Adaptation of Hepatic Mitochondrial Function in Humans with Non-Alcoholic Fatty Liver Is Lost in Steatohepatitis

Koliaki, Chrysi; Szendroedi, Julia; Kaul, Kirti; Jeleník, Tomáš; Nowotny, Peter; Jankowiak, Frank; Herder, Christian; Carstensen, Maren; Krausch, M.; Knoefel, Wolfram Trudo; Schlensak, Matthias; Roden, Michael

doi:10.1016/j.cmet.2015.04.004

Cited by 802 publications

(928 citation statements)

References 34 publications

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“…In perfused livers, where oxygen consumption was measured directly, these pathways consumed roughly 40% of hepatic energy production (Table 3), which is very similar to the estimate made by Landau in human liver (16). Hence, individuals with a 60% increase in GNG (2) should have a roughly 30% nic oxygen consumption was increased by 45% in obese subjects, suggesting increased respiration (39), and more recently, mitochondrial respiration was found to be increased in obese humans (40). A uniform conclusion about β-oxidation is similarly difficult to ascertain across studies.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

Satapati¹,

Kucejová²,

Duarte³

et al. 2015

Journal of Clinical Investigation

343

249

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Section: Discussionmentioning

confidence: 99%

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

Satapati¹,

Kucejová²,

Duarte³

et al. 2015

Journal of Clinical Investigation

343

249

View full text Add to dashboard Cite

“…14 This may reflect an adaptation to increased lipid availability to protect from further accumulation of hepatic lipids. 15 But why do portal FFA levels remain increased 8 weeks after stopping short-term HFD? It was previously suggested that increased adipose tissue lipolysis is an important source of FFA promoting hepatic lipid accumulation.…”

Section: Discussionmentioning

confidence: 99%

A short bout of HFD promotes long-lasting hepatic lipid accumulation

et al. 2015

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A short bout of high fat diet (HFD) impairs glucose tolerance and induces hepatic steatosis in mice. Here, we aimed to elaborate on long-lasting effects of short-term high fat feeding. As expected, one week of HFD significantly impaired glucose tolerance. Intriguingly, recovery feeding with a standard rodent diet for 8 weeks did not fully normalize glucose tolerance. In addition, mice exposed to a short bout of HFD revealed significantly increased liver fat accumulation paralleled by elevated portal free fatty acid levels after 8 weeks of recovery feeding compared to exclusively chow-fed littermates. In conclusion, a short bout of HFD has long-lasting effects on hepatic lipid accumulation and glucose tolerance.

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“…Hepatic triacylglycerol accumulation is accompanied by abnormal hepatic energy metabolism [46] and impaired insulin-mediated suppression of hepatic glucose and very lowdensity lipoprotein production [47] , leading to hyperglycaemia, hypertriglyceridaemia and hyperinsulinaemia. In non-diabetic persons, the product of fasting glucose (in mmol/l) and insulin (in mU/ml), divided by 22.5 (HOMA-IR) can serve as surrogate for IR [48] , and is therefore an acceptable alternative to more expensive and time-consuming dynamic testing.…”

Section: Common Metabolic Disorders Related To Nafldmentioning

confidence: 99%

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

2016

Journal of Hepatology

3,534

1,817

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DefinitionNAFLD is characterised by excessive hepatic fat accumulation, associated with insulin resistance (IR), and defined by the presence of steatosis in >5% of hepatocytes according to histological analysis or by the proton density fat fraction (PDFF, providing a rough estimation of the volume fraction of fatty material in the liver) >5.6% assessed by proton magnetic resonance spectroscopy ( 1 H-MRS) or quantitative fat/water selective magnetic resonance imaging (MRI). NAFLD includes two pathologically distinct conditions with different prognoses: nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH); the latter covers a wide spectrum of disease severity, including fibrosis, cirrhosis and hepatocellular carcinoma (HCC) ( table 2 ).The diagnosis of NAFLD requires exclusion of both secondary causes and a daily alcohol consumption ≥ 30 g for men and 20 g for women [1] . The relationship between alcohol and liver injury depends on several cofactors (type of alcoholic beverage, drinking patterns, duration of exposure, individual/genetic susceptibility), rendering simple quantitative thresholds at least partly arbitrary. Specifically, patients consuming moderate amounts of alcohol may be still predisposed to NAFLD if they have metabolic risk factors. Of note, the overall impact of metabolic risk factors on the occurrence of steatosis appears to be higher than that of alcohol in these patients [3] . The definitive diagnosis of NASH requires a liver biopsy. Recommendations• Patients with IR and/or metabolic risk factors (i.e., obesity or metabolic syndrome (MetS)) should undergo diagnostic procedures for the diagnosis of NAFLD, which relies on the demonstration of excessive liver fat (A1) • Individuals with steatosis should be screened for secondary causes of NAFLD, including a careful assessment of alcohol intake. The interaction between moderate amounts of alcohol and metabolic factors in fatty liver should always be considered (A1) • Other chronic liver diseases, that may coexist with NAFLD, should be identified as this might result in more severe liver injury (B1) Prevalence and IncidenceNAFLD is the most common liver disorder in Western countries, affecting 17-46% of adults, with differences according to the diagnostic method, age, sex and ethnicity [4] . It parallels the prevalence of MetS and its components, which also increases the risk of more advanced disease, both in adults and in children. NAFLD is also present in 7% of normalweight (lean) persons [5] , more frequently in females, at a younger age and with normal liver enzymes. Their liver disease may nonetheless be progressive [6] .NAFLD incidence has rarely been measured. It was 20-86/1,000 person-years based on elevated liver enzymes and/or on ultrasound (US), and 34/1,000 per year by 1 H-MRS [7] . The need for NAFLD screening in the community has been questioned given the high direct and indirect costs of testing, the low predictive value of non-invasive tests, the risks of liver biopsy and the lack of effective treatments [8] . Ho...

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Adaptation of Hepatic Mitochondrial Function in Humans with Non-Alcoholic Fatty Liver Is Lost in Steatohepatitis

Cited by 802 publications

References 34 publications

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

A short bout of HFD promotes long-lasting hepatic lipid accumulation

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

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