Department of Biochemistry and Molecular Biomedicine, CIBER Fisiopatología de la Obesidad y Nutrición, Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain.
Institut de Recerca Sant Joan de Déu, Barcelona, Spain.
J Intern Med. 2018 Nov;284(5):492-504. doi: 10.1111/joim.12803. Epub 2018 Jul 16.
Many of the comorbidities of obesity, including type 2 diabetes and cardiovascular diseases, are related to the low-grade chronic inflammation of white adipose tissue. Under white adipocyte stress, local infiltration of immune cells and enhanced production of pro-inflammatory cytokines together reduce metabolic flexibility and lead to insulin resistance in obesity. Whereas white adipocytes act in energy storage, brown and beige adipocytes specialize in energy expenditure. Brown and beige activity protects against obesity and associated metabolic disorders, such as hyperglycaemia and hyperlipidaemia. Compared to white fat, brown adipose tissue depots are less susceptible to developing local inflammation in response to obesity; however, strong obesogenic insults ultimately induce a locally pro-inflammatory environment in brown fat. This condition directly alters the thermogenic activity of brown fat by impairing its energy expenditure mechanism and uptake of glucose for use as a fuel substrate. Pro-inflammatory cytokines also impair beige adipogenesis, which occurs mainly in subcutaneous adipose tissue. There is evidence that inflammatory processes occurring in perivascular adipose tissues alter their brown-versus-white plasticity, impair the extent of browning in these depots and favour the local release of vasculature damaging signals. In summary, the targeting of brown and beige adipose tissues by pro-inflammatory signals and the subsequent impairment of their thermogenic and metabolite draining activities appears to represent obesity-driven disturbances that contribute to metabolic syndrome and cardiovascular alterations in obesity.
肥胖的许多合并症，包括 2 型糖尿病和心血管疾病，都与白色脂肪组织的低度慢性炎症有关。在白色脂肪细胞应激下，免疫细胞的局部浸润和促炎细胞因子的产生增加共同降低了代谢灵活性，导致肥胖中的胰岛素抵抗。虽然白色脂肪细胞的作用是储存能量，但棕色和米色脂肪细胞则专门用于消耗能量。棕色和米色脂肪的活动可以预防肥胖和相关的代谢紊乱，如高血糖和高血脂。与白色脂肪相比，棕色脂肪组织不易受到肥胖的局部炎症反应的影响；然而，强烈的肥胖因素最终会导致棕色脂肪中产生局部促炎环境。这种情况通过损害其能量消耗机制和葡萄糖摄取作为燃料底物直接改变棕色脂肪的产热活性。促炎细胞因子还会损害主要发生在皮下脂肪组织中的米色脂肪生成。有证据表明，发生在血管周围脂肪组织中的炎症过程改变了它们的棕色与白色之间的可塑性，损害了这些脂肪组织中褐色化的程度，并有利于局部释放损害血管的信号。总之，促炎信号靶向棕色和米色脂肪组织，随后损害它们的产热和代谢产物排出活动，似乎代表了肥胖驱动的紊乱，导致代谢综合征和肥胖中的心血管改变。
