The Expression of Genes Related to Reverse Cholesterol Transport and Leptin Receptor Pathways in Peripheral Blood Mononuclear Cells Are Decreased in Morbid Obesity and Related to Liver Function

Int J Mol Sci. 2024 Jul 9;25(14):7549. doi: 10.3390/ijms25147549.

Abstract

Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects. In the LXRα pathway, LXRα, ABCA1, and ABCG1 mRNA expressions were decreased in MO compared to non-obese subjects (p < 0.001, respectively). Ob-Rb was decreased (p < 0.001), whereas Sam68 was increased (p < 0.001) in MO. RYGB did not change mRNA gene expressions. In the MO group, the LXRα pathway (LXRα/ABCA1/ABCG1) negatively correlated with obesity-related variables (weight, body mass index, and hip), inflammation (C-reactive protein), and liver function (alanine-aminotransferase, alkaline phosphatase, and fatty liver index), and positively with serum albumin. In the Ob-R pathway, Ob-Rb and Sam68 negatively correlated with alanine-aminotransferase and positively with albumin. The alteration of LXRα and Ob-R pathways may play an important role in NAFLD development in MO. It is possible that MO patients may require more than 6 months following RYBGB to normalize gene expression related to reverse cholesterol transport or leptin responsiveness.

Keywords: ABCA1; ABCG1; LXRα; Ob-R; Roux-en-Y gastric bypass; bariatric surgery; obesity.

MeSH terms

  • ATP Binding Cassette Transporter 1* / genetics
  • ATP Binding Cassette Transporter 1* / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Biological Transport
  • Cholesterol* / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Leukocytes, Mononuclear* / metabolism
  • Liver X Receptors* / genetics
  • Liver X Receptors* / metabolism
  • Liver* / metabolism
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Obesity, Morbid* / genetics
  • Obesity, Morbid* / metabolism
  • Obesity, Morbid* / surgery
  • Receptors, Leptin* / genetics
  • Receptors, Leptin* / metabolism
  • Signal Transduction

Substances

  • Receptors, Leptin
  • Cholesterol
  • Liver X Receptors
  • ATP Binding Cassette Transporter 1
  • ABCA1 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ABCG1 protein, human
  • NR1H3 protein, human
  • LEPR protein, human
  • Adaptor Proteins, Signal Transducing