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.
Highlights
Hepatic steatosis stems from an imbalance between lipid supply and demand where excess fatty acids are stored in the liver as fat [1]
Lipoprotein profiles consisting of very-low density lipoproteins (VLDL), IDL, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) concentration and particle size (Fig 1) from 70 class III obese females undergoing bariatric surgery and 9 lean female subjects were measured by H-nuclear magnetic resonance (NMR) spectroscopy
We found that circulating VLDL particle number, VLDL size, and TG content were increased in SS relative to weight-matched obese normal females, whereas nonalcoholic steatohepatitis (NASH) females trended toward decreased VLDL with significant declines in LDL particle number and apolipoprotein B100 (apoB100) concentrations compared to SS
Summary
Hepatic steatosis stems from an imbalance between lipid supply and demand where excess fatty acids are stored in the liver as fat [1]. Hepatic triglyceride (TG) is eliminated from the liver via lipid oxidation or the secretion of TG-rich very-low density lipoproteins (VLDL) depending on local or peripheral energy needs [3, 4] This lipid and lipoprotein balance can become perturbed in the setting of obesity and type 2 diabetes (T2D), and may contribute to the development of nonalcoholic fatty liver disease (NAFLD) [5]. African Americans exhibit lower levels of TG and higher levels of HDL for a given BMI and degree of insulin resistance [11] It is unclear how lipoproteins vary in SS versus NASH of any ethnicity, with some studies reporting increased production of VLDL and LDL in NASH relative to SS while others report a decline [12,13,14,15,16,17]
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