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

was more than 3 times higher in the mice fed with high corn oil diet enriched with sucrose than with
protein. With the different diets, significant changes in body weight gains were observed both ad
libitum and pair-fed., and were due to the different degrees of adiposity. As expected, in multiple
adipose tissues, the expression of Crem (cAMP-responsive element modulator) and Pde4b (cAMPspecific
phosphodiesterase 4b) and the phosphorylation status of CREB (cAMP-responsive element
-binding protein) were differently regulated because of the diets, which revealed an altered cAMP
level. Accordingly, raised circulating PGE 2 and PGF 2 levels were detected in mice fed with a
protein supplemented diet that correlated with increased expressions of both Cox-1 and Cox-2 in
most of fat tissues.
Taken together, it was a clear demonstration of the cAMP-PKA-COX-prostaglandin axis in
regulating adipogenesis both in vitro and in vivo. The obesogenic effect of n-6 fatty acid is
dependent on the macronutrient content of the diets.
Results
As shown previously, cAMP-dependent signaling controls the obesogenic effect of n-6 PUFAs in
mice. We want to further investigate whether this phenomenon is restricted to n-6 PUFAs, or if the
beneficial effects of n-3 PUFAs can also be affected by background diets (Annex 1). To achieve
this, we prepared isocaloric diets enriched with either fish oil or corn oil (Table 1). After 9 weeks of
feeding, to our surprise, mice fed with sucrose-supplemented diets became obese regardless of the
fat sources (Fig.1 E-F). This was linked to the differential insulin to glucagon level in plasma that
we had previously identified (Fig.1 C-D), suggesting one of the determining effects background diet
has on obesity. Furthermore, the inflammation levels in the adipose tissues were correlated with
adiposity instead of dietary fat types assessed by gene expression of macrophage and inflammatory
markers (Fig.2A).
When compared to mice fed a standard chow diet, all individuals on high fat diets had impaired
glucose tolerance regardless they were fat or lean. But the separation of the HOMA index readout
implied different mechanisms underlying the observed glucose intolerance (Fig.2B). We observed
one of the recognized beneficial effects of taking fish oil in our settings. Hepatic lipid accumulation
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