Excess fat stored inside skeletal muscle has become an important metabolic health concern. This type of fat buildup can be encouraged by high-fat diets, physical inactivity, and aging. Unlike fat stored under the skin, lipid droplets that accumulate within muscle cells can interfere with normal muscle function and make it harder for the body to efficiently use glucose and fatty acids. Over time, this reduced metabolic flexibility can contribute to insulin resistance. Finding ways to limit excess fat inside skeletal muscle could therefore be important for supporting healthy aging and reducing the risk of lifestyle-related disease.
One pathway that plays an important role in this process involves peroxisome proliferator-activated receptor δ (PPARδ). When PPARδ signaling is active, it promotes fatty acid oxidation and helps limit the accumulation of lipids inside cells. Researchers have become increasingly interested in food-derived bioactive compounds that may influence this pathway, but exactly how these substances affect PPARδ has remained unclear.
A Berry Compound Targets Muscle Fat Metabolism
A research team in Japan led by Associate Professor Takakazu Mitani of Shinshu University has now identified pterostilbene as a natural dietary compound that can stabilize PPARδ and influence fat metabolism inside muscle cells.
Pterostilbene is a naturally occurring polyphenol found in blueberries, grapes, and other berries. Previous research has linked the compound to beneficial metabolic effects in the liver and adipose tissue, but scientists knew much less about how it might affect skeletal muscle. The new findings were published in Volume 83 of the Food Bioscience journal on September 1, 2026.
“We currently lack approved treatments specifically targeting myosteatosis,” says Dr. Mitani. “This critical gap led our team to screen food-derived compounds for natural, dietary interventions. During the screening, we identified pterostilbene and focused our investigation on uncovering its precise mechanism of action.”
Screening Food Compounds for Fat Reduction
To investigate potential natural treatments, the researchers tested a collection of food-derived phytochemicals using cultured C2C12 mouse skeletal muscle cells. They examined whether the compounds could reduce abnormal fat accumulation inside the cells without interfering with normal muscle development.
Among the compounds tested, pterostilbene produced the strongest reduction in intracellular lipid accumulation. Importantly, the treated muscle cells continued to grow and differentiate normally.
Further experiments showed that pterostilbene did not work by preventing fatty acids from entering the muscle cells. Instead, the researchers detected increased release of glycerol outside the cells, which is an important sign that stored fat is being broken down.
The treated cells also showed greater expression of genes involved in fatty acid oxidation. Together, these results suggest that pterostilbene encourages muscle cells to break down stored lipids and process them for energy.
Protecting a Key Fat Metabolism Protein
The researchers then investigated the molecular mechanism behind these effects and found that pterostilbene significantly increased PPARδ signaling.
The way it accomplished this was unexpected. Many experimental compounds designed to stimulate PPARδ work by binding directly to the receptor and activating it. Pterostilbene appeared to operate differently.
Instead of directly activating PPARδ, the compound increased the amount of PPARδ protein present inside the cells. It did this by preventing the protein from being broken down through the ubiquitin-proteasome pathway.
By slowing the degradation of PPARδ, pterostilbene allowed more of the protein to remain available inside the cell. This stabilization increased PPARδ transcriptional activity and boosted the activity of genes involved in lipid metabolism.
“Our findings establish a scientific framework for developing functional foods and nutritional supplements that target muscle fat metabolism. However, beyond the potential of pterostilbene itself, this work provides an experimental framework for identifying other natural compounds that can stabilize the PPARδ protein,” mentioned Dr. Mitani.
Potential Implications for Metabolic Health
With metabolic diseases becoming increasingly common worldwide, the findings provide a starting point for studying dietary approaches that could eventually contribute to strategies for obesity, type 2 diabetes, and age-related metabolic decline.
However, the results are still limited to molecular experiments in cultured mouse muscle cells. They do not yet demonstrate that pterostilbene can prevent or treat these conditions in animals or humans.
Even so, the researchers say the compound could serve as a promising candidate bio-ingredient for the food and healthcare industries as they explore new functional products aimed at muscle fat metabolism.
Additional in vivo research will be necessary to determine whether the effects translate beyond cultured cells. Future studies will also need to evaluate effectiveness, safety, and how selectively pterostilbene acts on its intended biological targets before the findings can be developed into practical nutritional or pharmaceutical applications.
