Hello readers! After some deadlines, experiments and new exciting collaborations, I am back to tell you more about adipose tissues and their characteristics. Today I will write about mitochondria and why this organelle is so important, especially for our brown adipose tissue.
“impairment of mitochondrial functions in adipocytes can have whole body pathological consequences”
We already know that brown adipose tissue is capable of generating heat by consuming large amounts of substrates. Uncoupling protein 1 (UCP1), a protein present in the inner mitochondrial membrane, is responsible for heat generation, since it uncouples ATP production and, instead, energy is released as heat. As you can imagine, mitochondrial content is a very important characteristic of brown adipose tissue, and in fact is one of the main differences among adipocyte types. As we know, there are 3 types of adipocytes; white, beige and brown, depending on their mitochondrial content (highest in BAT) and the size of their lipid droplets. It has been described that defects in adipocyte mitochondria may play a role in the development of obesity and diabetes. But, what is a mitochondrion and why is it so important?
Mitochondria: the powerhouse of the cell
Mitochondria are cellular organelles present in eukaryotic organisms (thus, not present in Bacteria or Archaea). They have a size of 0.75 – 3 µm and comprise six compartments: outer membrane, inner membrane, intermembrane space, cristal membranes, intracristal space and protein rich matrix. They are present in all human cells except from red blood cells. Their principal role in metabolism is energy production through the synthesis of ATP (95% of all cellular ATP is produced by mitochondria), and that is why mitochondria are also known as the powerhouse of the cell. However, these organelles are also involved in other crucial metabolic processes including the oxidation of fatty acids and amino acid degradation. Due to their important biological function, mitochondria are essential for the maintenance of normal physiological function of tissue cells, and mitochondrial dysfunction can cause pathological changes in the human body.
Now that we know that mitochondria are in charge of energy production in cells through substrate consumption, and that these organelles harbor UCP1 in brown and beige adipocytes, it is clear why their number and morphology are so important for adipose tissue physiological function. In fact, mitochondria in brown and beige adipocytes are more numerous, bigger in size and contain more cristae than in white ones. But not only their number and shape change. Also significant differences in mitochondrial gene expression can be found when white and brown adipocytes are compared, being BAT mitochondria more similar to their counterparts in muscle cells.
Since mitochondria are responsible for energy production in cells, we can imagine that impairment of their function will lead to pathological consequences, especially in those tissues with a high energy demand. In fact, some studies provide evidence that impairment of mitochondrial functions in adipocytes can have whole body pathological consequences.
Mitochondrial dysfunction can result from a decrease in mitochondrial biogenesis, reduced mitochondrial content and/or a decrease in their protein content. Regarding to adipose tissue, the reasons for such dysfunction point towards (1) oxidative stress, (2) insulin resistance, (3) genetic factors and (4) sedentary life. Although little can be done with our inherited predisposition to suffer from mitochondrial malfunction, oxidative stress and insulin resistance (diabetes) are usually linked to fat accumulation (obesity), which is often the result of a sedentary lifestyle. Again, exercise training emerges as a powerful tool to combat disease. It is known that physical activity is a major regulator of mitochondrial function in muscle cells, and inactivity is associated with reduced mitochondrial function and number. In the case of adipose tissues, regular exercise training has been linked to the conversion of white adipocytes into brown (beige) ones, and an increased expression of mitochondrial proteins.
In conclusion, mitochondrial health and number seem to be key factors in the onset or progression of cardiometabolic diseases such as obesity and diabetes. Then, it becomes clear that this organelle is a potential therapeutic target. Enhancing mitochondrial activity, number and size can lead to beneficial effects in several tissues.
The question now is, how can we boost our mitochondria? Is that possible? Well…that is another story…
Cedikova M. et al. 2016. Mitochondria in white, brown and beige adipocytes. Stem Cells Int. 2016:6067349
Yin X. et al. 2014. Adipocyte mitochondrial function is reduced in human obesity independent of fat cell size. J Clin Endocrinol Metab. 99(2):E209-16
Boudina S. and Graham T.E. 2014. Mitochondrial function/dysfunction in white adipose tissue. Exp Physiol. 99(9):1168-78