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      Triglycerides Mediate the Influence of Body Mass Index on Non-Alcoholic Fatty Liver Disease in a Non-Obese Chinese Population with Normal Low-Density Lipoprotein Cholesterol Levels

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          Abstract

          Introduction

          Over 25% of the world’s population has non-obese or lean non-alcoholic fatty liver disease (NAFLD), and the prevalence is higher than average in Asia. The present study focused on the relationship between body mass index (BMI) and non-obese NAFLD in non-overweight people in China, particularly the influence of triglycerides (TG) in the pathogenesis of non-obese NAFLD. The findings suggest new treatments for NAFLD patients with normal BMI, as well as provide an early warning system for the understanding and prevention of NAFLD in non-obese patients.

          Methods

          This cross-sectional study enrolled 159,959 Chinese subjects with BMI <24 kg/m 2 and normal levels of low-density lipoprotein cholesterol (LDL-c). The average age was 40.21 ± 13.88 years, and males accounted for 45.7%. A total of 15,907 (9.94%) patients with NAFLD were diagnosed by ultrasonography. Biochemical indicators were measured using an automated analyzer (Abbott AxSYM). The BMI (kg/m 2) was calculated from the weight (kg)/height in square meters (m 2). The BMI quartile was used as the column-stratified variable to determine the baseline distribution, and logistic regression analysis was used to assess the relationship between NAFLD and its risk factors, with multiple logistic regression used to assess the relationships between BMI or TG and NAFLD and multivariate linear regression used to analyze the association between BMI and TG, while mediation analysis was used to assess the mediation effect of TG.

          Results

          After adjustment of all covariates, the odds ratios were 1.788 (95% CI: 1.749–1.829; p < 0.00001) and 1.491 (95% CI: 1.451–1.532; p < 0.00001) for the association between BMI and TG with NAFLD incidence. The multivariate linear regression coefficient of BMI and TG was β = 0.027 (95% CI: 0.023–0.030; p < 0.00001). Mediation analysis showed that BMI contributed to 10.81% of lean NAFLD with a mediation effect of 2.98%.

          Conclusion

          In a Chinese population with BMI <24 kg/m 2 and normal LDL-c levels, BMI and TG were found to be independent predictors of NAFLD. The direct effect of BMI on non-obese NAFLD was 10.41%. The TG level was found to partially mediate the association.

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          Most cited references42

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          Mechanisms of NAFLD development and therapeutic strategies

          Mary Rinella, Arun Sanyal, Scott Friedman … (2018)
          There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression.
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            NAFLD: a multisystem disease.

            Christopher Byrne, Giovanni Targher (2015)
            Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords "non-alcoholic fatty liver disease" or "fatty liver" combined with "diabetes", "cardiovascular (or cardiac) disease", "cardiovascular mortality" or "chronic kidney disease" between 1990 and 2014. Articles published in languages other than English were excluded.
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              New trends on obesity and NAFLD in Asia

              Jian-Gao Fan, Vincent Wai-Sun Wong, Seung-Up Kim (2017)
              Traditionally, obesity and its related diseases have been considered a problem in Western countries. However, in the past two decades, urbanisation in many Asian countries has led to a sedentary lifestyle and overnutrition, setting the stage for the epidemic of obesity. This article reviews the epidemiological trend of obesity in Asia, with special emphasis on the emerging condition of non-alcoholic fatty liver disease (NAFLD). Currently, the population prevalence of NAFLD in Asia is around 25%, like many Western countries. While hepatocellular carcinoma and end-stage liver disease secondary to NAFLD remain uncommon, a rising trend has emerged. Around 8-19% of Asians with body mass indexes less than 25kg/m2 are also found to have NAFLD, a condition often described as "lean" or "non-obese" NAFLD. Although this condition is generally less severe than that in more obese patients, steatohepatitis and fibrotic disease are well recognized. Central adiposity, insulin resistance and weight gain are major risk factors, and genetic predisposition, such as the PNPLA3 polymorphism appears to be more important in the development of NAFLD in the non-obese population. Lifestyle modification remains the cornerstone of management for obesity and NAFLD, but few patients can achieve adequate weight reduction and even fewer can maintain the weight in the long run. While pharmacological agents have entered phase III development for steatohepatitis, Asian patients are under-represented in most drug trials. Future studies should define the optimal management of obesity and NAFLD in Asia.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Obes Facts
                Journal ID (iso-abbrev): Obes Facts
                Journal ID (hwp): OFA
                Journal ID (publisher-id): OFA
                Title: Obesity Facts
                Publisher: S. Karger AG (Basel, Switzerland )
                ISSN (Print): 1662-4025
                ISSN (Electronic): 1662-4033
                Publication date (Electronic): 24 January 2024
                Publication date Collection: April 2024
                Volume: 17
                Issue: 2
                Pages: 191-200
                Affiliations
                [a ]Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
                [b ]College of Integrated Traditional Chinese and Westem Medicine, Jining Medical University, Jining, China
                [c ]Health Care Centre, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
                Author notes
                Correspondence to: Chao Wei, qw26010539@ 123456163.com
                Article
                Publisher ID: 536447
                DOI: 10.1159/000536447
                PMC ID: 10987190
                PubMed ID: 38266508
                SO-VID: f0d88875-8076-47a2-bdf8-bb3273c4c7be
                Copyright © © 2024 The Author(s). Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                Date received : 5 July 2023
                Date accepted : 18 January 2024
                Date: 2024
                Page count
                Figures: 2, Tables: 5, References: 37, Pages: 10
                Funding
                This paper was supported by the Shandong Provincial Innovation Training Project (No. S202010443017), Shandong Medical and Health Science and Technology Development Plan Project (No. 202003101104), and 2019 Teachers’ Scientific Research Support Fund of Jining Medical University (No. JYFC2019KJ020).
                Categories
                Subject: Research Article

                Keywords: non-obese non-alcoholic fatty liver disease,body mass index,triglycerides,insulin resistance,redox imbalance
                Data availability:
                Keywords: non-obese non-alcoholic fatty liver disease, body mass index, triglycerides, insulin resistance, redox imbalance

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