Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Department of Physiological Sciences, Federal University of Santa Catarina, Florianopolis, Brazil.
Am J Physiol Endocrinol Metab. 2020 Aug 1;319(2):E376-E387. doi: 10.1152/ajpendo.00028.2020. Epub 2020 Jun 16.
White adipose tissue (WAT) dysfunction in obesity is implicated in the onset of whole body insulin resistance. Alterations in mitochondrial bioenergetics, namely impaired mitochondrial respiration and increased mitochondrial reactive oxygen species (mtROS) production, have been suggested to contribute to this metabolic dysregulation. However, techniques investigating mitochondrial function are classically normalized to tissue weight, which may be confounding when considering obesity-related adipocyte hypertrophy. Furthermore, the effect of long-term high-fat diet (HFD) on mtROS in WAT has yet to be elucidated. Therefore, we sought to determine the HFD-mediated temporal changes in mitochondrial respiration and mtROS emission in WAT. C57BL/6N mice received low-fat diet or HFD for 1 or 8 wk and changes in inguinal WAT (iWAT) and epididymal WAT (eWAT) were assessed. While tissue weight-normalized mitochondrial respiration was reduced in iWAT following 8-wk HFD-feeding, this effect was mitigated when adipocyte cell size and/or number were considered. These data suggest HFD does not impair mitochondrial respiratory capacity per adipocyte within WAT. In support of this assertion, within eWAT compensatory increases in lipid-supported and maximal succinate-supported respiration occurred at 8 wk despite cell hypertrophy and increases in WAT inflammation. Although these data suggest impairments in mitochondrial respiration do not contribute to HFD-mediated WAT phenotype, lipid-supported mtROS emission increased following 1-wk HFD in eWAT, while both lipid and carbohydrate-supported mtROS were increased at 8 wk in both depots. Combined, these data establish that while HFD does not impair adipocyte mitochondrial respiratory capacity, increased mtROS is an enduring physiological occurrence within WAT in HFD-induced obesity.
白色脂肪组织（WAT）在肥胖中的功能障碍与全身胰岛素抵抗的发生有关。线粒体生物能量的改变，即线粒体呼吸受损和增加的线粒体活性氧（mtROS）产生，被认为有助于这种代谢失调。然而，研究线粒体功能的技术通常被归一化为组织重量，这在考虑肥胖相关脂肪细胞肥大时可能会产生混淆。此外，长期高脂肪饮食（HFD）对 WAT 中 mtROS 的影响尚未阐明。因此，我们试图确定 HFD 介导的 WAT 中线粒体呼吸和 mtROS 发射的时间变化。C57BL/6N 小鼠接受低脂饮食或 HFD 喂养 1 或 8 周，评估腹股沟 WAT（iWAT）和附睾 WAT（eWAT）的变化。虽然 8 周 HFD 喂养后 iWAT 的组织重量归一化线粒体呼吸减少，但当考虑脂肪细胞大小和/或数量时，这种影响会减轻。这些数据表明，HFD 不会损害 WAT 内每个脂肪细胞的线粒体呼吸能力。支持这一观点，尽管 eWAT 中的细胞肥大和 WAT 炎症增加，但在 8 周时，脂质支持和最大琥珀酸支持的呼吸出现了代偿性增加。尽管这些数据表明线粒体呼吸的损伤不会导致 HFD 介导的 WAT 表型，但在 eWAT 中，HFD 喂养 1 周后，脂质支持的 mtROS 发射增加，而在 8 周时，两个部位的脂质和碳水化合物支持的 mtROS 都增加。综上所述，虽然 HFD 不会损害脂肪细胞线粒体呼吸能力，但增加的 mtROS 是 HFD 诱导肥胖的 WAT 中持久的生理现象。
