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

Polyunsaturated fatty acids in the diet
Fat comes in the form of a blend of different fatty acids, namely saturated fatty acids (SFAs),
monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs). Multiple studies
suggest that the consumption of MUFAs in place of SFAs improves insulin sensitivity 14,15 . The
increased intake of n-6 PUFAs, or higher dietary n-6 to n-3 ratio, has been implicated in promoting
many diseases including obesity and diabetes 16,17 . As shown in the work of Massiera et al., in mice,
pups from mothers fed a diet enriched with n-6 linoleic acid became obese. However, this can be
prevented by inclusion of the n-3 PUFA α-linolenic acid in the diet. The authors attributed this
phenomenon to the ability of n-6 PUFAs to promote adipogenesis 18 . In line with the animal work, a
similar outcome has been observed in a human study that revealed a higher n-6/n-3 PUFA ratio in
the umbilical cord plasma was associated with a higher incidence of obesity 19 . Furthermore, work
from our group suggests that the adipogenic nature of n-6 PUFAs is dependent on the cellular
cAMP status 20 .
The possible anti-obesity mechanisms of n-3 PUFAs include, but are not limited to: 1), competition
with n-6 PUFAs in enzymatic pathways, which may dampen the adipogenic and pro-inflammatory
effects of n-6 PUFAs 21 , as one metabolic effect from obesity is chronic low-grade inflammation.
Anti-inflammatory intervention has been shown to be helpful against metabolic dysfunction 22 . 2),
up regulation of β-oxidation and mitochondrial biogenesis. In both rodent and human settings
addition of n-3 PUFAs, particularly of marine source, increased lipid oxidation 23,24 . 3), activation of
G protein-coupled receptor 120, which exerts its anti-inflammatory effects by inhibiting both Tolllike
receptor (TLR) and tissue necrosis factor- α (TNF-α) signaling pathways in the residing
macrophages in adipose tissue 25 .
Adipocyte biology
Historically, adipose tissue was seen as a static storage unit when energy is in excess and to release
energy during food deprivation in the form of fatty acids and glycerol. When energy consumption
persistently exceeds energy expenditure, expansion of adipose tissue will occur, contributed to by
both hyperplasia and hypertrophy of adipocytes and finally culminate in obesity. Recently adipose
tissue has become appreciated as an important mediator of systemic metabolism for its role of
secreting regulatory proteins 26 . The first adipokine being identified was adipsin (Factor D) from
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