US scientists have reported evidence explaining how obesity affects the body on a metabolic level by disrupting mitochondrial function – potentially paving the way for new obesity treatments and prevention strategies.
The researchers from the University of California-San Diego, whose study was published in Nature Metabolism, were led by Professor Alan Saltiel; his laboratory has been working for 40 years to understand how hormones like insulin control where and when energy is stored or used.
He told medicalnewstoday.com: ‘Obesity has a major impact on how well these hormones do their job. In the last few years, we’ve turned our attention to the ways fat and liver cells adapt to conditions associated with overeating when the cells are flooded with nutrients.
‘The interesting thing is these cells become more efficient at storing energy and less efficient at burning it, which is one reason why it is so hard to lose weight. We’ve been exploring the underlying molecular changes that explain this.’
He said obesity causes metabolic abnormalities in the body because it has to manage excessive amounts of energy due to the condition; the body has to find ‘a way to store energy or excess calories since there is a limit on how much can be burned off.
‘Thus adjustments are made, and this change in mitochondrial structure and function is one we highlight in this paper.’
Using a mouse model, Professor Saltiel’s team found when mice were fed a high fat diet, the mitochondria – the ‘powerhouse of the cell’ – within fat cells fragmented into smaller mitochondria, and these smaller mitochondria could not burn as much fat as when the larger mitochondria were all together.
Professor Saltiel explained: ‘In a normal, non-obese state, mitochondria maintain their health through a cycle of continual fusion and fission: they break apart and reform. We found changes that occur in obesity tip the scales so mitochondria break apart more – the process known as fission.’
During their research, the team also discovered the fragmentation of mitochondria was caused by a single molecule called RalA. Professor Saltiel commented: ‘We were surprised to discover RalA is a master regulator of mitochondrial fission, and when it is chronically activated in obesity, it tips the scales towards fission.’
Importantly, when scientists deleted the gene associated with the RaIA molecule in mice, they were able to protect them from weight gain from a high-fat diet. Researchers believe this finding could potentially lead to new ways of preventing and/ or treating obesity.
