Lipoprotein Profiles in Class III Obese Caucasian and African American Women with Nonalcoholic Fatty Liver Disease

Abstract

Triglyceride content in the liver is regulated by the uptake, production and elimination of lipoproteins, and derangements in these processes contribute to nonalcoholic fatty liver disease (NAFLD). Previous studies show a direct relationship between intrahepatic fat and production of apolipoprotein B100 (apoB100) containing particles, VLDL and LDL, but little consensus exists regarding changes in lipoprotein production in the development of simple steatosis (SS) versus nonalcoholic steatohepatitis (NASH). Further, ethnic variations in lipoproteins among SS and NASH are unknown as is how such variations might contribute to the differential prevalence of disease among Caucasians versus African Americans. In this study, we assessed plasma lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy in 70 non-diabetic class III obese females recruited from the surgical weight loss clinic. Of these, 51 females were stratified by biopsy-staged NAFLD severity (histologically normal, SS, or NASH). NASH females displayed increased circulating triglycerides and increased VLDL particle number and size relative to those with histologically normal livers, while total and large LDL concentration decreased in SS versus NASH and correlated with increased insulin resistance (via HOMA2-IR). When Caucasian women were examined alone (n = 41), VLDL and triglycerides increased between normal and SS, while total LDL and apoB100 decreased between SS and NASH along with increased insulin resistance. Compared to Caucasians with SS, African American women with SS displayed reduced triglycerides, VLDL, and small LDL and a more favorable small to large HDL ratio despite having increased BMI and HOMA2-IR. These findings suggest that ApoB100 and lipoprotein subclass particle number and size can delineate steatosis from NASH in obese Caucasian females, but should be interpreted with caution in other ethnicities as African Americans with SS display relatively improved lipoprotein profiles. This may reflect variation in the relationship between dyslipidemia and NAFLD progression across gender and ethnicity.

Trial registration: ClinicalTrials.gov NCT00790309 NCT00802204 NCT00884494 NCT00983463.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Schematic illustrating lipoproteins particles under investigation in this study.

Fig 2. Ethnic Lipoparticle Comparisons.

African American women with simple steatosis had less atherogenic lipoprotein profiles relative than Caucasian women with simple steatosis. A) African Americans with simple steatosis (SS) were heavier (*P<0.05) and more insulin resistant B) as measured by homeostatic model assessment index 2 (HOMA2-IR, *P<0.05), yet displayed lower triglycerides (***P<0.001, not shown) and C) lower alanine aminotransferase (ALT, *P<0.05) than Caucasian SS. D) African Americans with SS displayed lower total very-low-density lipoprotein (VLDL) and VLDL sub-fractions (**P<0.01 for all, except small VLDL particle concentration, *P<0.05), E) decreased total and small low-density lipoprotein (LDL; *P<0.05 and **P<0.01, respectively), and F) improved high-density lipoprotein (HDL) profiles (increased large HDL, p = 0.002, and lower small LDL, P = 0.04) relative to Caucasian SS (E-F). Values are mean ± SEM. Data were analyzed by one-way ANOVA, followed by Mann-Whitney t Tests.