Among the many ways obesity negatively impacts the human body is through an impaired metabolism and reduced endurance in skeletal muscle, and a new study has now shed light on a molecular process underpinning the condition. With this new understanding comes new opportunities to combat obesity, with the authors also demonstrating how a growth factor found in a South American plant can alleviate its deleterious effects.
The study carried out at the University of Hong Kong sought to dig into the reasons why fat metabolism works at a slower rate in obese patients. Scientists suspect this is the result of abnormally functioning mitochondria, the cell's powerhouses that turn nutrients into energy, but how obesity induces these effects remains unclear.
In search of answers to this question, the researchers turned to mouse models engineered specifically for the study of obesity's effects on skeletal muscle. This involved deleting the gene for a protein called brain-derived neurotrophic factor (BDNF). This is known to play a key role in the maintenance of neurons, but recent studies have suggested that it is also a hormone produced by skeletal muscle tissue, also known as a myokine.
Through these experiments, the scientists found that obesity did reduce the amount of BDNF in the skeletal muscle tissue of the mice. They also found that mice without BDNF in their muscle tissue more readily gained body weight and developed insulin resistance when fed a high-fat diet. They also exhibited lower energy expenditure. Zeroing in on the reasons why, the scientists found that the mitochondria in the mice lacking BDNF were unable to recycle materials as normal. This meant that damaged mitochondria built up in the tissues of the obese mice, interfering with their metabolism of lipids and sensitivity to insulin.
The scientists then built on these findings through further experiments on cultured muscle cells deficient in BDNF, which enabled them to pinpoint a signaling pathway behind the malfunctioning mitochondria. They then turned to a naturally occurring flavone in the South American plant Godmania aesculifolia called 7,8-dihydroxyflavone that mimics BDNF and is currently being investigated in clinical trials for Alzheimer's disease, and found that this alleviated the mice's mitochondrial dysfunction.
Earlier research has also shown that 7,8-dihydroxyflavone can be an effective agent in reducing body weight and improving insulin sensitivity in overweight mice, so these latest findings add further weight to the idea that it could be an effective tool to tackle obesity in humans.
"Clearly, muscle-derived BDNF is a weight-control protein by increasing the energy expenditure and maintaining insulin sensitivity," says study author Dr Chi Bun Chan. "BDNF has long been considered a brain-localized peptide, and its importance in peripheral tissues has been underestimated. Our study provides a new insight to this area, and hopefully we can unlock more functions of this myokine using our MBKO (Muscle-specific BDNF Knockout) mice."
The research was published in the journal Autophagy.
Source: University of Hong Kong