Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus [T2DM] onset. It occurs as a result of disturbances in lipid metabolism and increased levels of circulating free fatty acids [FFAs]. FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased fatty acid flux has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes development. FFAs appear to cause this defect in glucose transport by inhibiting insulin –stimulated tyrosine phosphorylation of insulin receptor substrate-1 [IRS-1] and IRS-1 associated phosphatidyl-inositol 3-kinase activity. A number of different metabolic abnormalities may increase intramyocellular or intrahepatic fatty acid metabolites that induce insulin resistance through different cellular mechanisms. The current review point out the link between enhanced FFAs flux and activation of PKC and how it impacts on both the insulin signaling in muscle and liver as shown from our laboratory data and highlighting the involvement of the inflammatory pathways importance. This embarks the importance of measuring the inflammatory biomarkers in clinical settings.

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Essential Fatty Acid Status and Characteristics Associated with Colostrum-Deprived Gnotobiotic and Conventional Lambs. Growth, Organ Development, Cell Membrane Integrity and Factors Associated with Lower Bowel Function

Journal of Animal Science ◽

10.2527/jas1984.584971x ◽

1984 ◽

Vol 58 (4) ◽

pp. 971-978 ◽

Cited By ~ 1

Author(s):

G. Bruckner ◽

K. K. Grunewald ◽

R. E. Tucker ◽

G. E. Mitchell

Keyword(s):

Fatty Acid ◽

Cell Membrane ◽

Essential Fatty Acid ◽

Membrane Integrity ◽

Bowel Function ◽

Fatty Acid Status ◽

Cell Membrane Integrity ◽

Lower Bowel ◽

Factors Associated ◽

Acid Status

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Effect of early introduction of formula vs fat-free parenteral nutrition on essential fatty acid status of preterm infants

American Journal of Clinical Nutrition ◽

10.1093/ajcn/54.1.93 ◽

1991 ◽

Vol 54 (1) ◽

pp. 93-97 ◽

Cited By ~ 31

Author(s):

K D Foote ◽

M J MacKinnon ◽

S M Innis

Keyword(s):

Fatty Acid ◽

Parenteral Nutrition ◽

Essential Fatty Acid ◽

Preterm Infants ◽

Fatty Acid Status ◽

Early Introduction ◽

Acid Status ◽

Essential Fatty Acid Status

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Peroxisome Proliferator-Activated Receptor γ and Adipose Tissue—Understanding Obesity-Related Changes in Regulation of Lipid and Glucose Metabolism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-1268 ◽

2006 ◽

Vol 92 (2) ◽

pp. 386-395 ◽

Cited By ~ 297

Author(s):

Arya M. Sharma ◽

Bart Staels

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Adipose Tissue ◽

Fatty Acid ◽

Endocrine Function ◽

Low Grade ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor

Abstract Context: Adipose tissue is a metabolically dynamic organ, serving as a buffer to control fatty acid flux and a regulator of endocrine function. In obese subjects, and those with type 2 diabetes or the metabolic syndrome, adipose tissue function is altered (i.e. adipocytes display morphological differences alongside aberrant endocrine and metabolic function and low-grade inflammation). Evidence Acquisition: Articles on the role of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue of healthy individuals and those with obesity, metabolic syndrome, or type 2 diabetes were sourced using MEDLINE (1990–2006). Evidence Synthesis: Articles were assessed to provide a comprehensive overview of how PPARγ-activating ligands improve adipose tissue function, and how this links to improvements in insulin resistance and the progression to type 2 diabetes and atherosclerosis. Conclusions: PPARγ is highly expressed in adipose tissue, where its activation with thiazolidinediones alters fat topography and adipocyte phenotype and up-regulates genes involved in fatty acid metabolism and triglyceride storage. Furthermore, PPARγ activation is associated with potentially beneficial effects on the expression and secretion of a range of factors, including adiponectin, resistin, IL-6, TNFα, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and angiotensinogen, as well as a reduction in plasma nonesterified fatty acid supply. The effects of PPARγ also extend to macrophages, where they suppress production of inflammatory mediators. As such, PPARγ activation appears to have a beneficial effect on the relationship between the macrophage and adipocyte that is distorted in obesity. Thus, PPARγ-activating ligands improve adipose tissue function and may have a role in preventing progression of insulin resistance to diabetes and endothelial dysfunction to atherosclerosis.

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