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

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Cyclooxygenases and UCP1 Figure 4. UCP1 expression is induced by forced expression of COX2 alone or in combination with COX1 in cultured cells. A. Rb 2/2 MEFs were induced to differentiate as described in experimental procedures. Differentiated adipocytes were treated with vehicle or isoproterenol (100 nM) and 9-cis-retinoic acid (1 mM) in the absence and presence of the COX1 inhibitor SC560 (50 nM) or the COX2 inhibitor NS398 (5 mM), alone or in combination, or with indomethacin (1 mM), for 24 h. Expression of UCP1 was measured by RT-qPCR. The bars represent mean 6 standard error. The experiment was performed in triplicates and repeated 2 times. B–D. Rb 2/2 MEFs were retrovirally transduced with empty vector, vector encoding COX1 or COX2, or both. The transduced cells were selected and induced to differentiate and analyzed for COX1 and COX2 expression by Western blotting (B). PGE 2 levels were measured in cell media (C). RNA was isolated on day 8 and expressions of genes were measured by RT-qPCR (D). The bars represent mean 6 standard error. Different letters indicate statistically significant difference (p,0.05). The experiments were performed in triplicates. doi:10.1371/journal.pone.0011391.g004 PLoS ONE | www.plosone.org 6 June 2010 | Volume 5 | Issue 6 | e11391
Cyclooxygenases and UCP1 Figure 5. Cold-induced UCP1 expression is attenuated in iWAT in COX2 KO mice. A B COX2 KO mice and wild-type littermates were warmacclimated at 28–30uC for 10 days and then transferred to 4–6uC for 48 h. Rectal temperature was measured before transfer and after 24 and 48 h (A). RNA was extracted and expressions of genes were measured by RT-qPCR (B). The bars represent mean 6 standard error (n = 5–6). * indicates statistical significant difference between wild-type and KO mice (p,0.05). doi:10.1371/journal.pone.0011391.g005 supplementation for 4 weeks while keeping the mice at 28–30uC. As demonstrated in Figure 7A, indomethacin supplementation led to a higher weight gain. Energy intake was slightly, but not statistically significantly lower (data not shown). However, energy intake relative to body weight gain was significantly lower in mice that received the indomethacin-supplemented high-fat diet (Figure 7A). Mice fed the diet supplemented with indomethacin also had more WAT in different depots, but not iBAT (Figure 7B). Histological analysis revealed that the adipocytes in both iWAT and iBAT appeared normal, but adipocytes in iWAT in mice fed the high-fat diet supplemented with indomethacin were slightly larger (Figure 7C and D). As expected, feeding mice a high-fat diet lead to augmented expression of UCP1 in both iBAT and iWAT in vehicle-treated mice (Figure 7E). Importantly, diet-induced UCP1 expression was prevented in iWAT, but not in iBAT in the indomethacin-treated mice (Figure 7E). Reduced expression of UCP1 in iWAT in mice fed a high-fat diet supplemented with indomethacin was accompanied with reduced expression of Cox8b. Expression of PGC1a, Dio2, Eva1, Cidea, 4E-BP1 and RIP140 was not affected by inclusion of indomethacin with the high-fat diet (Figure 7E). Collectively, these results underscore the notion that inhibition of COX activity attenuates the acquisition of ‘‘brite’’ adipocytes in white adipose depots with an accompanying increase in feed efficiency leading to accumulation of more adipose tissue. Obviously, other mechanisms may contribute to the increase in feed efficiency, but the lack of ‘‘brite’’ adipocyte recruitment seems a key player. Discussion The unique energy-dissipating ability of UCP1 makes control of its expression and activation potential targets for the development of novel drugs for the treatment of obesity and obesity-associated diseases. Here we present evidence that COX activity and COXderived PGE 2 are intimately linked to induction of UCP1 expression in iWAT, but not in iBAT. Thus, cold-induced expression of UCP1 in iWAT was repressed in mice treated with the general COX inhibitor indomethacin, and in COX2 KO PLoS ONE | www.plosone.org 7 June 2010 | Volume 5 | Issue 6 | e11391
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The obesogenic effects of polyunsat
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Table of Contents Acknowledgement .
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Abstract in Danish Polyumættede n-
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Polyunsaturated fatty acids in the
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was more than 3 times higher in the
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gluconeogenesis and ureagenesis (Fi
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high dietary PUFAs, the modulation
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In a pair of population studies, an
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18. Massiera, F. et al. Arachidonic
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54. Xu, J. et al. Polyunsaturated f
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Annexes 1. Ma T, Liaset B, Hao Q, P
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Fish Oil, Sucrose and Obesity Obesi
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Fish Oil, Sucrose and Obesity Figur
Page 27 and 28: Fish Oil, Sucrose and Obesity Table
Page 29 and 30: Fish Oil, Sucrose and Obesity Figur
Page 31 and 32: Fish Oil, Sucrose and Obesity Figur
Page 33 and 34: Fish Oil, Sucrose and Obesity 6. Ma
Page 35 and 36: Carbohydrate source and insulin sec
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Page 51 and 52: 350 351 FIGURE LEGENDS 352 353 354
Page 53 and 54: 398 399 400 401 402 403 404 subunit
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Page 57 and 58: 484 485 486 TABLE 1. Macronutrient
Page 59 and 60: Energy (kJ/g) 17.16 25.12 25.12 25.
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Page 74 and 75: Cyclooxygenases and UCP1 Although i
Page 76 and 77: Cyclooxygenases and UCP1 Figure 2.
Page 80 and 81: Cyclooxygenases and UCP1 PLoS ONE |
Page 82 and 83: Cyclooxygenases and UCP1 E synthase
Page 84 and 85: Cyclooxygenases and UCP1 29. Granne
Page 86 and 87: JBC Papers in Press. Published on J
Page 88 and 89: hydrolysate (SPH), would be protect
Page 90 and 91: was used as the liver cytosolic fra
Page 92 and 93: In order to demonstrate that bile a
Page 94 and 95: Nutritional regulation of endogenou
Page 96 and 97: in increased whole body energy expe
Page 98 and 99: 38. Kanehisa M, and Goto S. (2000)
Page 100 and 101: FOOTNOTES This work was carried out
Page 102 and 103: fed the same diets, plus the SPH-di
Page 104 and 105: Figure 2 A nmol/ min/ mg prot 2,4 1
Page 106 and 107: Figure 4 A 6 Liver Pparα B 21 Live
Page 108 and 109: Figure 7 A Plasma ALAT B Liver Ucp2
Page 110 and 111: Ruzzin et al. investigated the meta
Page 112 and 113: Ruzzin et al. CD14, and rho kinases
Page 114 and 115: Ruzzin et al. salmon oil induced a
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