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Free fatty acids and insulin resistance.
Curr Opin Clin Nutr Metab Care 2007; 10(2):142-8CO

Abstract

PURPOSE OF REVIEW

Dysregulation of free fatty acid metabolism is a key event responsible for insulin resistance and type 2 diabetes. According to the glucose-fatty acid cycle of Randle, preferential oxidation of free fatty acids over glucose plays a major role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. However, other mechanisms are now described to explain the molecular basis of insulin resistance.

RECENT FINDINGS

Recent studies have suggested that local accumulation of fat metabolites such as ceramides, diacylglycerol or acyl-CoA, inside skeletal muscle and liver, may activate a serine kinase cascade leading to defects in insulin signalling and glucose transport. Inflammation and oxidative stress are also potent mechanisms which could lead to a state of insulin resistance. Finally, modulation of transcription by free fatty acids through their binding to peroxisome proliferator-activated receptors could also contribute to impaired glucose metabolism.

SUMMARY

The increase in free fatty acid flux resulting from increased lipolysis secondary to adipose-tissue insulin resistance induces or aggravates insulin resistance in liver and muscle through direct or indirect (from triglyceride deposits) generation of metabolites, altering the insulin signalling pathway. Alleviating the excess of free fatty acids is a target for the treatment of insulin resistance.

Authors+Show Affiliations

Laboratoire Régional de Nutrition Humaine and EA-948, CHU de Brest et Université de Bretagne Occidentale, Brest, France. jacques.delarue@univ-brest.frNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17285001

Citation

Delarue, Jacques, and Christophe Magnan. "Free Fatty Acids and Insulin Resistance." Current Opinion in Clinical Nutrition and Metabolic Care, vol. 10, no. 2, 2007, pp. 142-8.
Delarue J, Magnan C. Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care. 2007;10(2):142-8.
Delarue, J., & Magnan, C. (2007). Free fatty acids and insulin resistance. Current Opinion in Clinical Nutrition and Metabolic Care, 10(2), pp. 142-8.
Delarue J, Magnan C. Free Fatty Acids and Insulin Resistance. Curr Opin Clin Nutr Metab Care. 2007;10(2):142-8. PubMed PMID: 17285001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Free fatty acids and insulin resistance. AU - Delarue,Jacques, AU - Magnan,Christophe, PY - 2007/2/8/pubmed PY - 2007/5/1/medline PY - 2007/2/8/entrez SP - 142 EP - 8 JF - Current opinion in clinical nutrition and metabolic care JO - Curr Opin Clin Nutr Metab Care VL - 10 IS - 2 N2 - PURPOSE OF REVIEW: Dysregulation of free fatty acid metabolism is a key event responsible for insulin resistance and type 2 diabetes. According to the glucose-fatty acid cycle of Randle, preferential oxidation of free fatty acids over glucose plays a major role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. However, other mechanisms are now described to explain the molecular basis of insulin resistance. RECENT FINDINGS: Recent studies have suggested that local accumulation of fat metabolites such as ceramides, diacylglycerol or acyl-CoA, inside skeletal muscle and liver, may activate a serine kinase cascade leading to defects in insulin signalling and glucose transport. Inflammation and oxidative stress are also potent mechanisms which could lead to a state of insulin resistance. Finally, modulation of transcription by free fatty acids through their binding to peroxisome proliferator-activated receptors could also contribute to impaired glucose metabolism. SUMMARY: The increase in free fatty acid flux resulting from increased lipolysis secondary to adipose-tissue insulin resistance induces or aggravates insulin resistance in liver and muscle through direct or indirect (from triglyceride deposits) generation of metabolites, altering the insulin signalling pathway. Alleviating the excess of free fatty acids is a target for the treatment of insulin resistance. SN - 1363-1950 UR - https://www.unboundmedicine.com/medline/citation/17285001/Free_fatty_acids_and_insulin_resistance_ L2 - http://Insights.ovid.com/pubmed?pmid=17285001 DB - PRIME DP - Unbound Medicine ER -