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Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
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Deficiency in monocyte chemoattractant protein-1 modifies lipid and glucose metabolism

Anna Rull1, Joan Carles Escolà-Gil, Josep Julve

  • 1Centre de Recerca Biomèdica, Institut de Recerca en Ciències de la Salut (IRCIS), Hospital Universitari de Sant Joan, C/. Sant Joan s/n, 43201-Reus, Spain.

Experimental and Molecular Pathology
|October 9, 2007
PubMed

Insights

Mice lacking MCP-1 (monocyte chemoattractant protein-1) and LDL receptors showed impaired lipoprotein clearance and glucose tolerance. These findings highlight MCP-1

Area of Science:

  • Metabolic research
  • Immunology
  • Genetics

Background:

  • Monocyte chemoattractant protein-1 (MCP-1/CCL2) is primarily known for its role in monocyte recruitment.
  • Dysregulation of lipid and glucose metabolism is a hallmark of metabolic syndrome.
  • Genetic mouse models are crucial for dissecting complex biological pathways.

Purpose of the Study:

  • To investigate the role of MCP-1 deficiency in hyperlipidemia and metabolic derangements.
  • To determine if MCP-1 influences lipoprotein clearance, glucose tolerance, and obesity development.
  • To explore the broader metabolic functions of MCP-1 beyond its chemoattractant properties.

Main Methods:

  • Utilizing a mouse model with combined deficiency in MCP-1 and LDL receptor (MCP-1(-/-)LDLr(-/-)).
  • Comparing metabolic parameters (lipoprotein clearance, glucose tolerance, fatty acid delivery, obesity) between MCP-1(-/-)LDLr(-/-) mice and LDLr(-/-) control mice.
  • Assessing responses to regular chow and diets high in fat and cholesterol.

Main Results:

  • MCP-1(-/-)LDLr(-/-) mice exhibited decreased lipoprotein clearance and impaired glucose tolerance compared to LDLr(-/-) mice on regular chow.
  • MCP-1 deficiency conferred partial resistance to diet-induced alterations in glucose and lipid metabolism.
  • MCP-1(-/-)LDLr(-/-) mice were less susceptible to diet-induced obesity.

Conclusions:

  • MCP-1 plays a significant, previously underappreciated role in regulating glucose and lipid metabolism.
  • The function of MCP-1/CCL2 extends beyond its known chemoattractant activity, indicating complex metabolic regulatory roles.
  • Further research is needed to fully elucidate MCP-1's influence on metabolic consequences of inflammation before considering it as a therapeutic target.

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