Rotondo Floriana, Ho-Palma Ana Cecilia, Remesar Xavier, Fernández-López José Antonio, Romero María Del Mar, Alemany Marià
Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Faculty of Biology, Barcelona, Spain.
Institute of Biomedicine, University of Barcelona, Barcelona, Spain.
PeerJ. 2018 Aug 10;6:e5440. doi: 10.7717/peerj.5440. eCollection 2018.
Adult rat epididymal adipocytes are able to convert large amounts of glucose to lactate and glycerol. However, fatty acid efflux is much lower than that expected from glycerol levels if they were the product of lipolysis. Use of glucose for lipogenesis is limited, in contrast with the active glycolysis-derived lactate (and other 3-carbon substrates). In this study, we analyzed whether white adipose tissue (WAT) site and sex affect these processes.
Mature adipocytes from perigonadal, mesenteric and subcutaneous WAT of female and male rats were isolated, and incubated with 7 or 14 mM glucose during 1 or 2 days. Glucose consumption, metabolite efflux and gene expression of glycolytic and lipogenesis-related genes were measured.
The effects of medium initial glucose concentration were minimal on most parameters studied. Sex-induced differences that were more extensive; however, the most marked, distinct, effects between WAT sites, were dependent on the time of incubation. In general, the production of lactate was maintained during the incubation, but glycerol release rates increased with time, shifting from a largely glycolytic origin to its triacylglycerol (TAG) lipolytic release. Glycerol incorporation was concurrent with increased TAG turnover: lipolytic glycerol was selectively secreted, while most fatty acids were recycled again into TAG. Fatty acid efflux increased with incubation, but was, nevertheless, minimal compared with that of glycerol. Production of lactate and glycerol from glucose were maximal in mesenteric WAT.
Female rats showed a higher adipocyte metabolic activity than males. In mesenteric WAT, gene expression (and substrate efflux) data suggested that adipocyte oxidation of pyruvate to acetyl-CoA was higher in females than in males, with enhanced return of oxaloacetate to the cytoplasm for its final conversion to lactate. WAT site differences showed marked tissue specialization-related differences. Use of glucose for lipogenesis was seriously hampered over time, when TAG turnover-related lipolysis was activated. We postulate that these mechanisms may help decrease glycaemia and fat storage, producing, instead, a higher availability of less-regulated 3-carbon substrates, used for energy elsewhere.
成年大鼠附睾脂肪细胞能够将大量葡萄糖转化为乳酸和甘油。然而，如果甘油是脂解产物，脂肪酸流出量远低于甘油水平所预期的量。与活跃的糖酵解衍生乳酸（和其他三碳底物）相比，葡萄糖用于脂肪生成的量有限。在本研究中，我们分析了白色脂肪组织（WAT）部位和性别是否会影响这些过程。
分离雌性和雄性大鼠性腺周围、肠系膜和皮下WAT的成熟脂肪细胞，并在1或2天内用7或14 mM葡萄糖孵育。测量葡萄糖消耗、代谢物流出以及糖酵解和脂肪生成相关基因的基因表达。
培养基初始葡萄糖浓度对大多数研究参数的影响最小。性别诱导的差异更为广泛；然而，WAT部位之间最显著、明显的影响取决于孵育时间。一般来说，孵育期间乳酸的产生保持不变，但甘油释放率随时间增加，从主要来源于糖酵解转变为其甘油三酯（TAG）脂解释放。甘油掺入与TAG周转率增加同时发生：脂解甘油被选择性分泌，而大多数脂肪酸再次循环到TAG中。脂肪酸流出量随孵育增加，但与甘油相比仍然很低。肠系膜WAT中葡萄糖产生乳酸和甘油的量最大。
雌性大鼠的脂肪细胞代谢活性高于雄性。在肠系膜WAT中，基因表达（和底物流出）数据表明，雌性脂肪细胞中丙酮酸氧化为乙酰辅酶A的水平高于雄性，草酰乙酸返回细胞质最终转化为乳酸的过程增强。WAT部位差异显示出与组织特异性相关的显著差异。当与TAG周转相关的脂解被激活时，随着时间的推移，葡萄糖用于脂肪生成受到严重阻碍。我们推测，这些机制可能有助于降低血糖和脂肪储存，转而产生更多可用于其他部位能量的、调控较少的三碳底物。
