Branched short-chain fatty acids modulate glucose and lipid metabolism in primary adipocytes.

Branched short-chain fatty acids modulate glucose and lipid metabolism in primary adipocytes.
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DOI:
10.1080/21623945.2016.1252011
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发表时间:
2016-10
期刊:
影响因子:
3.3
通讯作者:
Degerman E
Degerman E
中科院分区:
生物学4区
文献类型:
--
作者:
Heimann E;Nyman M;Pålbrink AK;Lindkvist-Petersson K;Degerman E

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通过膳食纤维的结肠发酵产生的短链脂肪酸(SCFA),例如乙酸、丙酸和丁酸,已经显示以微摩尔浓度到达体循环。此外,SCFA已在动物模型和人类受试者中被赋予抗肥胖特性。支化SCFA(BSCFA),例如,异丁酸和异戊酸是由支链氨基酸发酵产生的,支链氨基酸由到达结肠的未消化蛋白质产生。然而,BSCFAs在能量代谢方面的研究很少。本文主要研究了异丁酸和异戊酸对原代大鼠和人脂肪细胞糖脂代谢的影响。BSCFAs抑制cAMP介导的脂解和胰岛素刺激的从头脂肪生成在10 mM,而异丁酸增强胰岛素刺激的葡萄糖摄取的所有浓度(1,3和10 mM)在大鼠脂肪细胞。对于人脂肪细胞,仅SCFA在10 mM下抑制脂解。在两种体外模型中,BSCFAs和SCFAs降低了激素敏感性脂肪酶(脂解中的限速酶)的磷酸化。此外,与胰岛素相反,BSCFA和SCFA在大鼠脂肪细胞中在磷脂酰肌醇3激酶抑制剂渥曼青霉素和磷酸二酯酶3抑制剂OPC 3911存在下抑制脂解。此外,BSCFA和SCFA减少胰岛素介导的蛋白激酶B磷酸化。总之,BSCFAs对脂肪细胞脂质和葡萄糖代谢有影响,这有助于改善代谢紊乱个体的胰岛素敏感性。
Short-chain fatty acids (SCFAs), e.g. acetic acid, propionic acid and butyric acid, generated through colonic fermentation of dietary fibers, have been shown to reach the systemic circulation at micromolar concentrations. Moreover, SCFAs have been conferred anti-obesity properties in both animal models and human subjects. Branched SCFAs (BSCFAs), e.g., isobutyric and isovaleric acid, are generated by fermentation of branched amino acids, generated from undigested protein reaching colon. However, BSCFAs have been sparsely investigated when referring to effects on energy metabolism. Here we primarily investigate the effects of isobutyric acid and isovaleric acid on glucose and lipid metabolism in primary rat and human adipocytes. BSCFAs inhibited both cAMP-mediated lipolysis and insulin-stimulated de novo lipogenesis at 10 mM, whereas isobutyric acid potentiated insulin-stimulated glucose uptake by all concentrations (1, 3 and 10 mM) in rat adipocytes. For human adipocytes, only SCFAs inhibited lipolysis at 10 mM. In both in vitro models, BSCFAs and SCFAs reduced phosphorylation of hormone sensitive lipase, a rate limiting enzyme in lipolysis. In addition, BSCFAs and SCFAs, in contrast to insulin, inhibited lipolysis in the presence of wortmannin, a phosphatidylinositide 3-kinase inhibitor and OPC3911, a phosphodiesterase 3 inhibitor in rat adipocytes. Furthermore, BSCFAs and SCFAs reduced insulin-mediated phosphorylation of protein kinase B. To conclude, BSCFAs have effects on adipocyte lipid and glucose metabolism that can contribute to improved insulin sensitivity in individuals with disturbed metabolism.
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期刊: ADIPOCYTE
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