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. 2011;6(6):e21647.
doi: 10.1371/journal.pone.0021647. Epub 2011 Jun 28.

Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

Tao Ma  1 , Bjørn Liaset, Qin Hao, Rasmus Koefoed Petersen, Even Fjære, Ha Thi Ngo, Haldis Haukås Lillefosse, Stine Ringholm, Si Brask Sonne, Jonas Thue Treebak, Henriette Pilegaard, Livar Frøyland, Karsten Kristiansen, Lise Madsen
Affiliations

Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

Tao Ma et al. PLoS One. 2011.

Abstract

Background: Polyunsaturated 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 findings: We 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/significance: The 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Sucrose counteracts the obesity-reducing effect of fish oil in ad libitum fed mice.
Male C57BL/6 mice (n = 8) were fed isocaloric high fish oil or high corn oil diets with different carbohydrate and protein contents ad libitum for 9 weeks. A: Body weight development of ad libitium fed mice. (B) Prior to termination the mice were photographed. C–D: Insulin and glucagon levels were measured in plasma in the fed state. E–G: The weights of epididymal and inguinal white adipose tissues were recorded and sections were stained with hematoxylin and eosin. Data are presented as means ± SEM. Different small letters denote significant differences between the groups (P<0.05).
Figure 2
Figure 2. A high fat diet impairs glucose tolerance independent of macronutrient composition and obesity.
A: Expressions of adipogenic and inflammatory marker genes (Pparg (peroxisome proliferator activated receptor γ), Adipoq (adiponectin), Serpine1 (Plasminogen activator inhibitor-1), Ccl2 (chemokine (C-C motif) ligand 2), Emr1 (EGF-like module containing, mucin-like, hormone receptor-like sequence 1 or F4/80) and Cd68 (CD68 antigen)) were measured in epididymal and inguinal white adipose tissue using RT-qPCR (n = 8). B: Intraperitoneal glucose tolerance test was performed in a separate set of mice (n = 10). Fasting glucose and insulin levels were measured to calculate HOMA-IR. Data are presented as means ± SEM. Different small letters denote significant differences between the groups, in 2A within the same tissue (P<0.05).
Figure 3
Figure 3. Fish oil prevents diet-induced accumulation of fat in the liver.
A: Total lipids were extracted from liver and separated using HPTLC. B: Expressions of lipogenic genes (Srebf1 (sterol regulatory element binding transcription factor 1) and Acaca (acetyl-Coenzyme A carboxylase alpha) were measured by RT-qPCR. C: Plasma triacylglycerol and β-hydroxybutyrate were measured in the fed state. D: Energy efficiency was calculated based on energy intake and body weight gain. E: Expression levels of brown adipose tissue marker genes (Ucp1 (Uncoupling protein-1), Ppargc1a (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), Cpt1b (carnitine palmitoyltransferase-1b) and Dio2 (deiodinase, iodothyronine, type II) were measured in white adipose tissues using RT-qPCR. Data are presented as means ± SEM (n = 8). Different small letters denote significant differences between the groups, in 3E within the same tissue (P<0.05).
Figure 4
Figure 4. Sucrose counteracts the obesity-reducing effect of fish oil in pair-fed mice.
Male C57BL/6 mice (n = 8) were pair-fed isocaloric high fish oil diets with different carbohydrate and protein contents for 8 weeks. A: Body weight development was followed throughout the feeding regime. B: Energy efficiency was calculated based on energy intake, weight gain and apparent digestibility. C: The weights of different adipose tissue depots were recorded. D: Insulin and glucagon levels were measured in plasma in the fed state. E: Inflammation and adipocyte marker genes (Pparg (peroxisome proliferator-activated receptor γ), Adipoq (adiponectin), Serpine1 (Plasminogen activator inhibitor-1), Ccl2 (chemokine (C-C motif) ligand 2), Emr1 (EGF-like module containing, mucin-like, hormone receptor-like sequence 1 or F4/80) and Cd68 (CD68 antigen) and F: thermogenesis-related genes (Ucp1 (Uncoupling protein-1) and cyt COXII, (cytochrome c oxidase, subunit II) were measured by RT-qPCR in adipose tissues. Data are presented as means ± SEM. Different small letters denote significant differences between the groups, in 4E within the same tissue (P<0.05).
Figure 5
Figure 5. Metabolic parameters in mice fed fish oil in combination with sucrose or protein.
A. Intraperitoneal glucose tolerance test was performed in mice pair fed fish oil enriched diets (n = 10). B. β-hydroxybutyrate, triacylglycerol, glycerol and free fatty acids were measured in pair-fed mice in both fasted and fed state (n = 10). C. Oxygen consumption, carbon dioxide and respiratory exchange ratio were measured during a 24-h period with indirect calorimetry (n = 8). Data are presented as means ± SEM. Different small letters denote significant differences between the groups, in 5B between fasted or fed state (P<0.05).
Figure 6
Figure 6. Gluconeogenesis is increased in fed state when animals are fed fish oil supplemented with protein.
A. Pyruvate tolerance tests were performed on mice in 16 h fasted (n = 7) and fed states (n = 10). B. Hepatic gene expression (Crem (cAMP responsive element modulator), Pde4c (phosphodiesterase 4C, cAMP specific), Ppargc1a (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), Pck1 (phosphoenolpyruvate carboxykinase 1, cytosolic), Gpt (glutamic pyruvic transaminase), Got1 (glutamate oxaloacetate transaminase 1), Agxt (alanine-glyoxylate aminotransferase), Cps1 (carbamoyl-phosphate synthetase 1), Acox1 (acyl-CoA oxidase 1), Cpt1a (carnitine palmitoyltransferase 1a), Cpt2 (carnitine palmitoyltransferase 2), Hmgcs2 (3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2), Srebf1 (sterol regulatory element binding transcription factor 1), scd1 (stearoyl-Coenzyme A desaturase 1), Acaca (acetyl-Coenzyme A carboxylase alpha), Fasn (fatty acid synthase), was measured using RT-qPCR (n = 8). Data are presented as means ± SEM. Different small letters denote significant differences between the different groups (P<0.05).
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