Response to carbohydrate and fat refeeding in the expression of genes involved in nutrient partitioning and metabolism: striking effects on fibroblast growth factor-21 induction

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Animals
  • Blood Glucose / metabolism
  • CD36 Antigens / genetics
  • Dietary Carbohydrates / administration & dosage
  • Dietary Carbohydrates / pharmacology*
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology*
  • Energy Metabolism / genetics*
  • Fibroblast Growth Factors / blood
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation / drug effects*
  • Glucose Transporter Type 4 / genetics
  • Insulin / blood
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / metabolism
  • Lipogenesis / genetics
  • Lipolysis / genetics
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Nutritional Physiological Phenomena / drug effects
  • Protein Serine-Threonine Kinases / genetics
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / blood


  • Blood Glucose
  • CD36 Antigens
  • Cd36 protein, rat
  • Dietary Carbohydrates
  • Dietary Fats
  • Glucose Transporter Type 4
  • Insulin
  • Pdk4 protein, rat
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Slc2a4 protein, rat
  • Triglycerides
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Protein Serine-Threonine Kinases