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Presence of sarcopenia identifies a special group of lean NAFLD in middle-aged and older people

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Abstract

Background

Sarcopenia, the age-related loss of muscle mass and function, is closely associated and frequently concomitant with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the clinical features of the sarcopenic NAFLD patients from middle-aged and older people.

Methods

A total of 1305 patients with NAFLD from the Shanghai Changfeng Study were included for analysis. Sarcopenia was diagnosed based on the height-adjusted appendicular skeletal muscle mass (ASM/height2). We comprehensively analyzed the metabolic phenotype, carotid artery condition, liver fibrosis score, and serum metabolomic profile of each participant.

Results

Among the middle-aged and older population, 68.1% of patients with sarcopenia and NAFLD were lean. Sarcopenia was independently associated with increased risk of carotid plaque (OR, 2.22; 95%CI 1.23–4.02) and liver fibrosis (OR, 2.07; 95%CI 1.24–3.44), and the sarcopenic lean NAFLD patients were characterized by a higher risk of carotid plaque (p = 0.008) and liver fibrosis (p = 0.001) than the non-sarcopenic lean NAFLD patients, despite their lower BMI and similar prevalence of metabolic syndrome and diabetes. Further serum metabolomic examination indicated that the sarcopenic lean NAFLD patients presented a distinct metabolomic profile prone to carotid plaque and liver fibrosis, with upregulated serum valine, N-acetylneuraminyl-glycoproteins, lactic acid, small LDL triglycerides and VLDL5 components, and reduced components of HDL4. A sarcopenic characterization score based on above metabolites was established and could also predict increased risk of carotid plaque and liver fibrosis.

Conclusion

The presence of sarcopenia identifies a special subgroup of lean NAFLD with increased risk of cardiovascular disease and liver fibrosis clinically.

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Abbreviations

ALT:

Alanine transaminase

ApoA1:

Apolipoprotein A1

ApoA2:

Apolipoprotein A2

ApoB:

Apolipoprotein B100

ASM/height2 :

Height-adjusted appendicular skeletal muscle mass

AST:

Aspartate transaminase

AWGS:

Asian working group for sarcopenia

BMI:

Body mass index

CE:

Cholesterol esters

DBP:

Diastolic blood pressure

DXA:

Dual-energy X-ray absorptiometry

FC:

Free cholesterol

FDR:

False discovery rate

FIB-4:

Fibrosis 4 score

FPG:

Fasting plasma glucose

HDL:

High-density lipoprotein

HOMA-IR:

Homeostasis model assessment for insulin resistance

hs-CRP:

High-sensitivity C-reactive protein

HR:

Hazard ratio

ICD-10:

The 10th revision of international classification of diseases

IDL:

Intermediate density lipoprotein

LDL:

Low-density lipoprotein

LFC:

Liver fat content

NAFLD:

Non-alcoholic fatty liver disease

NAG:

N-acetyl-glycoproteins

NAG1:

N-acetylglucosamine/galactosamine-glycoproteins

NAG2:

N-acetylneuraminyl-glycoproteins

NASH:

Non-alcoholic steatohepatitis

NHANES III.:

Third National Health and Nutrition Examination Survey

OGTT:

Oral glucose tolerance test

OR:

Odds ratio

PPG:

Post-load plasma glucose

PL:

Phospholipids

SBP:

Systolic blood pressure

TC:

Total cholesterol

TG:

Triglycerides

VLDL:

Very low-density lipoprotein

1H-NMR:

1-H nuclear magnetic resonance spectroscopy

95%CI:

95% Confidence interval

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Funding

We have obtained financial supports from the Ministry of Science and Technology of China (2018YFE0201603, 2020YFE0201600), the Shanghai Pujiang Talent Project (20PJ1402300), the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Science and Technology Commission of Shanghai Municipality (16JC1400500, 16411954800), the National Natural Science Foundation of China (81873660, 31821002 and 82100849), and Foundations from Zhongshan Hospital, Fudan University (2020ZSLC58, 2021ZSQN07).

Author information

Author notes

  1. Xiaopeng Zhu, Qingxia Huang and Shuai Ma have contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China

    Xiaopeng Zhu, Shuai Ma, Qi Wu, Li Wu, Xiaoming Li, Qian Li, Qiqige Aleteng, Huandong Lin, Xin Gao & Mingfeng Xia

  2. State Key Laboratory of Genetic Engineering, School of Life Sciences, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Human Phenome Institute, Zhongshan Hospital, Fudan University, 825 Zhangheng Rd, Shanghai, 200438, China

    Qingxia Huang & Huiru Tang

  3. Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China

    Lingyan Chen, Hui Ma & Yu Hu

  4. Department of Ultrasonography, Zhongshan Hospital, Fudan University, Shanghai, China

    Wanyuan He

  5. Department of Nutrition, Center of Clinical Epidemiology and EBM, Zhongshan Hospital, Fudan University, Shanghai, China

    Jian Gao

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  1. Xiaopeng Zhu
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Contributions

Study concept and design: MX, XG, HT. Acquisition of data: XZ, QH, SM, LC, QW, LW, XL, HM, QL, QA, MX, HL. Analysis of data: XZ, SM, QH, JG, MX. Technic support and data interpretation: QH, WH. Data management: HL. Manuscript drafting: XZ, MX. Manuscript revision: MX, XG, HT, YH. Obtained funding; XG, HT, MX, XZ. MX and XG are the guarantors of this work and, as such, takes responsibility for the integrity of the work as a whole, from inception to published article.

Corresponding authors

Correspondence to Huiru Tang, Xin Gao or Mingfeng Xia.

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Conflict of interests

Xiaopeng Zhu declares that there is no duality of interest. Qingxia Huang declares that there is no duality of interest. Shuai Ma declares that there is no duality of interest. Lingyan Chen declares that there is no duality of interest. Qi Wu declares that there is no duality of interest. Li Wu declares that there is no duality of interest. Hui Ma declares that there is no duality of interest. Xiaoming Li declares that there is no duality of interest. Qian Li declares that there is no duality of interest. Qiqige Aleteng declares that there is no duality of interest. Yu Hu declares that there is no duality of interest. Wanyuan He declares that there is no duality of interest. Jian Gao declares that there is no duality of interest. Huandong Lin declares that there is no duality of interest. Huiru Tang declares that there is no duality of interest. Xin Gao declares that there is no duality of interest. Mingfeng Xia declares that there is no duality of interest.

Ethical approval

The study was approved by the Research Ethics Committees of Zhongshan Hospital, Fudan University (No. 2008-119 and B2013-132).

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Each participant provided written informed consent.

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Zhu, X., Huang, Q., Ma, S. et al. Presence of sarcopenia identifies a special group of lean NAFLD in middle-aged and older people. Hepatol Int 17, 313–325 (2023). https://doi.org/10.1007/s12072-022-10439-z

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