Obesity is accompanied by numerous systemic and tissue-specific derangements, including systemic inflammation, insulin resistance, and mitochondrial abnormalities in skeletal muscle. Despite growing recognition that adipose tissue dysfunction plays a role in obesity-related disorders, the relationship between adipose tissue inflammation and other pathological features of obesity is not well-understood. We assessed macrophage populations and measured the expression of inflammatory cytokines in abdominal adipose tissue biopsies in 39 non-diabetic adults across a range of body mass indexes (BMI 20.5-45.8 kg/m²). Skeletal muscle biopsies were used to evaluate mitochondrial respiratory capacity, ATP production capacity, coupling, and reactive oxygen species production. Insulin sensitivity (S_I) and beta cell responsivity were determined from test meal postprandial glucose, insulin, c-peptide, and triglyceride kinetics. We examined the relationships between adipose tissue inflammatory markers, systemic inflammatory markers, S_I, and skeletal muscle mitochondrial physiology. BMI was associated with increased adipose tissue and systemic inflammation, reduced S_I, and reduced skeletal muscle mitochondrial oxidative capacity. Adipose-resident macrophage numbers were positively associated with circulating inflammatory markers, including tumor necrosis factor-α (TNFα) and C-reactive protein (CRP). Local adipose tissue inflammation and circulating concentrations of TNFα and CRP were negatively associated with S_I, and circulating concentrations of TNFα and CRP were also negatively associated with skeletal muscle oxidative capacity. These results demonstrate that obese humans exhibit increased adipose tissue inflammation concurrently with increased systemic inflammation, reduced insulin sensitivity, and reduced muscle oxidative capacity, and suggest that adipose tissue and systemic inflammation may drive obesity-associated metabolic derangements.

中文翻译：

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脂肪组织巨噬细胞群和炎症与肥胖患者的全身炎症和胰岛素抵抗有关

肥胖伴随着许多全身性和组织特异性紊乱，包括全身性炎症、胰岛素抵抗和骨骼肌中的线粒体异常。尽管人们越来越认识到脂肪组织功能障碍在肥胖相关疾病中发挥作用，但脂肪组织炎症与肥胖的其他病理特征之间的关系尚不清楚。我们评估了巨噬细胞群，并测量了 39 名非糖尿病成人在一系列体重指数（BMI 20.5-45.8 kg/m ²）的腹部脂肪组织活检中炎症细胞因子的表达。骨骼肌活检用于评估线粒体呼吸能力、ATP 生产能力、耦合和活性氧物质的产生。胰岛素敏感性（_SI) 和 β 细胞反应性由测试餐后葡萄糖、胰岛素、c 肽和甘油三酯动力学确定。_我们检查了脂肪组织炎症标志物、全身炎症标志物、SI和骨骼肌线粒体生理学之间的关系。BMI 与脂肪组织和全身炎症增加、SI_降低和骨骼肌线粒体氧化能力降低有关。脂肪驻留巨噬细胞数量与循环炎症标志物呈正相关，包括肿瘤坏死因子-α (TNFα) 和 C 反应蛋白 (CRP)。局部脂肪组织炎症和循环的 TNFα 和 CRP 浓度与 S _{I呈负相关}，并且循环中的 TNFα 和 CRP 浓度也与骨骼肌氧化能力呈负相关。这些结果表明，肥胖的人表现出脂肪组织炎症增加，同时全身炎症增加、胰岛素敏感性降低和肌肉氧化能力降低，并表明脂肪组织和全身炎症可能导致肥胖相关的代谢紊乱。