Plasma sphingosine-1-phosphate is elevated in obesity.

Area of Science:

• Metabolic research
• Lipid metabolism
• Obesity research

Background:

• Dysfunctional lipid metabolism is central to obesity and insulin resistance, increasing cardiovascular risks.
• Obesity is associated with elevated ceramides, but the role of sphingosine-1-phosphate (S1P) remains unclear.
• Sphingosine-1-phosphate (S1P) is a critical signaling molecule with largely unknown concentrations in obesity.

Purpose of the Study:

• To investigate the impact of obesity on circulating sphingosine-1-phosphate (S1P) levels.
• To determine the relationship between S1P concentrations and markers of glucose metabolism and insulin sensitivity in obesity.

Main Methods:

• Measured plasma S1P levels in high-fat diet-induced obese mice, genetically obese (ob/ob) mice, and obese humans.
• Compared S1P levels between obese subjects and lean healthy controls.
• Analyzed correlations between plasma S1P and various metabolic parameters in humans.

Main Results:

• Circulating S1P levels were significantly elevated in both obese mouse models and obese humans compared to lean controls.
• In humans, plasma S1P positively correlated with body fat percentage, BMI, waist circumference, fasting insulin, HOMA-IR, HbA1c, total cholesterol, and LDL cholesterol.
• Fasting was observed to increase plasma S1P levels in lean healthy mice.

Conclusions:

• Elevated plasma S1P is a characteristic finding in both human and rodent obesity.
• Increased S1P concentrations are associated with key metabolic abnormalities, including adiposity and insulin resistance.