Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress

Jaiswal, Natasha; Maurya, Chandan Kumar; Arha, Deepti; Avisetti, Deepa R.; Prathapan, A.; Raj, P. Salin; Raghu, Kozhiparambil Gopalan; Kalivendi, Shasi V.; Tamrakar, Akhilesh K.

doi:10.1007/s10495-015-1128-y

Cited by 67 publications

(63 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The damage to hepatic mitochondrial integrity and mtDNA repair and replication mechanisms due to the fructose-rich diet could therefore lead to liver dysfunction, and consequently to metabolic diseases. Interestingly, it has been recently shown that exposure of skeletal muscle cells to fructose elicited damage similar to that found here by us in the liver, namely it increased oxidative stress and mitochondrial dysfunction, as well as decreased mitochondrial DNA content [37]. In contrast, Yamazaki et al [38] found increased mitochondrial gene expression and mtDNA content in the liver of rats fed with fructose-containing drinking water.…”

Section: Discussionsupporting

confidence: 67%

Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats

et al. 2017

View full text Add to dashboard Cite

Evidence indicates that many forms of fructose-induced metabolic disturbance are associated with oxidative stress and mitochondrial dysfunction. Mitochondria are prominent targets of oxidative damage; however, it is not clear whether mitochondrial DNA (mtDNA) damage and/or its lack of repair are events involved in metabolic disease resulting from a fructose-rich diet. In the present study, we evaluated the degree of oxidative damage to liver mtDNA and its repair, in addition to the state of oxidative stress and antioxidant defense in the liver of rats fed a high-fructose diet. We used male rats feeding on a high-fructose or control diet for eight weeks. Our results showed an increase in mtDNA damage in the liver of rats fed a high-fructose diet and this damage, as evaluated by the expression of DNA polymerase γ, was not repaired; in addition, the mtDNA copy number was found to be significantly reduced. A reduction in the mtDNA copy number is indicative of impaired mitochondrial biogenesis, as is the finding of a reduction in the expression of genes involved in mitochondrial biogenesis. In conclusion, a fructose-rich diet leads to mitochondrial and mtDNA damage, which consequently may have a role in liver dysfunction and metabolic diseases.

show abstract

Section: Discussionsupporting

confidence: 67%

Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Fructose-induced ER stress activation has been linked to the activation of SREBP-1c, associated with the upregulation of lipogenic enzymes genes, with downstream effect on insulin sensitivity 92,119 . High-fructose or sucrose diet can also results in CHOP upregulation and JNK activation 120,121 , which further induce cellular apoptosis subsequent to BH3-only proteins BIM and PUMA-mediated mitochondrial dysfunction and caspase 3 activation 122 and glucose can further amplify FA-induced ER stress 123 (Table 1). …”

Section: ) Harmful Effects Of Hepatotoxic Carbohydratesmentioning

confidence: 99%

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

et al. 2016

View full text Add to dashboard Cite

The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance in tissues. In this review, we highlight the lipids and carbohydrates that provoke hepatocyte injury and the mechanisms involved in lipotoxicity and glucotoxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment. Through upregulation of proteins involved in various pathways including PKR-like ER kinase (PERK), CCAAT/enhancer-binding homologous protein (CHOP), c-Jun NH2-terminal kinase-1 (JNK), Bcl-2 interacting mediator (BIM), p53 upregulated modulator of apoptosis (PUMA), and eventually caspases, hepatocytes in lipotoxic states ultimately undergo apoptosis. The protective role of certain lipids and possible targets for pharmacological therapy are explored. Finally, we discuss the role of high fructose and glucose diets in contributing to organelle impairment and poor glucose transport mechanisms, which perpetuate hyperglycemia and hyperlipidemia by shunting of excess carbohydrates into lipogenesis.

show abstract

“…In different tissues of fructose-fed animals, mitochondrial dysfunction is detected, characterized by increased mitochondrial mass [62,63], decreased mitochondrial electron transport capacity [62,63], loss of mitochondrial membrane potential [64] and disturbance of antioxidant defense [32]. In turn, insulin resistance affects FFA-mediated mitochondrial uncoupling [65].…”

Section: Direct Dangerous Factors Under High Fructose Consumptionmentioning

confidence: 99%

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

2017

View full text Add to dashboard Cite

High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

show abstract

Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress

Cited by 67 publications

References 56 publications

Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats

Fructose-Rich Diet Affects Mitochondrial DNA Damage and Repair in Rats

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

Contact Info

Product

Resources

About