Objective: Dysregulation of cholesterol and sphingolipids (SPL) is associated with metabolic diseases. This study tested the correlation between plasma sphingolipids and plasma cholesterols (Chl), triglycerides (TG), and adiposity factors in normoglycemic individuals.

Methods: We assayed plasma levels of 58 species of SPL, including ceramides (Cer), monohexosylceramides (MHC), sphingomyelins (SM), from 240 normoglycemic Black and White participants. SPL profiles were analyzed by LC-MS/MS and correlated with plasma profiles of high-density Chl (HDL), low-density Chl (LDL), TG, and total Chl, along with participants’ biometric indicators of adiposity (BMI, waist circumference, total fat mass, total lean mass, and trunk fat mass).

Results: The subjects’ mean age was 43.08 ± 12.02 y from 150 females and 90 males, 129 Black and 111 White, with BMI 29.44 ± 6.23 kg/m2, fasting glucose 91.35 ± 6.91 mg/dl and 2-hr plasma glucose 122.77 ± 26.32. We found the total plasma Cer, MHC, and SM correlated positively with total Chl (r=0.3, p<0.001; r=0.23, p<0.01; and r=0.22, p<0.01) and LDL (r=0.3, p<0.01; r=0.22, p<0.01; and r=0.21, p<0.05). Strong positive correlations were observed with MHC C26:1 and total Chl (r=0.34, p<0.0001) and LDL (r=0.36, p<0.0001), and total and very-long-chain (VLC) SM species with HDL (r=0.2, p<0.05 and r=0.38, p<0.0001). Strong negative correlations were observed with MHC C32:0 and SM C26:0/C26:1 ratio with HDL (r= -0.3, p<0.001 and r= - 0.36, p<0.0001), and in SM C16:0/C18:0 ratio with LDL (r= -0.3, p<0.001). VLC-SM species and SM C16:0/C18:0 ratio correlated negatively with BMI (r=-0.2, p<0.01; r= -0.25, p<0.000), waist circumference (r= -0.2, p<0.01; r= -0.2, P<0,01), and trunk fat mass (r= -0.2, p<0.05; r= -0.2, p<0.05).

Conclusions: This study demonstrates novel associations between adiposity and circulating levels of certain SPL and lipoproteins. Thus, plasma SPL may provide additional insights, beyond routine lipid profile, on metabolic pathophysiology.

Disclosure

N. Mandal: None. R. Grambergs: None. N. Feto: None. J.Y. Wan: None. F.B. Stentz: None. S. Dagogo-Jack: Consultant; Merck Sharp & Dohme Corp., Medtronic, Bayer Inc. Stock/Shareholder; Aerami.

Funding

National Institute of Health (R01 DK128129)

© 2024 by the American Diabetes Association
2024
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