Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 501890
Title Muscle-specific inflammation induced by MCP-1 overexpression does not affect whole-body insulin sensitivity in mice
Author(s) Evers-van Gogh, Inkie J.A.; Oteng, Antwi Boasiako; Alex, Sheril; Hamers, Nicole; Catoire, Milene; Stienstra, Rinke; Kalkhoven, Eric; Kersten, Sander
Source Diabetologia 59 (2016)3. - ISSN 0012-186X - p. 624 - 633.
DOI https://doi.org/10.1007/s00125-015-3822-2
Department(s) Chair Nutrition Metabolism and Genomics
Human Nutrition (HNE)
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2016
Keyword(s) Inflammation - Insulin resistance - MCP-1 - Muscle-specific - Myokine - Obesity - Type 2 diabetes
Abstract

Aims/hypothesis: 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/interpretation: 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.

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