatty livers. In the steatotic group, fasting induced a significant decrease of the ATP levels, which was accompanied by a 70% fall of the catalytic ␤-F 1 subunit. These data indicate that the mitochondrial oxidative alterations in fatty livers are associated with an important reduction of the F 0 F 1 -ATP synthase. These changes, which are greatly exacerbated after starvation, may account for the reduced synthesis of the hepatic ATP observed in the presence of fatty infiltration. (HEPATOLOGY 2001;33:808-815.)Hepatic steatosis without concomitant inflammation or fibrosis, is usually considered a benign condition. However, fatty degeneration increases the sensitivity of the liver to several types of injury, such as those due to ischemia-reperfusion 1 or drug toxicity. 2 Fatty infiltration is associated with a number of intracellular disorders, which can be either a cause or a consequence of lipid accumulation. 3 Among them, mitochondrial abnormalities related to an increased generation of reactive oxygen species have been described in human steatosis of various etiology (alcoholic 4 and nonalcoholic steatohepatitis, 5 iron, 6 or copper 7 overload) and in several experimental models of fatty liver, including alcohol administration 8 and drug toxicity. 2,9 Mitochondrial oxidative injury has been also described in conditions of chronic administration of commonly used drugs, such as valproate 10 or amiodarone, 11 the hepatic metabolites of which are known to interfere with mitochondrial respiration and fatty acid metabolism, thus producing fatty degeneration.Oxidative metabolism in mitochondria represent the main source of energy for the cells. Alterations of specific mitochondrial functions may, therefore, lead to an impaired production of ATP and a reduced uptake of substrates for mitochondrial metabolism 12 and eventually limit resistance and survival o...

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Section: Discussionmentioning

confidence: 99%

Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: Effect of the nutritional status

et al. 2001

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“…The IHF was calculated as previously described, 10,11,13 and absolute concentrations expressed as percent fat by weight of volume using equations validated by Longo et al 15 Traditionally, liver fat content greater than 50 mg/g (5% by wet weight and equivalent to 6.5% of ratio methylene/methylene ϩ water ϫ 100 in our setting) is diagnostic of hepatic steatosis, 16,17 and study subjects were diagnosed as individuals with normal IHF content (Ͻ5% wet weight) or higher than normal IHF content (Ͼ5% wet weight).…”

Section: Calculationsmentioning

confidence: 99%

Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver

Lattuada²,

et al. 2007

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Fatty liver is characterized by metabolic abnormalities at the liver, but also at skeletal muscle and adipose tissue sites. It is hypothesized that the heart may be suffering metabolic alterations, and this study was undertaken to ascertain whether individuals with fatty liver have left ventricular (LV) alterations of energy metabolism, structure, and function and abnormal amounts of epicardial fat as a specific marker of visceral fat accumulation. To this end we studied young, nondiabetic men matched for anthropometric features with (n ‫؍‬ 21) or without (n ‫؍‬ 21) fatty liver by means of (1) cardiac magnetic resonance imaging (MRI); (2) cardiac 31 P-MR spectroscopy (MRS); and (3) hepatic 1 H-MRS to assess quantitatively the intrahepatic fat (IHF) content. Insulin sensitivity was determined by the updated HOMA-2 computer model. Individuals with fatty liver showed reduced insulin sensitivity, increased serum free fatty acid (FFA), and Eselectin, abnormal adipokine concentrations, and higher blood pressure. LV morphology and systolic and diastolic functions were not different; however, in the scanned intrathoracic region, the intrapericardial (7.8 ؎ 3.1 versus 5.9 ؎ 2.5 cm 2 ; P < 0.05) and extrapericardial (11.7 ؎ 6.1 versus 7.8 ؎ 3.2 cm 2 ; P < 0.03) fat was increased in men with fatty liver compared with those without fatty liver. N onalcoholic fatty liver (NAFL) is a feature of the insulin resistance syndrome 1,2 and a typical aspect of body composition related to visceral adiposity. 3 Multiple metabolic abnormalities in organs and tissues under the influence of insulin were reported: impaired insulin-mediated inhibition of hepatic glucose production was reported at the liver site, 1,4 impaired insulin-stimulated glucose metabolism was shown at the level of the skeletal muscle, 1,5,6 and impaired insulin-dependent control on lipolysis was detected at the level of the adipose tissue. 1,4 The heart is another organ whose metabolism may be influenced by insulin resistance. Few insights are available about cardiac metabolism in patients with NAFL because of the difficulties of studying nonin-

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“…Diet records over a 7 d period were analysed before and after the intervention and showed a reduction in total fat intake. Visceral fat area on MRI was measured using a technique described elsewhere 19 and was seen to reduce over the 12 week treatment period. Subcutaneous fat did not signi®-cantly change.…”

Section: Methodsmentioning

confidence: 99%

“…17 Technical dif®culties associated with spectroscopy methods in patients with large amounts of either omental or visceral fat have been documented and preclude this method for patients with abdominal obesity. 18 In addition, spectroscopy is unable to detect fat in a normal liver and as this is thought to comprise up to 5% of the total liver by weight, 19 more sensitive methods are needed to enable small changes to be seen.…”

Section: Introductionmentioning

confidence: 99%

Measurement of liver fat by MRI and its reduction by dexfenfluramine in NIDDM

et al. 1997

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OBJECTIVE: To validate a variation of a well-established magnetic resonance imaging (MRI) technique to detect liver fat and use it to monitor liver fat changes after treatment with dexfen¯uramine in men with non-insulin dependent diabetes mellitus (NIDDM). DESIGN: (a) Simple correlation study of MRI Liver Fat Index with liver biopsy results; (b) Open Study of 10 men with NIDDM treated with dexfen¯uramine for 12 weeks in addition to their`usual' therapy. SUBJECTS: (a) 19 patients (3F; 16M) with abnormal liver function tests undergoing liver biopsy; (b) 10 men, Body Mass Index (BMI)`30, Waist to hip ratio (WHR) b0.90 with poorly controlled NIDDM despite oral sulphonylurea therapy. MEASUREMENTS: (a) MRI liver fat; standard liver biopsy; (b) MRI visceral fat, MRI liver fat, euglycaemic clamp, plasma lipids, fasting glucose and c-peptide levels. RESULTS: In the validation group, there was a strong relationship between the MRI Liver Fat Index and histopathological assessment of the liver biopsies (r 0.87,`0.0001). During treatment with dexfen¯uramine the mean Liver Fat Index reduced from 10.6 AE 3.4 to 6.6 AE 2.8 (P 0.05). The reduction in Liver Fat Index correlated with the reduction in visceral fat (r 0.84, P 0.001) as well as with the improvement in insulin sensitivity (r 0.62, P 0.05). Using partial correlation analysis, the relationship between the change in visceral adipose tissue and the improvement in insulin sensitivity was weaker if the Liver Fat Index was kept constant (r 0.76 decreased to r 0.56). CONCLUSIONS: In this group of subjects MRI Liver Fat Index correlated well with liver fat as seen on biopsy. The Liver Fat Index reduced after 12 weeks therapy with dexfen¯uramine suggesting a role for hepatic steatosis in the complex interaction between visceral adipose tissue and insulin sensitivity.

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Fatty liver: Biochemical and clinical considerations

Cited by 162 publications

References 141 publications

Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: Effect of the nutritional status

Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: Effect of the nutritional status

Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver

Measurement of liver fat by MRI and its reduction by dexfenfluramine in NIDDM

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