Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice

Abstract

BackgroundPolyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance.Methodology/Principal FindingsWe fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state.Conclusions/SignificanceThe background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.

High-glycemic index carbohydrates abrogate the antiobesity effect of fish oil in mice

“…Although circulating levels of inflammatory markers such as IL-6 and TNF␣ were not affected by the dietary carbohydrate source, obese mice had higher expression of macrophage markers in adipose tissue. This is in line with our earlier study where we showed that obesity rather than the n-3:n-6 PUFA ratio in both feed and adipose tissues appeared to determine the expression levels of macrophage markers in adipose tissue (40). Of note, expression of macrophage markers in the obese state was as prominent in subcutaneous iWAT as in eWAT.…”

“…We have described previously that sucrose counteracted the anti-inflammatory effect of fish oil in adipose tissue and increased obesity development in mice (40). Here, we show that the glucose moiety of sucrose was responsible for this effect, and this effect of sucrose can be mimicked by high-GI starch.…”

“…To investigate whether sucrose dose-dependently counteracted the obesity-protective effect of fish oil, male C57BL/6J mice were fed isocaloric high-fat diets with different sucrose/protein ratios (Table 1) for 6 wk. Earlier studies have demonstrated that a low sucrose/protein ratio slightly reduced feed intake in mice (40). To secure equal energy intake, all groups were pair fed.…”

“…the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice (40). 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 fed a fish oil-enriched diet in combination with protein (40).…”

Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes

“…Dietary n-3 PUFA agonists of PPAR␣ lower glucose-induced hypertriglyceridemia and improve lipoprotein patterns in normoglycemic or well-controlled diabetic individuals (45-47, 90, 130). Paradoxically, some reports in rodents (57,106) as well as human subjects (49,72,90,111) Wild-type mouse primary hepatocytes were cultured with medium containing 40 M fatty acid-free albumin and either 6 or 20 mM glucose for 1 h as described in MATERIALS AND METHODS. Culture medium and hepatocytes were then collected and cytosolic glucose level was determined as described in MATERIALS AND METHODS.…”