Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Int J Mol Sci. 2022 Oct 21;23(20):12680. doi: 10.3390/ijms232012680.
Obesity impacts 650 million individuals globally, often co-occurring with metabolic syndrome. Though many obese individuals experience metabolic abnormalities (metabolically unhealthy obese [MUO]), ~30% do not (metabolically healthy obese [MHO]). Conversely, >10% of lean individuals are metabolically unhealthy (MUL). To evaluate the physiologic drivers of these phenotypes, a 44-animal African green monkey cohort was selected using metabolic syndrome risk criteria to represent these four clinically defined health groups. Body composition imaging and subcutaneous adipose tissue (SQ AT) biopsies were collected. Differences in adipocyte size, macrophage subtype distribution, gene expression, vascularity and fibrosis were analyzed using digital immunohistopathology, unbiased RNA-seq, endothelial CD31, and Masson’s trichrome staining, respectively. MHO AT demonstrated significant increases in M2 macrophages (p = 0.02) and upregulation of fatty acid oxidation-related terms and transcripts, including FABP7 (p = 0.01). MUO AT demonstrated downregulation of these factors and co-occurring upregulation of immune responses. These changes occurred without differences in AT distributions, adipocyte size, AT endothelial cells, collagen I deposition, or circulating cytokine levels. Without unhealthy diet consumption, healthy obesity is defined by an increased SQ AT M2/M1 macrophage ratio and lipid handling gene expression. We highlight M2 macrophages and fatty acid oxidation as targets for improving metabolic health with obesity.
肥胖影响全球 6.5 亿人，常伴有代谢综合征。尽管许多肥胖个体存在代谢异常（代谢不健康肥胖 [MUO]），但约 30%的人不存在（代谢健康肥胖 [MHO]）。相反，超过 10%的瘦个体代谢不健康（MUL）。为了评估这些表型的生理驱动因素，选择了一个由 44 只非洲绿猴组成的队列，这些猴子采用代谢综合征风险标准，代表了这四个临床定义的健康组。收集了身体成分成像和皮下脂肪组织（SQ AT）活检。使用数字免疫组织病理学、无偏 RNA-seq、内皮细胞 CD31 和 Masson 三色染色分别分析了脂肪细胞大小、巨噬细胞亚型分布、基因表达、血管生成和纤维化的差异。MHO AT 表现出 M2 巨噬细胞显著增加（p = 0.02），以及脂肪酸氧化相关术语和转录物的上调，包括 FABP7（p = 0.01）。MUO AT 表现出这些因子的下调和伴随的免疫反应上调。这些变化发生在没有脂肪组织分布、脂肪细胞大小、脂肪组织内皮细胞、胶原 I 沉积或循环细胞因子水平差异的情况下。在没有不健康饮食摄入的情况下，健康肥胖的特征是 SQ AT 中 M2/M1 巨噬细胞比例增加和脂质处理基因表达增加。我们强调 M2 巨噬细胞和脂肪酸氧化作为改善肥胖代谢健康的目标。
