Effects of in vivo phlorizin treatment and in vitro addition of carnitine, propionate, acetate, and 5-tetradecyloxy-2-furoic acid on palmitate metabolism in ovine hepatocytes
Effects of in vivo phlorizin treatment and in vitro addition of carnitine, propionate, acetate, and 5-tetradecyloxy-2-furoic acid on palmitate metabolism in ovine hepatocytes
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DOI：
10.3168/jds.2020-20015
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发表时间：
2021-06-16
影响因子：
3.5
通讯作者：
Drackley, J. K.
中科院分区：
文献类型：
--
作者：
Abbamonte, C. J. Ottemann;Overton, T. R.;Drackley, J. K.
研究了L肉碱、醋酸酯、丙酸和乙酰辅酶A羧化酶抑制剂5-十四氧基-2-呋喃甲酸(TOFA)对根茎苷处理的肝细胞和对照Wethers肝细胞[1-C-14]-棕榈酸酯氧化和酯化的调节作用。我们的假设是：(1)注射根皮苷的绵羊肝细胞中棕榈酸的氧化程度更大；(2)L肉碱能更多地增加注射根皮苷的绵羊肝细胞中棕榈酸的氧化作用；(3)醋酸酯和丙酸可能部分通过乙酰辅酶A羧化酶的作用而减少绵羊肝细胞的氧化。棕榈酸酯代谢在对照细胞和根茎苷处理的Wethers细胞之间没有差别。肉碱增加了棕榈酸酯氧化为CO2和酸溶产物(主要是酮体)，并降低了棕榈酸酯的酯化，但在根茎苷处理的Wethers细胞中，对ASP的氧化增加得更多。在根茎苷治疗的Wethers中，丙酸增加棕榈酸酯氧化为CO2。在对照Wethers中，丙酸增加棕榈酸酯氧化为天冬氨酸，而在根茎苷处理的Wethers中，丙酸则减少氧化为天冬氨酸。丙酸能促进棕榈酸酯的酯化反应生成总酯化产物和甘油三酯，且以根皮苷处理的效果更好。在对照Wethers中，醋酸酯降低了棕榈酸酯的酯化程度，但在根茎苷处理的Wethers中，这种影响变得迟钝。醋酸盐不影响棕榈酸酯的氧化。在丙酸酯存在下，添加TOFA可增加棕榈酸酯的甘油三酯的产量。TOFA与丙酸之间没有相互作用，这表明丙酸不能通过乙酰辅酶A羧基酶胞浆生成甲基丙二酰辅酶A来抑制肉碱棕榈酰转移酶I。综上所述，尽管根茎皂苷体内处理不影响体外培养的绵羊肝细胞对棕榈酸酯的代谢，但根茎皂苷增加了肉碱对棕榈酸酯氧化为天冬氨酸的促进作用和丙酸对棕榈酸氧化为天冬氨酸的抑制作用。乙酰-辅酶A羧基酶对乙酸酯和丙酸酯的代谢不影响棕榈酸酯的氧化或酯化。结果为控制肝细胞中的脂肪酸代谢提供了更多的洞察力。
Modulatory effects of l-carnitine, acetate, propionate, and 5-tetradecyloxy-2-furoic acid (TOFA; an inhibitor of acetyl-CoA carboxylase) on oxidation and esterification of [1-C-14]-palmitate were studied in hepatocytes isolated from phlorizin-treated and control wethers. Our hypotheses were that (1) palmitate oxidation would be greater in hepatocytes from sheep injected with phlorizin; (2) l-carnitine would increase palmitate oxidation more in hepatocytes from sheep injected with phlorizin; and (3) acetate and propionate would decrease oxidation in sheep hepatocytes partly through action of acetyl-CoA carboxylase. Palmitate metabolism did not differ between cells from control and those from phlorizin-treated wethers. Carnitine increased oxidation of palmitate to CO2 and acid-soluble products (ASP; mainly ketone bodies) and decreased esterification of palmitate in isolated hepatocytes from both groups of wethers, but the increase in oxidation to ASP was greater in cells from phlorizin-treated wethers. Propionate increased palmitate oxidation to CO2 in phlorizin-treated wethers. Propionate increased oxidation of palmitate to ASP in control wethers but decreased oxidation to ASP in phlorizin-treated wethers. Propionate increased esterification of palmitate to total esterified products and triglyceride, and the effect was larger in phlorizin-treated wethers. Acetate decreased palmitate esterification to total esterified products in control wethers, but the effect was blunted in phlorizin-treated wethers. Acetate did not affect palmitate oxidation. Addition of TOFA increased production of triglyceride from palmitate in the presence of propionate. The lack of interaction between TOFA and propionate indicates that propionate does not inhibit carnitine palmitoyltransferase I via cytosolic generation of methylmalonyl-CoA by acetyl-CoA carboxylase. In conclusion, although in vivo phlorizin treatment did not affect in vitro metabolism of palmitate by isolated ovine hepatocytes, phlorizin increased the stimulatory effect of carnitine on oxidation of palmitate to ASP and the inhibitory effect of propionate on oxidation of palmitate to ASP. Metabolism of acetate and propionate by acetyl-CoA carboxylase did not affect palmitate oxidation or esterification. Results provide additional insight into control of fatty acid metabolism in hepatocytes.