Researchers in Japan have discovered that pterostilbene, a natural compound found in blueberries and grapes, can trigger muscle cells to break down excess fat. Published on September 1, 2026, in Volume 83 of the Food Bioscience journal, the study reveals how the polyphenol stabilizes a key protein regulating fat metabolism, offering a new direction for targeting metabolic health issues.
Targeting Ectopic Fat Inside Muscle Cells
Excess fat stored inside skeletal muscle has emerged as a significant 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, or subcutaneous fat, 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.
These deposits of ectopic fat—meaning fat located in abnormal places like the liver, heart, pancreas, and skeletal muscle—raise the risk of conditions such as type two diabetes and high blood pressure. Ectopic fat is more common in people who are obese or severely obese and can also build up in people with flat stomachs. While doctors normally recommend exercise to reduce these deposits, scientists are now investigating whether a compound could also help.
Screening Food Compounds at Shinshu University
A research team in Japan led by Associate Professor Takakazu Mitani of Shinshu University set out to find natural interventions for myosteatosis, a condition currently lacking approved treatments.
“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.”
Dr. Takakazu Mitani, Shinshu University
To investigate potential natural treatments, the researchers tested a collection of food-derived phytochemicals using cultured C2C12 mouse skeletal muscle cells. They investigated the potential for pterostilbene and four other compounds to clear ectopic fat in muscle cells, or fat stored within the cells. The other compounds tested were stilbene, resveratrol (found in grapes, cranberries, and others), 3-methoxy-resveratrol, and 4′-methoxy-resveratrol. Researchers exposed muscle cells that had ectopic fat deposits to all five compounds for seven days. Among the compounds tested, pterostilbene produced the strongest reduction in intracellular lipid accumulation, causing them to lose the most fat. Importantly, the treated muscle cells continued to grow and differentiate normally.
How Pterostilbene Stabilizes Metabolic Signaling
Further experiments showed that pterostilbene did not work by preventing fat from entering the cells. Instead, the team found that the compound stopped the breakdown of a protein called peroxisome proliferator-activated receptor delta (PPARδ), which is essential for fat breakdown. By doing this, it led to more of the protein accumulating inside the cell.
When PPARδ signaling is active, it promotes fatty acid oxidation and helps limit the accumulation of lipids inside cells. While previous research has linked the compound to beneficial metabolic effects in the liver and adipose tissue, scientists knew much less about how it might affect skeletal muscle.
Translating Lab Findings to Human Health
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. However, health experts note that the work remains based on laboratory tests and cell cultures.
‘Our findings establish a scientific framework for developing functional foods and nutritional supplements that target muscle fat metabolism,’ Dr Takakazu Mitani, lead study author, said. ‘However, beyond the potential of pterostilbene itself, this work provides an experimental framework for identifying other natural compounds [for weight loss].’
While specific diet supplementation with natural chemical compounds like grape polyphenols has shown relevance in cell culture and animal studies, clinical studies aiming to restore skeletal muscle mass and function with nutritional supplementation are still very scarce. There is an urgent need for clinical studies to validate results observed in animal models.
