Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents

Justin Chin; Trevor A Mori; Leon A Adams; Lawrence J Beilin; Rae-Chi Huang; John K Olynyk; Oyekoya T Ayonrinde

doi:10.1016/j.jhepr.2020.100150

Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents

JHEP Rep. 2020 Jul 24;2(6):100150. doi: 10.1016/j.jhepr.2020.100150. eCollection 2020 Dec.

Authors

Justin Chin¹, Trevor A Mori², Leon A Adams^{2

3}, Lawrence J Beilin², Rae-Chi Huang⁴, John K Olynyk^{1

5}, Oyekoya T Ayonrinde^{1

2

6}

Affiliations

¹ Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia.
² School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia.
³ Department of Hepatology and Liver Transplantation, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
⁴ Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.
⁵ School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
⁶ Faculty of Health Sciences, Curtin University, Bentley, WA, Australia.

Abstract

Background & aims: Remnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors.

Methods: Adolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed.

Results: NAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR.

Conclusions: There is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk.

Lay summary: Remnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease.

Keywords: AIx, Aortic Augmentation Index; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Adiposity; Arterial stiffness; C-AGPH-HR75, Central Augmentation Pressure/Pulse Height Ratio at Heart Rate 75; Cardiometabolic risk; GGT, gamma-glutamyl transpeptidase; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment of insulin resistance; IDF, International Diabetes Federation; LDL-C, low-density lipoprotein cholesterol; Lipids; Metabolic syndrome; NAFLD; NAFLD, non-alcoholic fatty liver disease; OR, odds ratio; Q1, lowest (first) quartile; Q2, second quartile; Q3, third quartile; Q4, top (fourth) quartile; RLP-C, remnant lipoprotein cholesterol; Raine study; T2DM, type 2 diabetes mellitus; TG, triglycerides; VLDL, very-low-density lipoprotein; hsCRP, high-sensitivity C-reactive protein.