New compound helps mice gain muscle and lose fat

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Scientists are working on new treatments to combat muscle loss and prevent obesity in aging humans. Drazen_/Getty Images
  • Sarcopenic obesity is a condition that involves age-related muscle loss accompanied by obesity.
  • Sarcopenic obesity can decrease the quality of life and increase an individual’s risk of hospitalization and death. There is also a lack of treatments for this condition.
  • A new study in mice has shown that a drug called BAM15 can prevent the loss of skeletal muscle mass and function, and prevent weight gain.
  • The study suggests that BAM15 achieved this by reducing inflammation and improving the function of mitochondria, the powerhouses of the cells.

A recent study published in the Journal of Cachexia, Sarcopenia and Muscle shows that a drug called BAM15 can combat weight gain and muscle loss in sarcopenic obesity.

The study found that BAM15 was effective in combating deficits associated with sarcopenic obesity, including increased energy expenditure, reduced inflammation, and improved mitochondrial function in mice.

The study’s co-author Christopher Axelrod, a researcher at Pennington Biomedical Research Center, told Medical News Today:

“Sarcopenic obesity is a debilitating disease, and no targeted therapies are currently available. This treatment approach provides the first evidence that sarcopenic obesity can be treated by decreasing the efficiency of energy production.”

Axelrod said that the study’s findings could be significant in refining/developing effective and safe drugs in humans.

Sarcopenia is a condition characterized by the gradual loss of skeletal muscle mass and strength and is a part of the natural aging process. Obesity can worsen the effects of sarcopenia, resulting in a greater loss of muscle mass and function.

Sarcopenia coupled with obesity is known as sarcopenic obesity and is associated with worse health outcomes than sarcopenia and obesity alone. Specifically, sarcopenic obesity is associated with a much more rapid decline in physical function and an elevated risk of cardiovascular diseases, hospitalization, and death.

Sarcopenic obesity involves a decline in energy expenditure instead of excess intake of calories. Thus, treatments that could increase energy expenditure could help combat sarcopenic obesity.

Obesity and sarcopenia share common biological mechanisms, including the impaired functioning of mitochondria in skeletal muscle cells. Mitochondria are organelles in the cell that are responsible for energy production and are critical for muscle function.

Energy generation in the mitochondria consists of two distinct processes that are coupled together, and the coupling of these two processes determines the efficiency of energy production.

Studies have shown that the uncoupling of the two processes using drugs called mitochondrial uncoupling agents can result in the generation of heat instead of storing excess energy as fat.

The study’s authors had already shown that BAM15—a mitochondrial uncoupling agent—could prevent obesity in young mice maintained on a high fat diet. The present study aimed to assess the ability of BAM15 to counter the effects of sarcopenic obesity in aged mice.

To assess the impact of BAM15 on sarcopenic obesity, the researchers used aged mice that were maintained on a high fat diet and treated with BAM15 for 10 weeks. The control group consisted of animals maintained on a high fat diet without BAM15 and showed an increase in body weight over the study period.

Although animals in both the control and BAM15 group did not have different food intakes, the animals treated with BAM15 did not show an increase in body weight, unlike the control group. The BAM15-treated mice showed lower body fat levels than the control animals, which was likely responsible for the absence of weight gain.

BAM15-treated mice also had more muscle mass and greater muscle strength than control animals. This suggested that mitochondrial uncoupling preserved muscle mass and function.

Moreover, BAM15 treatment resulted in higher physical activity and energy expenditure levels.

The researchers then assessed the impact of BAM15 on the biological processes underlying sarcopenic obesity.

Chronic low-grade inflammation is a feature of both obesity and aging and contributes to muscle function and mass loss.

The researchers found that BAM15 treatment lowered markers of local inflammation in the skeletal muscle as well as systemic inflammation.

Similarly, a decline in mitochondrial function and a decrease in the number of healthy mitochondria are hallmarks of age-related muscle loss. The researchers found that BAM15 improved mitochondrial function, enhanced the generation of new mitochondria, and facilitated the removal of damaged mitochondria.

Muscle wasting in age-related sarcopenia is also associated with increased protein degradation and the accumulation of misfolded proteins.

Proteins are composed of one or more chains of amino acids that are folded in a specific shape. Misfolded proteins tend to aggregate together, leading to cellular stress, and subsequently, cell death. The accumulation of misfolded proteins is observed in skeletal muscles during aging and obesity, leading to muscle degradation.

The researchers found that BAM15 treatment in aged mice reduced the expression of markers associated with protein misfolding and degradation, cellular stress, and cell death in skeletal muscle tissue.

The study’s co-author Dr. John Kirwan, executive director of Pennington Biomedical Research Center, told MNT:

“The study provides the first evidence that BAM15, a mitochondrial uncoupler, prevents sarcopenic obesity, or age-related muscle loss accompanied by an increase in fat tissue. The research was conducted in older mice (equivalent to age 65 in humans).”

Dr. Kirwan said that more research will be needed to determine whether the treatment will be effective in humans.

“[T]he findings have important implications for improving the quality of life for older adults, especially for the rapidly growing number of people with obesity. Preventing, delaying, or reversing the causes and consequences of sarcopenic obesity may allow people to live longer and healthier lives.”
⁠— Dr. John Kirwan, study co-author

https://www.medicalnewstoday.com/articles/could-an-experimental-drug-help-prevent-aging-and-treat-obesity

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