Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver.

Full Abstract

Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing insulin resistance in muscle, liver, and endothelial cells, contributes to the development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). The mechanism through which FFA induces insulin resistance involves intramyocellular and intrahepatocellular accumulation of triglycerides and diacylglycerol, activation of several serine/threonine kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of insulin signaling. FFA also produces low-grade inflammation in skeletal muscle and liver through activation of nuclear factor-kappaB, resulting in release of several proinflammatory and proatherogenic cytokines. Thus, elevated FFA levels (due to obesity or to high-fat feeding) cause insulin resistance in skeletal muscle and liver, which contributes to the development of T2DM, and produce low-grade inflammation, which contributes to the development of atherosclerotic vascular diseases and NAFLD.

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Author information

Author/s: Boden, Guenther (G);

Affiliation: Division of Endocrinology/Diabetes/Metabolism, Temple University School of Medicine, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140, USA. bodengh(-atsign-)tuhs.temple.edu

Grants: R01-DK58895 (Agency:NIDDK NIH HHS) ; R01-HL-733267 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review

Journal: Current diabetes reports (Curr Diab Rep), published in United States. (Language: eng)

Reference: 2006-Jun; vol 6 (issue 3) : pp 177-81

Dates: Created 2006/08/10; Completed 2006/08/25; Revised 2007/11/14;

PMID: 16898568, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Diabetes Mellitus, Type 2 - physiopathology
Fatty Acids, Nonesterified - blood; physiology
Humans
Inflammation - etiology

Insulin Resistance - physiology
Liver - physiology
Muscle, Skeletal - physiology
Obesity - complications

Associated Chemicals: Fatty Acids, Nonesterified (0)

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