Abstract
Free fatty acids are the major lipid fuel of the body. Dysregulation of adipose tissue
lipolysis results in increased plasma free fatty acid concentrations, and via that
mechanism contributes to insulin resistance in obesity and type 2 diabetes mellitus.
Adipose tissue hormone sensitive lipase is thought to be responsible for the production
of the majority of free fatty acids. However, a separate contribution comes from the
action of endothelial lipases, especially lipoprotein lipase, on triglyceride-rich
lipoproteins via a process known as spillover. The primary substrate for spillover
appears to be chylomicrons derived from dietary fat. The spillover of fatty acids
into the free fatty acid pool varies from one tissue to another. For example, spillover
is low (∼14%) in the forearm of healthy volunteers, suggesting that triglyceride fatty
acid storage is relatively efficient in skeletal muscle. In contrast, spillover appears
to be higher in adipose tissue and may also be higher in the splanchnic bed, based
on preliminary data. If systemic spillover is increased in insulin resistant states
such as diabetes, this could represent a mechanism contributing to the abnormal increases
in plasma concentrations of free fatty acids in that condition.
Key words
FFA - chylomicrons - kinetics
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Correspondence
J. M. MilesMD
Endocrine Research Unit
Mayo Clinic
Rochester
55905 MN
USA
Phone: +1/507/284 56 43
Fax: +1/507/255 48 28
Email: miles.john@mayo.edu