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

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To investigate whether sucrose dose-<strong>dependent</strong>ly counteracts the obesity protective effect <strong>of</strong> fish<br />

oil, we fed for 6 weeks C57BL/6J mice high fat diets containing 25 w% fat, there<strong>of</strong> 62 ± 3 g/kg n-3<br />

<strong>fatty</strong> <strong>acids</strong>, in combination with four diets <strong>of</strong> different carbohydrate:protein ratios (Table 1). All<br />

diets contained 25.12 kJ/g. Body weight gain and white adipose tissue (WAT) mass increased in<br />

parallel with the increase in the sucrose:protein ratio in the feed (Fig 1A and D). <strong>The</strong> weight <strong>of</strong><br />

interscapular brown adipose tissue (iBAT), liver and tibialis anterior muscle were not changed (not<br />

shown). Total energy intake was not statistically significantly different in the four groups, and thus,<br />

energy efficiency increased dose-<strong>dependent</strong>ly in response to the increased amount <strong>of</strong> dietary<br />

sucrose (Fig 1B). Moreover, expressions <strong>of</strong> inflammatory markers, such as Serpine1 (serine (or<br />

cysteine) peptidase inhibitor, clade E, member 1 or plasminogen activator inhibitor-1, PAI-1), Ccl2<br />

(Ccl2 chemokine (C-C motif) ligand 2, MCP1), Cd68 (CD68 antigen) and Emr1 (EGF-like module<br />

containing, mucin-like, hormone receptor-like sequence 1, F4/80) were increased in both eWAT<br />

and iWAT in the obese mice, suggesting that sucrose attenuated the anti-inflammatory effect <strong>of</strong> fish<br />

oil (Fig 1E). <strong>The</strong> expressions <strong>of</strong> Pparg (Peroxisome proliferator-activated receptor gamma), Srebf1<br />

(sterol regulatory element binding transcription factor 1) and Fasn (Fatty acid synthase) did not<br />

change significantly (Fig 1E). Mice receiving the highest amount <strong>of</strong> sucrose also lost significantly<br />

less body weight during a 24h fast (Fig 1C) than mice receiving the lowest amount <strong>of</strong> sucrose,<br />

indicative <strong>of</strong> a lower metabolic rate in high-sucrose fed mice.<br />

Energy may be lost as heat by the uncoupling activity <strong>of</strong> UCP1 (uncoupling protein 1<br />

(mitochondrial, proton carrier)) expressed in brown adipocytes, and increased expression <strong>of</strong> Ucp1<br />

can prevent diet-induced obesity. <strong>The</strong>refore, we measured Ucp1 expression in both white and<br />

brown adipose tissue depots. In iBAT Ucp1 expression was similar in all groups, but the expression<br />

<strong>of</strong> Ucp1 was significantly reduced in iWAT in mice fed the high amount <strong>of</strong> sucrose (Fig 1C and E).<br />

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