Mitochondrial potassium channels play a crucial role in regulating heat production in brown adipose tissue, opening up new possibilities for obesity treatments. A recent study by researchers at the Center for Redox Processes in Biomedicine (Redoxoma) has uncovered the involvement of ATP-sensitive mitochondrial potassium channels (MitoKATP) in both the development of brown fat cells and the activation of mitochondrial uncoupling, a process that dissipates energy as heat. This discovery is significant as it reveals a previously unknown component of thermogenic activation.
Osvaldo Rodrigues Pereira Júnior, a researcher at Redoxoma, explains, "For brown fat cells to produce heat efficiently, the mitochondrial potassium channel must be closed. This is the first time this phenomenon has been reported, and it highlights a previously unknown aspect of thermogenic activation."
Brown adipose tissue, or brown fat, is a key player in maintaining body temperature in mammals by generating heat through non-shivering thermogenesis. It consumes a significant amount of energy, making it an attractive target for obesity treatments. Understanding how brown fat is activated could lead to new methods for regulating energy expenditure and promoting metabolic health.
Pereira Júnior conducted the study during his master's degree at the Energy Metabolism Laboratory at IQ-USP, under the guidance of Professor Alicia Kowaltowski. The research was published in the American Journal of Physiology-Cell Physiology and revealed that exposure to cold and adrenergic stimulation modulate MitoKATP channel levels in brown adipose tissue.
To understand the channel's function better, the researchers removed the gene encoding an essential subunit of MitoKATP in human preadipocytes, precursor cells of adipose tissue. They observed a decrease in oxygen consumption, reduced cell proliferation, and difficulty in differentiating these precursors into mature adipocytes. In mouse cell lines, the absence of the same protein compromised cellular respiration in the precursor stage but not in already differentiated cells.
The most intriguing data came from mature adipocytes. When the researchers inhibited the MitoKATP channel, they observed an increase in oxygen consumption, suggesting that closing the channel is necessary for brown adipose tissue thermogenesis to reach its maximum efficiency. This observation was further confirmed in mitochondria isolated from mice treated with a compound that activates specific adrenergic receptors in brown fat, where inhibiting MitoKATP also increased oxygen consumption linked to thermogenesis.
Professor Kowaltowski highlights the study's findings, stating, "The results provide two pieces of complementary evidence for the importance of closing the MitoKATP channel in activating thermogenesis. Not only do cells with the channel closed generate more heat, but animals in a condition that stimulates heat production also have more closed channels. This indicates a signaling mechanism within the cell that leads to an ideal situation for heat generation."
The study's implications are significant, as they demonstrate the importance of closing the MitoKATP channel for maximum heat generation. Further research in this area could lead to new therapeutic strategies for obesity, focusing on regulating energy expenditure and promoting metabolic health.
