The prevalence of the metabolic syndrome, a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder consists of a cluster of metabolic conditions, such as hypertriglyceridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that-in combination with genetic susceptibility and abdominal obesity are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart diseases.1
One of the defects in metabolic syndrome and its associated diseases is mitochondrial dysfunction. Changes in the mitochondrial membrane potential, a reduction in the ATP level, the inhibition of mitochondrial oxygen consumption and reduced mitochondrial biogenesis2 are some of the characteristics of mitochondrial dysfunction.3
The underlying mechanism of mitochondrial dysfunction is very complex, with genetic factors from both nuclear and mitochondrial genomes and numerous environmental factors.4 In addition to these factors, excessive formation of reactive oxygen species (ROS) in obesity and Type 2 Diabetes Mellitus5 contributes to mitochondrial dysfunction, while at physiological levels ROS participate in intracellular signaling and regulation as "redox messengers." Reactive oxygen species generated by mitochondria, or from other sites within or outside the cell, cause damage to mitochondrial components and initiate degradative processes. Such toxic reactions contribute significantly to the aging process. Furthermore, when mitochondrial autphagy is compromised, oxidized proteins acucumulate and cellular respiration and insulin secretion decrease.6
Currently, mitochondria remain an attractive and pertinent target for the prevention and treatment of metabolic disorders.7
1. Bonomini F., Rodella L. F., and Rezzani R. Metabolic Syndrome, Aging and Involvement of Oxidative Stress. Aging Dis. 2015; 6(2): 109–120.
2. Ren J., Pulakat L., Whaley-Connell A., and Sowers J. R. Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease. J. Mol. Med. 2010; 88: 993–1001.
3. Pieczenik S. R., and Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp. Mol. Pathol. 2007; 83: 84–92.
4. Lee H. K., Cho Y. M., Kwak S. H., Lim S., Park K. S., and Shim E. B. Mitochondrial dysfunction and metabolic syndrome-looking for environmental factors. Biochim. Biophys. Acta 2010; 1800: 282–289.
5. Chattopadhyay M., Khemka V. K., Chatterjee G., Ganguly A., Mukhopadhyay S., and Chakrabarti S. Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects. Mol. Cell. Biochem. 2015; 399: 95–103.
6. Soleimanpour S. A., Gupta A., Bakay M., Ferrari A. M., Groff D. N., Fadista J., Spruce L. A., Kushner J. A., Groop L., Seeholzer S. H., Kaufman B. A., Hakonarson H., and Stoffers D. A. The diabetes susceptibility gene Clec16a regulates mitophagy. Cell. 2014; 157(7): 1577-1590.
7. Litvinova L., Atochin D. N., Fattakhov N., Vasilenko M., Zatolokin P., and Elena Kirienkova. Nitric oxide and mitochondria in metabolic syndrome. Front Physiol. 2015; 6: 20.
All our assays are fully customizable and can be adapted to meet your specific needs.
Contact us to learn how our technologies might be of value to you!
Which technologies to use
Acoholic and non-alcoholic liver steatosis models have been developed in HepG2 cells, and are available for all our technologies.
BBS or BBS + package
ICDD's Bioenergetic Balance Screen (BBS/BBS+) helps you get a finer understanding of your drug's mechanism of action at the mitochondrial level, and evaluate your compound's impact on β-oxidation, oxidative phosphorylation (OXPHOS) and the tricarboxylic (TCA) cycle.
The BBS/BBS+ packages are the multiplexed and integrated measurements, in a same cell, of:
- Oxygen consumption
- ATP production
- Glycolysis level
- Cell viability
- TCA cycle turning (BBS+ only)
The BBS package is available in HTS/single point or dose response studies.
Our Redox balance, avalaible in HTS/dose response studies, is the measurement of (any or all):
- ROS mitochondrial production
- Cytoplasm ROS accumulation
- MnSOD Cu/ZnSOD activities
- Catalase activity
- Total GSH activity
- Lipid peroxidation level (TBARS)
- Protein carbonylation
- Cell viability
mtDNA content and quality control
Use our technologies to assess:
- Changes in mitochondrial mtDNA content, which have been reported in a broad range of diseases and is a pertinent target in diabetes and obesity.
- Mitochondrial autophagy
Mitophagy is the selective degradation of mitochondria by autophagy. ICDD provides image analyses to quantify this phenomenon.
- Quantitative analysis of mitochondrial proteins or of proteins modulating mitochondrial functions.
Mitochondrial membrane permeability assay
Mitochondrial membrane permability is a classical outcome for mitochondria-mediated apoptosis.