Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function

Valdecantos, M. Pilar; Pérez-Matute, Patricia; González‐Muniesa, Pedro; Prieto-Hontoria, Pedro L.; Moreno-Aliaga, María J.; Martínéz, J. Alfredo

doi:10.1016/j.jnutbio.2011.11.011

Cited by 48 publications

(39 citation statements)

References 63 publications

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“…Complex IV deficiencies can interrupt the process of oxidative phosphorylation, thus decreasing the production of energy for the cells to function properly. Other studies have shown the deleterious effects that the high-fat diet produced in this complex, by reducing the oxidative process [14,56,57,62]. In the HFE group, we found an increase in the oxidative process generated by supplementation with EGCG ( Figure 4).…”

Section: Accepted Manuscriptsupporting

confidence: 54%

Decaffeinated green tea extract rich in epigallocatechin-3-gallate prevents fatty liver disease by increased activities of mitochondrial respiratory chain complexes in diet-induced obesity mice

Santamarina

Carvalho-Silva

Gomes

et al. 2015

The Journal of Nutritional Biochemistry

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Nonalcoholic fatty liver disease has been considered the hepatic manifestation of obesity. It is unclear whether supplementation with green tea extract rich in epigallocatechin-3-gallate (EGCG) influences the activity of mitochondrial respiratory chain complexes and insulin resistance in the liver. EGCG regulated hepatic mitochondrial respiratory chain complexes and was capable of improving lipid metabolism, attenuating insulin resistance in obese mice. Mice were divided into four groups: control diet+water (CW) or EGCG (CE) and hyperlipidic diet+water (HFW) or EGCG (HFE). All animals received water and diets ad libitum for 16 weeks. Placebo groups received water (0.1 ml/day) and EGCG groups (0.1 ml EGCG and 50 mg/kg/day) by gavage. Cytokines concentrations were obtained by ELISA, protein expression through Western blotting and mitochondrial complex enzymatic activity by colorimetric assay of substrate degradation. HFW increased body weight gain, adiposity index, retroperitoneal and mesenteric adipose tissue relative weight, serum glucose, insulin and Homeostasis Model Assessment of Basal Insulin Resistance (HOMA-IR); glucose intolerance was observed in oral glucose tolerance test (OGTT) as well as ectopic fat liver deposition. HFE group decreased body weight gain, retroperitoneal and mesenteric adipose tissue relative weight, HOMA-IR, insulin levels and liver fat accumulation; increased complexes II-III and IV and malate dehydrogenase activities and improvement in glucose uptake in OGTT and insulin sensitivity by increased protein expression of total AKT, IRα and IRS1. We did not find alterations in inflammatory parameters analyzed. EGCG was able to prevent obesity stimulating the mitochondrial complex chain, increasing energy expenditure, particularly from the oxidation of lipid substrates, thereby contributing to the prevention of hepatic steatosis and improved insulin sensitivity.

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Section: Accepted Manuscriptsupporting

confidence: 54%

Decaffeinated green tea extract rich in epigallocatechin-3-gallate prevents fatty liver disease by increased activities of mitochondrial respiratory chain complexes in diet-induced obesity mice

Santamarina

Carvalho-Silva

Gomes

et al. 2015

The Journal of Nutritional Biochemistry

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“…Moreover, several lines of evidence suggest that toxic ROS can cause ER stress responses such as UPR [58]. Among therapies suggested for slowing disease progression, we have demonstrated the protective effect of LA co-treatment against the development of fatty liver associated with a long-term HFD feeding through the modulation ϮϮ of both mitochondrial function and lipid metabolism pathways [43]. In agreement with that, Yang et al have recently shown that co-treatment with LA in C57BL/6J mice fed with HFD reduced lipid accumulation by increasing the SIRT1/AMPK pathway [59].…”

Section: Discussionmentioning

confidence: 86%

“…Metabolic parameters (body weight gain, WAT and liver weight, liver triglyceride content, plasma triglyceride and free fatty acids) were determined as previously described [33,34,42,43].…”

Section: Reagentsmentioning

confidence: 99%

Essential role of Nrf2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes

Valdecantos

Prieto-Hontoria

Pardo

et al. 2015

Free Radical Biology and Medicine

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“…Increased hepatic mitochondrial oxidation has been observed in patients and rodents with fatty liver [23,24], which likely reflects a metabolic adaptation to elevated lipid burden to limit further fat accumulation. Indeed, the development of fatty liver and hepatic insulin resistance in response to high-fat feeding in rats can be prevented by increasing mitochondrial β-oxidation [25][26][27][28]. Furthermore, a primary defect in mitochondrial β-oxidation capacity in mice has been shown to result in liver steatosis and hepatic insulin resistance [29].…”

Section: Discussionmentioning

confidence: 99%

Protein kinase STK25 controls lipid partitioning in hepatocytes and correlates with liver fat content in humans

et al. 2015

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Aims/hypothesis Type 2 diabetes is closely associated with pathological lipid accumulation in the liver, which is suggested to actively contribute to the development of insulin resistance. We recently identified serine/threonine protein kinase 25 (STK25) as a regulator of liver steatosis, whole-body glucose tolerance and insulin sensitivity in a mouse model system. The aim of this study was to assess the role of STK25 in the control of lipid metabolism in human liver. Methods Intracellular fat deposition, lipid metabolism and insulin sensitivity were studied in immortalised human hepatocytes (IHHs) and HepG2 hepatocellular carcinoma cells in which STK25 was overexpressed or knocked down by small interfering RNA. The association between STK25 mRNA expression in human liver biopsies and hepatic fat content was analysed.Results Overexpression of STK25 in IHH and HepG2 cells enhanced lipid deposition by suppressing β-oxidation and triacylglycerol (TAG) secretion, while increasing lipid synthesis. Conversely, knockdown of STK25 attenuated lipid accumulation by stimulating β-oxidation and TAG secretion, while inhibiting lipid synthesis. Furthermore, TAG hydrolase activity was repressed in hepatocytes overexpressing STK25 and reciprocally increased in cells with STK25 knockdown. Insulin sensitivity was reduced in STK25-overexpressing cells and enhanced in STK25-deficient hepatocytes. We also found a statistically significant positive correlation between STK25 mRNA expression in human liver biopsies and hepatic fat content. Conclusions/interpretation Our data suggest that STK25 regulates lipid partitioning in human liver cells by controlling TAG synthesis as well as lipolytic activity and thereby NEFA release from lipid droplets for β-oxidation and TAG secretion. Our findings highlight STK25 as a potential drug target for the prevention and treatment of type 2 diabetes.

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Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function

Cited by 48 publications

References 63 publications

Decaffeinated green tea extract rich in epigallocatechin-3-gallate prevents fatty liver disease by increased activities of mitochondrial respiratory chain complexes in diet-induced obesity mice

Decaffeinated green tea extract rich in epigallocatechin-3-gallate prevents fatty liver disease by increased activities of mitochondrial respiratory chain complexes in diet-induced obesity mice

Essential role of Nrf2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes

Protein kinase STK25 controls lipid partitioning in hepatocytes and correlates with liver fat content in humans

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