Retinol-binding protein 4 as a risk factor for cholesterol gallstone formation

Mol Cell Biochem. 2013 May;377(1-2):219-27. doi: 10.1007/s11010-013-1587-9. Epub 2013 Feb 19.


Retinol-binding protein 4 (RBP4) is closely associated with a variety of abnormal glycolipid metabolism diseases such as insulin resistance, obesity, diabetes mellitus, and metabolic syndrome. Part 1 Twenty-four male C57/B6 mice were randomly divided into a normal control group (group C, n = 8), a gallstone group (group G, n = 8), and a medication group (group M, n = 8). Serum RBP4 levels were measured by ELISA. RBP4 expression in liver and adipose tissue was detected by western blotting. The transcription of RBP-4 mRNA, PPAR-γ mRNA in the liver was measured using real-time PCR. The incidences of gallstone formation were 0/8 (group C), 7/8 (group G), and 2/8 (group M) (p < 0.01). Group G had significantly higher body weight, adipose mass, fasting glucose (FG), serum RBP4, total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) than group C. In group M, pioglitazone decreased body weight, adipose mass, levels of serum RBP4, FG, TC, and TG, and it increased levels of HDL-C. Pioglitazone downregulated RBP4 expression in hepatic and adipose tissue and prevented decreases in PPAR-γmRNA levels induced by lithogenic diet. Part 2 Metabolism indices, including serum RBP4, FG, TC, TG, HDL-C, low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) of 110 human cholesterol gallstone patients and 73 healthy controls were collected for further analysis. Patients with gallstones had elevated levels of serum RBP4, FG, TC, TG, ALT, and AST, and had decreased HDL-C levels compared to those of healthy controls. Elevated RBP4 is associated with the morbidity of cholesterol gallstones and metabolic syndrome. RBP4 may play an important role in the course of cholesterol gallstone formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Case-Control Studies
  • Cholesterol / metabolism*
  • Down-Regulation / drug effects
  • Female
  • Gallstones / blood*
  • Glycolipids / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Lipid Metabolism / drug effects
  • Lipoproteins, HDL / blood
  • Lipoproteins, LDL
  • Liver / metabolism
  • Male
  • Metabolic Syndrome / blood
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Pioglitazone
  • Retinol-Binding Proteins, Plasma / genetics
  • Retinol-Binding Proteins, Plasma / metabolism*
  • Retrospective Studies
  • Risk Factors
  • Spectroscopy, Fourier Transform Infrared
  • Thiazolidinediones / pharmacology
  • Young Adult


  • Glycolipids
  • Hypoglycemic Agents
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma
  • Thiazolidinediones
  • Cholesterol
  • Pioglitazone