Japanese researchers found that pterostilbene, a naturally occurring compound in blueberries and grapes, reduced fat accumulation in cultured mouse muscle cells by preserving a protein involved in fatty acid metabolism, although human studies are still needed.
By yourNEWS Media Newsroom.
A naturally occurring compound found in blueberries, grapes and other berries helped muscle cells break down accumulated fat in laboratory experiments, offering researchers a potential new avenue for studying metabolic disorders associated with abnormal fat storage in muscle.
Scientists at Shinshu University in Japan identified pterostilbene as the strongest performer among several food-derived compounds screened for their ability to reduce lipid accumulation in cultured mouse skeletal muscle cells.
The research, published Sept. 1 in Food Bioscience, found that pterostilbene did more than prevent additional fat from entering muscle cells. It appeared to promote the breakdown of fat already stored inside them while increasing activity associated with fatty acid oxidation.
Associate Professor Takakazu Mitani led the research team, which investigated naturally derived compounds as possible tools for addressing ectopic lipid accumulation — the abnormal storage of fat in tissues where large quantities are not normally intended to accumulate.
In skeletal muscle, excessive intracellular fat can interfere with the tissue’s ability to efficiently use glucose and fatty acids. Persistent accumulation has been associated with insulin resistance, obesity, age-related physical decline and prolonged inactivity.
Researchers created an experimental model of substantial fat accumulation using C2C12 mouse skeletal muscle cells. The cells were exposed to a lipogenic induction cocktail designed to produce pronounced intracellular lipid buildup, allowing scientists to compare the effects of different food-derived phytochemicals.
Pterostilbene produced the strongest reduction in stored lipids among the compounds examined.
Treated muscle cells released increased amounts of glycerol, a byproduct associated with the breakdown of stored triglycerides. Researchers also detected increased expression of genes involved in fatty acid oxidation, indicating that the cells were processing stored fat rather than merely preventing additional lipid accumulation.
The distinction could be important because some experimental strategies seek to reduce muscle fat by limiting fatty acid entry into cells. Pterostilbene instead appeared to stimulate metabolic processes capable of clearing lipids already present.
Researchers traced the effect to an unexpected mechanism involving a PPAR protein that regulates genes responsible for fatty acid metabolism in skeletal muscle.
Rather than directly switching on the receptor, pterostilbene appeared to preserve more of the protein inside the cell.
Normally, cellular proteins can be marked for destruction and broken down through the ubiquitin-proteasome system. Researchers found that pterostilbene interfered with degradation of the PPAR protein, allowing greater amounts of it to remain available and support expression of genes involved in burning fatty acids.
That mechanism distinguishes pterostilbene from synthetic compounds designed to activate PPAR receptors directly.
One such experimental agonist, GW501516, increases fatty acid oxidation by binding directly to a PPAR receptor. Prolonged exposure to the compound, however, has been associated with serious adverse effects, including carcinogenicity in preclinical research.
Pterostilbene did not operate through the same direct-binding mechanism, according to the study. Instead, researchers found that it increased the amount of the relevant PPAR protein by reducing its degradation.
Further analysis indicated that pterostilbene’s chemical structure is central to the effect.
The compound is a naturally occurring dimethoxy analog of resveratrol, another plant polyphenol that has been widely studied for possible metabolic effects. Researchers found that pterostilbene’s 3,5-dimethoxy structure was critical to its ability to influence lipid metabolism, helping explain why it behaved differently from resveratrol and related compounds.
Pterostilbene may also possess a pharmacological advantage over resveratrol because of how efficiently it is absorbed.
Its oral bioavailability has been estimated at approximately 80%, substantially higher than that of resveratrol. Greater bioavailability means a larger proportion of an ingested compound can potentially reach circulation and biologically relevant tissues.
The laboratory findings fit into a broader area of research examining metabolic flexibility in skeletal muscle.
Muscle tissue is a major consumer of energy and plays a central role in regulating whole-body metabolism. Healthy muscle can shift between carbohydrates and fats as energy sources depending on nutritional conditions and physical demands.
Excessive accumulation of fat inside muscle cells can interfere with that flexibility.
High-fat diets, inactivity and metabolic dysfunction can promote intramuscular lipid accumulation and impair mitochondrial activity, contributing to a cycle in which the tissue becomes progressively less efficient at handling glucose and fatty acids.
Abnormal fat accumulation within and around muscle, sometimes referred to as myosteatosis, has consequently attracted increasing attention in research involving metabolic disease, aging and physical function.
There currently are no approved medications specifically designed to eliminate this form of muscle fat, making nutritional and food-derived interventions an area of particular interest.
The Shinshu University researchers screened phytochemicals in part because naturally occurring dietary compounds may offer different safety characteristics from synthetic metabolic drugs.
Pterostilbene was the most effective compound tested, while genistein, a phytochemical commonly associated with legumes, and fisetin, found in strawberries and other fruits, also demonstrated notable lipid-reducing effects.
Pterostilbene occurs naturally in blueberries and grapes and can also be found in cranberries and other members of the Vaccinium family.
The findings do not mean, however, that eating blueberries has been demonstrated to remove accumulated fat from human muscle.
Researchers noted that pterostilbene is present in relatively small amounts in whole foods. The concentrations required to reproduce the cellular effects observed in the laboratory may therefore be difficult to obtain through ordinary dietary consumption alone.
Its relatively high bioavailability nevertheless makes the compound a potential candidate for future research involving functional foods, nutraceuticals or other targeted nutritional products.
Blueberries themselves contain numerous additional plant compounds, including anthocyanins and proanthocyanidins, that have previously been investigated for antioxidant and anti-inflammatory properties.
The new research isolates pterostilbene as one compound of interest and proposes a specific cellular mechanism through which it may influence muscle lipid metabolism.
Significant questions remain before those findings can be translated into recommendations for people.
The experiments were conducted in cultured mouse muscle cells rather than humans. Researchers will need to determine whether pterostilbene produces similar effects in living organisms, what concentrations are required, how selectively it acts on its intended targets and whether long-term use is safe.
Future studies will also need to establish whether preserving PPAR proteins in this manner produces meaningful improvements in insulin sensitivity, muscle function or other metabolic outcomes.
The research nevertheless provides scientists with a new framework for investigating food-derived compounds that influence fat metabolism without directly activating the receptors targeted by some synthetic drugs.
By demonstrating that a naturally occurring berry compound can stabilize a key metabolic protein and promote breakdown of accumulated lipids in muscle cells, the Shinshu University team has identified a potential pathway for further study as researchers search for new approaches to metabolic disease and age-related muscle dysfunction.
Source: Natural News
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