Peroxisomes compensate hepatic lipid overflow in mice with fatty liver

Knebel, Birgit; Hartwig, Sonja; Haas, Jutta; Goeddeke, Simon; Susanto, F.; Bohne, Lothar; Shvero, Jacob; Koellmer, Cornelia; Nitzgen, Ulrike; Müller‐Wieland, Dirk; Kotzka, Jörg

doi:10.1016/j.bbalip.2015.03.003

Cited by 32 publications

(47 citation statements)

References 42 publications

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“…There is very limited data on the role of peroxisomes in NAFLD. A few studies suggested an increased peroxisome content in NAFLD [46,48], indicating that the loss of peroxisomes is specific for malnutrition-related steatosis.…”

Section: Discussionmentioning

confidence: 98%

Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction

Zutphen

Čiapaitė

Bloks

et al. 2016

Journal of Hepatology

156

125

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Section: Discussionmentioning

confidence: 98%

Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction

Zutphen

Čiapaitė

Bloks

et al. 2016

Journal of Hepatology

156

125

View full text Add to dashboard Cite

show abstract

“…Therefore, even a small reduction in the abundance of trifunctional protein could slow down mitochondrial fatty acid oxidation and limit the acetyl-CoA pool. Additionally, some peroxisomal fatty acid oxidation enzymes were also reduced, which has been associated with hepatic fat accumulation in the past (Gambino et al, 2011;Knebel et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice

et al. 2016

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Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging society with an urging medical need for a better understanding of the underlying mechanisms. Mitochondrial fatty acid oxidation and mitochondrial‐derived reactive oxygen species (ROS) are considered critical in the development of hepatic steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD development. We therefore analyzed functional characteristics of hepatic mitochondria and associated alterations in the mitochondrial proteome in response to high fat feeding in adolescent, young adult, and middle‐aged mice. Susceptibility to diet‐induced obesity increased with age. Young adult and middle‐aged mice developed fatty liver, but not adolescent mice. Fat accumulation was negatively correlated with an age‐related reduction in mitochondrial mass and aggravated by a reduced capacity of fatty acid oxidation in high fat‐fed mice. Irrespective of age, high fat diet increased ROS production in hepatic mitochondria associated with a balanced nuclear factor erythroid‐derived 2 like 2 (NFE2L2) dependent antioxidative response, most likely triggered by reduced tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly influenced mitochondrial function by reducing mitochondrial mass, thus exacerbating diet‐induced fat accumulation. Therefore, consideration of age in metabolic studies must be emphasized.

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“…Mitochondria and peroxisomes are closely related organelles and play major roles in various hepatic metabolic functions including fatty acid oxidation (FAO) and ROS scavenging, and dysfunction in these organelles is linked to NAFLD [91011]. Peroxisome is an essential organelle for lipid metabolism because it breakdowns fatty acid with carbon chains longer than 22 through β-oxidation and degrade branched-chain fatty acids, which cannot be oxidized in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Endogenous catalase delays high-fat diet-induced liver injury in mice

Piao

Choi

Kwon

et al. 2017

Korean J Physiol Pharmacol

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Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and PGC1α mRNA expression were decreased in both CKO and WT mice at HFD feeding, GSK3β phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

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Peroxisomes compensate hepatic lipid overflow in mice with fatty liver

Cited by 32 publications

References 42 publications

Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction

Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice

Endogenous catalase delays high-fat diet-induced liver injury in mice

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