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

was considerably less in the fish oil-fed mice than in the corn oil-fed mice (Fig.3A), but it was not
directly related to the lipogenic gene expression in their livers (Fig.3B).
Since the mice on high fat diets consumed equivalent amounts of food, the lean ones had markedly
reduced energy efficiency (Fig.3D, 4B). The following points could partly explain the differences,
1). protein-fed animals could have more brownish phenotype in inguinal WAT (iWAT) judged by
the up-regulation of Ucp1 expression, which dispenses energy as heat (Fig.3E, 4E); 2). elevated
gluconeogenesis in mice fed protein-enriched diets even in the fed state, indicated by the enhanced
glucose production during pyruvate tolerance test and hepatic gene expressions (Fig.6A and B); 3).
nitrogen metabolism was another potential contributor to the energy-wasting effect as protein
cannot be stored but must be processed immediately (Fig.6B).
In order to evaluate the role of insulin in modulating the obesogenic effects of fish oil, isocaloric
high fish oil diets with different sucrose to protein weight ratios were fed to the mice (Annex 2).
Supporting our previous findings, the fat mass development (Fig.1D), energy efficiency (Fig.1B),
inflammation levels in adipose tissues (Fig.1E) were all does-dependently correlated to sucrose
content of the diets. mRNA levels of the indicators pointing to the three energy consumption
processes, Ucp1 in the iWAT--- thermogenesis (Fig.1E); Pck1 in the live--- gluconeogenesis and
Agxt in the liver--- ureagenesis (Fig.1F), were inversely associated as earlier suggested.
By exchanging sucrose with glucose or fructose in a fish oil-supplemented diet, we further
pinpointed that the insulin stimulating agent glucose moiety in sucrose facilitated the obesitypromoting
effect of fish oil, as mice fed a fructose diet gained less WAT weights (Fig.2D) and had
lower plasma triglycerides levels (Fig.2E). However, in the same set of mice, hepatic genes related
to β-oxidation were down-regulated and the expression of lipogenic genes were increased (Fig.2F).
Our theory was further supported by including starches promote different insulin responses
(different glycemic index-GI). Although these animals did not differ in weight gain, the WAT
masses were significantly higher in high GI diet-fed mice (Fig.4A and C), and this was
accompanied by the increased expression of lipogenic genes Fasn and Scd1 (Fig.4G).
Furthermore, pharmaceutical regulators of insulin secretion were introduced to the feeding regime.
Inclusion of insulin secretagogue glybenclamide in the protein-enriched high fish oil diet did not
result in a separation of the body weight gains (Fig.5A). A tendency of fat mass differences was
observed (Fig.5B), and could be linked to observed changes in gene expression related to
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