title: Muscle-specific inflammation induced by MCP-1 overexpression does not affect whole-body insulin sensitivity in mice.
abstract: OBJECTIVE
  Obesity is associated with a state of chronic low-grade inflammation that is believed to contribute to the development of skeletal muscle insulin resistance. However, the extent to which local and systemic elevation of cytokines, such as monocyte chemoattractant protein 1 (MCP-1), interferes with the action of insulin and promotes insulin resistance and glucose intolerance in muscle remains unclear. Here, we aim to investigate the effect of muscle-specific overexpression of MCP-1 on insulin sensitivity and glucose tolerance in lean and obese mice.
  
  
  METHODS
  We used Mck-Mcp-1 transgenic (Tg) mice characterised by muscle-specific overexpression of Mcp-1 (also known as Ccl2) and elevated plasma MCP-1 levels. Mice were fed either chow or high-fat diet for 10 weeks. Numerous metabolic variables were measured, including glucose and insulin tolerance tests, muscle insulin signalling and plasma NEFA, triacylglycerol, cholesterol, glucose and insulin.
  
  
  RESULTS
  Despite clearly promoting skeletal muscle inflammation, muscle-specific overexpression of Mcp-1 did not influence glucose tolerance or insulin sensitivity in either lean chow-fed or diet-induced obese mice. In addition, plasma NEFA, triacylglycerol, cholesterol, glucose and insulin were not affected by MCP-1 overexpression. Finally, in vivo insulin-induced Akt phosphorylation in skeletal muscle did not differ between Mcp-1-Tg and wild-type mice.
  
  
  CONCLUSIONS
  We show that increased MCP-1 production in skeletal muscle and concomitant elevated MCP-1 levels in plasma promote inflammation in skeletal muscle but do not influence insulin signalling and have no effect on insulin resistance and glucose tolerance in lean and obese mice. Overall, our data argue against MCP-1 promoting insulin resistance in skeletal muscle and raise questions about the impact of inflammation on insulin sensitivity in muscle.
authors.affiliation: Molecular Cancer Research and Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Inkie J A
authors.initials: IJ
authors.lastname: Evers-van Gogh
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, the Netherlands.
authors.forename: Antwi-Boasiako
authors.initials: AB
authors.lastname: Oteng
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, the Netherlands.
authors.forename: Sheril
authors.initials: S
authors.lastname: Alex
authors.affiliation: Molecular Cancer Research and Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Hamers
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, the Netherlands.
authors.forename: Milene
authors.initials: M
authors.lastname: Catoire
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, the Netherlands.
authors.forename: Rinke
authors.initials: R
authors.lastname: Stienstra
authors.affiliation: Molecular Cancer Research and Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Kalkhoven
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, the Netherlands. sander.kersten@wur.nl.
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2
keywords: Inflammation; Insulin resistance; MCP-1; Muscle-specific; Myokine; Obesity; Type 2 diabetes