University of the Balearic Islands and Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Palma de Mallorca 07122, Spain.
Endocrinology. 2009 Dec;150(12):5341-50. doi: 10.1210/en.2009-0466. Epub 2009 Oct 16.
This study aimed to assess the effects of carbohydrate (CHO) and fat intake on the expression of key genes related with nutrient partitioning and metabolism in main tissues involved in energy metabolism (white adipose tissue, liver, and skeletal muscle). Rats were studied under different conditions: feeding state, 24 h fasting, and 12 h refeeding after 24 h fasting with isocaloric amounts of CHO or fat. Fat, but not CHO, refeeding was associated with an increase in serum and liver triglyceride content. Main changes in gene expression elicited by CHO compared with fat refeeding were: 1) higher expression levels of genes related with lipogenesis (PPARgamma2, ChREBP, FAS), glucose uptake and metabolism (GLUT4, HKII), fatty acid uptake (LPL, CD36), and lipolysis (ATGL, HSL) in white adipose tissue; 2) higher expression levels of genes related with lipogenesis (FAS, SCD1) but lower ones related with fatty acid uptake (CD36) and oxidation (PPARalpha, CPT1, PDK4) in liver; and 3) higher expression levels of GLUT4 but lower ones related with fatty acid oxidation (PDK4 and UCP3) in muscle. It is worth mentioning that both CHO and fat refeeding resulted in a robust increase in both hepatic mRNA and circulating levels of fibroblast growth factor-21, compared with fasted levels. In summary, these results, showing marked differences in gene expression after CHO and fat refeeding, can explain diet-associated differences in fuel handling and partitioning between tissues; in addition, a role of fibroblast growth factor-21 in metabolic adaptations, not only in the ketotic state but also to face an unbalanced nutritional situation, is suggested.
本研究旨在评估碳水化合物 (CHO) 和脂肪摄入对与营养分配和代谢相关的关键基因在参与能量代谢的主要组织（白色脂肪组织、肝脏和骨骼肌）中的表达的影响。在不同条件下研究了大鼠：进食状态、24 小时禁食以及 24 小时禁食后 12 小时用等热量的 CHO 或脂肪进行再喂养。与脂肪再喂养相比，脂肪而非 CHO 再喂养与血清和肝脏甘油三酯含量增加有关。与脂肪再喂养相比，CHO 引起的基因表达的主要变化为：1）白色脂肪组织中与脂肪生成（PPARγ2、ChREBP、FAS）、葡萄糖摄取和代谢（GLUT4、HKII）、脂肪酸摄取（LPL、CD36）和脂肪分解（ATGL、HSL）相关的基因表达水平升高；2）肝脏中与脂肪生成（FAS、SCD1）相关的基因表达水平升高，但与脂肪酸摄取（CD36）和氧化（PPARα、CPT1、PDK4）相关的基因表达水平降低；3）肌肉中 GLUT4 表达水平升高，但与脂肪酸氧化（PDK4 和 UCP3）相关的基因表达水平降低。值得注意的是，与禁食水平相比，CHO 和脂肪再喂养均导致肝 mRNA 和循环中纤维母细胞生长因子 21 的水平显著增加。总之，这些结果表明，CHO 和脂肪再喂养后的基因表达存在明显差异，可以解释饮食相关的组织间燃料处理和分配差异；此外，还提示纤维母细胞生长因子 21 在代谢适应中的作用，不仅在酮症状态下，而且在面对不平衡的营养状况时也是如此。
