The obesogenic effects of polyunsaturated fatty acids are dependent ...

20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
Introduction
A considerable number of studies has demonstrated the beneficial effects of n-3 polyunsaturated
fatty acids (PUFAs) on lipid metabolism and lipid-related disorders in humans (1-3) and increasing
the relative amount of n-3 PUFAs is presently recommended. Moreover, diets enriched with n-3
PUFAs have been demonstrated to reduce the development of insulin resistance (4-9) and to reduce
the development of diet-induced obesity in rodents (7, 10-15). We have shown that the
macronutrient composition of the diet determines the adipogenic potential of dietary corn oil in
mice (16). Moreover, we recently demonstrated that sucrose counteracts the anti-inflammatory
effect of fish oil in adipose tissue and increases obesity development in mice (17). Mice fed a fish
oil enriched diet in combination with sucrose had markedly higher feed efficiency and required less
than 50% of the calories to achieve the same weight gain as mice pair-fed a fish oil enriched diet in
combination with protein (17).
A major difference between proteins and sucrose is the ability to cause a rise in blood
glucose and stimulate insulin secretion. Insulin is a powerful anabolic hormone that stimulates
adipocyte differentiation and adipose tissue expansion (18), and activation of insulin signaling is
crucial for the development of obesity (19). Moreover, increased insulin signaling by transgenic
expression of insulin receptor substrate-1 (IRS-1) is sufficient to induce obesity (20). Thus, it is
possible that increased insulin signaling and glucose uptake in adipose tissue in the fed state in
sucrose fed mice may override the anti-inflammatory and anti-obesity effects of fish oil.
The glucose moiety of sucrose is responsible for the rise in blood insulin upon intake
of sucrose, as fructose unlike glucose, is unable to stimulate insulin secretion (21). This in part
relates to the very low levels of Slc2a5 (solute carrier family 2 (facilitated glucose transporter),
member 5, GLUT5) in pancreatic beta-cells (22). Furthermore, fructose does not stimulate the
release of gastric inhibitory peptide which stimulates insulin secretion indirectly (23, 24). Thus, the
3