Sun Haixiang, Fang Da, Wang Hongdong, Wang Jin, Yuan Yue, Huang Shanshan, Ma Huayang, Gu Tianwei, Bi Yan
Department of Endocrinology, Branch of National Clinical Research Centre for Metabolic Diseases, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China.
Endocrine and Metabolic Disease Medical Center, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China.
Hepatol Int. 2023 Feb;17(1):215-224. doi: 10.1007/s12072-022-10409-5. Epub 2022 Sep 7.
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.
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).
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 [Formula: see text]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 [Formula: see text]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/m), Q2 (BMI 32.5-35.5 kg/m), Q3 (BMI 35.5-38.8 kg/m) and Q4 (BMI ≥ 38.8 kg/m) 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.
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.
探讨不同肥胖程度受试者内脏脂肪细胞肥大与非酒精性脂肪性肝病（NAFLD）发生发展之间的关联。
收集肥胖受试者的网膜脂肪组织和肝活检组织。根据非酒精性脂肪性肝炎临床研究网络评分系统定义NAFLD。采用病理切片分析测量脂肪细胞大小。脂肪组织胰岛素抵抗（Adipo-IR）计算为空腹胰岛素（pmol/L）×空腹游离脂肪酸浓度（mmol/L）。
共纳入275例肥胖患者，其中158例女性和58例男性患有NAFLD。在女性中，与对照组相比，NAFLD参与者的脂肪细胞大小显著更大（99.37±14.18 vs. 84.14±12.65 [公式：见正文]m，p<0.001）。此外，与非酒精性脂肪肝（NAFL）女性相比，非酒精性脂肪性肝炎（NASH）女性的脂肪细胞更大（101.45±12.77 vs. 95.79±15.80 [公式：见正文]m，p = 0.015）。中介分析表明，脂肪细胞大小通过Adipo-IR影响NAFLD活动评分（b = 0.007 [95%自抽样置信区间0.002，0.013]）。此外，根据BMI四分位数将女性分为：Q1（BMI<32.5 kg/m）、Q2（BMI 32.5-35.5 kg/m）、Q3（BMI 35.5-38.8 kg/m）和Q4（BMI≥38.8 kg/m）。Q1-Q3中NAFLD受试者的网膜脂肪细胞大小更大，但Q4中则不然。男性未观察到类似结果。
我们首次报道，内脏脂肪细胞肥大与轻度至中度肥胖患者的NAFLD发生和进展相关，但与重度肥胖患者无关，这可能由脂肪组织胰岛素抵抗介导。
