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The association between visceral adipocyte hypertrophy and NAFLD in subjects with different degrees of adiposity

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Abstract

Objective

To investigate the association between visceral adipocyte hypertrophy and the onset and development of non-alcoholic fatty liver disease (NAFLD) in subjects with different degrees of adiposity.

Methods

Omental adipose tissue and liver biopsies were collected from obese subjects. NAFLD was defined according to the NASH Clinical Research Network scoring system. Adipocyte size was measured using pathological section analysis. Adipose tissue insulin resistance (Adipo-IR) was calculated as fasting insulin (pmol/L) × fasting free fatty acid concentration (mmol/L).

Results

In total, 275 obese patients were enrolled, including 158 females and 58 males with NAFLD. In females, adipocyte size was significantly larger in NAFLD participants as compared to the controls (99.37 ± 14.18 vs. 84.14 ± 12.65 \(\upmu\)m, p < 0.001). Moreover, adipocyte size was larger in females with non-alcoholic steatohepatitis (NASH) as compared to those with non-alcoholic fatty liver (NAFL) (101.45 ± 12.77 vs. 95.79 ± 15.80 \(\upmu\)m, p = 0.015). Mediation analysis showed that adipocyte size impacted the NAFLD activity score through Adipo-IR (b = 0.007 [95% bootstrap CI 0.002, 0.013]). Furthermore, the females were divided into: Q1 (BMI < 32.5 kg/m2), Q2 (BMI 32.5–35.5 kg/m2), Q3 (BMI 35.5–38.8 kg/m2) and Q4 (BMI ≥ 38.8 kg/m2) according to BMI quartiles. Omental adipocyte size was larger in NAFLD subjects in Q1–Q3, but not in Q4. No similar results were observed in males.

Conclusion

For the first time, we reported that visceral adipocyte hypertrophy was associated with the onset and progression of NAFLD in mild to moderate adiposity but not in severe obesity, which may be mediated by adipose tissue insulin resistance.

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Data availability

Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China Grant Awards (82030026, 82070837 and 81970704), the Six Talent Peaks Project of Jiangsu Province of China (YY-086) and Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2021-LCYJ-DBZ-10).

Author information

Author notes

  1. Haixiang Sun, Da Fang, Hongdong Wang, and Jin Wang have contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, Branch of National Clinical Research Centre for Metabolic Diseases, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China

    Haixiang Sun, Hongdong Wang, Jin Wang, Yue Yuan, Shanshan Huang, Huayang Ma, Tianwei Gu & Yan Bi

  2. Endocrine and Metabolic Disease Medical Center, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China

    Haixiang Sun, Da Fang, Hongdong Wang, Jin Wang, Yue Yuan, Shanshan Huang, Huayang Ma, Tianwei Gu & Yan Bi

  3. Department of Endocrinology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

    Da Fang, Tianwei Gu & Yan Bi

Authors
  1. Haixiang Sun
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Contributions

HXS and DF and HDW participated in data collection, performed the statistical analysis, and prepared the figures and tables, and wrote the manuscript. JW participated in the supplementary experiment, and wrote the revised manuscript. YY and SSH and HYM participated in data collection and the interpretation of data. TWG supervised the project, designed the study and co-wrote the manuscript. YB supervised the project, designed the study, interpreted the results, and revised the manuscript.

Corresponding authors

Correspondence to Tianwei Gu or Yan Bi.

Ethics declarations

Conflict of interest

Haixiang Sun, Da Fang, Hongdong Wang, Jin Wang, Yue Yuan, Shanshan Huang, Huayang Ma, Tianwei Gu, Yan Bi declare that they have no conflict of interest to disclose.

Animal research (ethics)

Not applicable.

Consent to participate (ethics)

The study conforms to the guidelines of the Declaration of Helsinki and was approved by Nanjing Drum Tower Hospital Committee (201703008). Written informed consent was obtained from each subject in the study.

Consent to publish (ethics)

All the authors contributed to the interpretation of the data and reviewed and approved the manuscript.

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Supplementary Information

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Supplementary file1 (DOCX 26 KB)

12072_2022_10409_MOESM2_ESM.tif

Supplementary figure 1. The human mature adipocytes were separated into two fractions (small adipocyte (≤ 90μm) and large adipocyte (> 90μm)) by 90 μm nylon mesh. (A) Large (n = 6) and small (n = 6) adipocytes were used to compared the expressions of proinflammatory cytokines; (B) Large (n = 6) and small (n = 6) adipocytes were used to compared the expressions of adipokines. The data are shown as the means ± SEM. * p <0.05, ** p <0.01 (statistical analysis was based on Student’s t test)

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Sun, H., Fang, D., Wang, H. et al. The association between visceral adipocyte hypertrophy and NAFLD in subjects with different degrees of adiposity. Hepatol Int 17, 215–224 (2023). https://doi.org/10.1007/s12072-022-10409-5

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  • DOI: https://doi.org/10.1007/s12072-022-10409-5

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