Food Lipids: Chemistry, Nutrition, and Biotechnology

mals indicate that high-fat feeding induces both a decline in insulin sensitivity (216–
218) and the development of insulin resistance in a variety of tissues (219–225).
1. Level of Dietary Fat
Cellular mechanisms responsible for the decline in insulin responsiveness in association
with high-fat feeding have not been fully defined. Euglycemic, hyperinsulinemic
clamp studies in human subjects and experimental animals indicate that highfat
feeding significantly impairs insulin action (226), reduces skeletal muscle glucose
metabolism (226), and decreases the ability of insulin to suppress hepatic glucose
production (226,227). Such studies also indicate that diet-associated development of
peripheral insulin resistance may be modulated by age (228).
Reductions in insulin binding in tissues from rats fed high-fat as compared with
high-carbohydrate diets have been observed by several groups of investigators
(219,229–232). However, other investigators failed to observe significant alterations
in insulin binding in response to high-fat feeding (220,233,234). Several postreceptor
defects in insulin action (219,220,222,233–236) are observed in tissues from animals
fed high-fat diets. Specifically, reductions in insulin receptor kinase activity (234),
in the intracellular glucose transport system (222,233,235), and in the intracellular
capacity to utilize glucose for lipogenesis (220) have all been reported in association
with high-fat feeding.
2. Type of Dietary Fat
Although all diets high in fat lead to insulin resistance relative to high-carbohydrate
diets, the effect of dietary fat on insulin action is greatly influenced by the type of
fatty acid consumed [see reviews by Storlien et al. (237) and Lovejoy (238)]. High
saturated fat intakes are consistently associated with insulin resistance, whereas
monounsaturated and polyunsaturated fatty acids are less deleterious in this regard
(215,237,238). van Amelsvoort et al. (239) observed that insulin response is greater
in epididymal fat cells from rats fed diets high in polyunsaturated as compared with
saturated fats. Likewise, diets with increasing ratios of polyunsaturated to saturated
fatty acids induce alterations in the composition of adipocyte plasma membranes that
are associated in a dose-dependent manner with increases in insulin binding, insulin
receptor signaling, and glucose transporter activity (240–243). In addition, several
studies indicate that substitution of more saturated with less saturated dietary fat
sources can improve or ameliorate high-fat diet–induced impairment in insulin function
(225,239,244,245). Substitution of safflower oil (a polyunsaturated fat) for beef
tallow (a saturated fat) in a moderate-fat diet leads to an increase in the glucose
uptake response to insulin (225) and to alterations in gene expression of several
insulin signal transduction pathway intermediates (246). Specifically, the abundance
of insulin receptor substrate 1 (IRS-1) and phosphatidylinositol (PI) 3-kinase mRNA
and protein are lower in rats fed a beef tallow as compared with a safflower oil diet
(246). In contrast, insulin receptor mRNA, relative expression of insulin receptor
mRNA isoforms, and receptor protein are not influenced by dietary fat type (246).
Recent evidence demonstrating differing effects of individual fatty acids on insulinstimulated
transport/phosphorylation, but similar effects on insulin-stimulated glycogen
synthesis indicates that dietary fat type may interact with various metabolic
pathways to different degrees and through different mechanisms (247).
Copyright 2002 by Marcel Dekker, Inc. All Rights Reserved.