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Published on: June 25, 2017
Oleoylethanolamide attenuates early skeletal muscle metabolic remodeling induced by short-term high-fat diet exposure
Marzia Friuli1, Barbara Eramo2, Nisha Zahid2
1Department of Life Science, Health, and Health Professions, Link Campus University, Via del Casale di S. Pio V, Rome 00165, Italy.
Abstract:
Obesity develops through progressive metabolic alterations that arise long before overt disease, highlighting the need for pharmacological strategies capable of targeting the earliest tissue adaptations to dietary fat overload. Skeletal muscle plays a central role in systemic metabolic homeostasis and is among the first organs affected by high-fat diet (HFD) exposure. Oleoylethanolamide (OEA), a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, exerts broad metabolic actions in obesity, yet its impact on early skeletal muscle remodeling remains unknown. We investigated whether OEA could intercept the initial metabolic adaptations induced by HFD exposure in young rats. Male rats were exposed to HFD for seven weeks and treated with OEA (10 mg/kg, i.p.) during the final two weeks. Short-term HFD induced a coordinated remodeling of skeletal muscle characterized by lipid accumulation, suppression of the PPAR-α/CPT-1 axis, altered mitochondrial and redox homeostasis, extracellular matrix remodeling, impaired myogenic signaling, and a shift toward a glycolytic contractile program despite only modest body-weight gain. OEA largely attenuated such alterations, preserving skeletal muscle metabolic and structural homeostasis through coordinated improvement of lipid oxidative metabolism, mitochondrial energetic status, and tissue remodeling. These findings identify skeletal muscle as an early target of fat-induced metabolic dysfunction and support further investigation of OEA as a promising pharmacological strategy to intercept obesity-associated metabolic deterioration before overt obesity develops.
Insights
Oleoylethanolamide (OEA) prevents early skeletal muscle changes caused by high-fat diets. This research shows OEA preserves muscle metabolic and structural health, offering a potential strategy against obesity development.
Area of Science:
- Metabolic research
- Obesity research
- Skeletal muscle physiology
Background:
- Obesity stems from early metabolic changes preceding overt disease.
- Skeletal muscle is a key metabolic organ affected early by high-fat diets (HFD).
- Oleoylethanolamide (OEA), a PPAR-α agonist, has known metabolic benefits but its effect on early HFD-induced muscle changes is unclear.
Purpose of the Study:
- To investigate if OEA can counteract early metabolic adaptations in skeletal muscle due to HFD exposure.
- To understand OEA's impact on skeletal muscle remodeling during the initial stages of HFD-induced metabolic dysfunction.
Main Methods:
- Young male rats were fed an HFD for seven weeks.
- OEA (10 mg/kg) was administered intraperitoneally during the final two weeks of HFD exposure.
- Skeletal muscle adaptations were analyzed, focusing on lipid metabolism, mitochondrial function, redox balance, extracellular matrix, and myogenic signaling.
Main Results:
- Short-term HFD induced skeletal muscle lipid accumulation, suppressed the PPAR-α/CPT-1 pathway, and altered mitochondrial/redox homeostasis.
- HFD also caused extracellular matrix remodeling, impaired myogenic signaling, and shifted muscle towards glycolysis despite minimal weight gain.
- OEA treatment largely prevented these HFD-induced alterations, improving lipid oxidation, mitochondrial function, and tissue remodeling.
Conclusions:
- Skeletal muscle undergoes significant remodeling early in response to HFD, preceding substantial weight gain.
- OEA effectively preserves skeletal muscle metabolic and structural integrity against early HFD-induced changes.
- OEA shows promise as a pharmacological agent to target early metabolic dysfunction and prevent obesity development.