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

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326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 of ca 5.4 kJ/g urea. Consistent with this notion, we have observed that fish oil combined with a high level of protein and low levels of sucrose induces hepatic expression of Ppargc1a that was accompanied by an induction of mRNAs encoding enzymes involved in catabolism of glucogenic amino. Thus, increased energy cost by increased gluconeogenesis and ureagenesis probably contribute to the reduced feed-efficiency observed by a high protein diet. In mice fed increasing amounts of protein at the expense of sucrose, we observed a dose-dependent increase in Ucp1 expression in iWAT. Others and we have recently demonstrated that cyclooxygenase-dependent induction of UCP1 expression in WAT counteracts diet-induced obesity (65, 66). The importance of UCP1 expressing brown-like adipocyte in WAT for regulation of energy expenditure is further underscored by aP2-UCP1 transgenic mice in which endogenous Ucp1 expression and respiration were reduced in iBAT, whereas UCP1 expression, respiration and total oxidative capacity were induced in WAT, and this was sufficient to account for the observed changes of total energy balance (67). Thus, UCP1-dependent uncoupled respiration in iWAT in combination with increased energy cost from gluconeogenesis may account for the reduced energyefficiency observed when sucrose levels in the diet were low. If the background diet determines the adipogenic potential of fish oil also in humans, this is of great concern, as the intake of refined sugars from sources such as soft-drinks has increased dramatically during the last several decades (68). Moreover, n-3 supplements are often taken in combination with morning meals containing high-glycemic index carbohydrates such as cereal, bread and orange juice. Thus, comprehensive studies of the interaction between dietary macronutrients and fish oil in humans seem warranted. 347 348 349 16
350 351 FIGURE LEGENDS 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 FIGURE 1. Macronutrient composition determines the obesogenic effect of fish oil. Male C57BL/6 mice (n=8) were pair-fed isocaloric high fat diets with different carbohydrate/protein ratios for 6 weeks. (A) Body weight development in pair-fed mice is shown as relative increase. (B) Energy efficiency was calculated as body weight gain divided by feed energy intake. (C) Weight reduction during 24h fasting was measured and Ucp1 (Uncoupling protein-1) and Dio2 (deiodinase, iodothyronine, type II) expressions were measured by RT-qPCR. (D-F) Adipose tissue and liver were dissected out and the weights were recorded. Expressions of Pparg (peroxisome proliferator activated receptor gamma), Srebf1 (sterol regulatory element binding transcription factor 1), Fasn (fatty acid synthase), Ucp1 (Uncoupling protein-1), Serpine1 (Plasminogen activator inhibitor-1), Ccl2 (chemokine (C-C motif) ligand 2), Cd68 (CD68 antigen) and Emr1 (EGF-like module containing, mucin-like, hormone receptor-like sequence 1 or F4/80) were measured in epididymal and inguinal white adipose tissue and expressions of Acox1 (acyl-CoA oxidase 1), Cpt1a (carnitine palmitoyltransferase 1a), Fasn (fatty acid synthase), Ppargc1a (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), Pck1 (phosphoenolpyruvate carboxykinase 1, cytosolic) and Agxt (alanine-glyoxylate aminotransferase) were measured in liver using RT-qPCR and normalized to Tbp (TATA-box binding protein). Data are presented as mean ± SEM. Different small letters denote significant differences (P
Page 1 and 2: The obesogenic effects of polyunsat
Page 3 and 4: Table of Contents Acknowledgement .
Page 5 and 6: Abstract in Danish Polyumættede n-
Page 7 and 8: Polyunsaturated fatty acids in the
Page 9 and 10: was more than 3 times higher in the
Page 11 and 12: gluconeogenesis and ureagenesis (Fi
Page 13 and 14: high dietary PUFAs, the modulation
Page 15 and 16: In a pair of population studies, an
Page 17 and 18: 18. Massiera, F. et al. Arachidonic
Page 19 and 20: 54. Xu, J. et al. Polyunsaturated f
Page 21 and 22: Annexes 1. Ma T, Liaset B, Hao Q, P
Page 23 and 24: Fish Oil, Sucrose and Obesity Obesi
Page 25 and 26: Fish Oil, Sucrose and Obesity Figur
Page 27 and 28: Fish Oil, Sucrose and Obesity Table
Page 33 and 34: Fish Oil, Sucrose and Obesity 6. Ma
Page 35 and 36: Carbohydrate source and insulin sec
Page 37 and 38: 20 21 22 23 24 25 26 27 28 29 30 31
Page 39 and 40: 68 69 70 71 72 73 74 75 76 77 78 79
Page 41 and 42: 114 115 116 117 118 119 120 121 122
Page 43 and 44: 160 161 162 163 164 165 166 167 168
Page 45 and 46: 208 209 210 211 212 213 214 215 216
Page 47 and 48: 256 257 258 259 260 261 262 263 264
Page 49: 302 303 304 305 306 307 308 309 310
Page 53 and 54: 398 399 400 401 402 403 404 subunit
Page 55 and 56: 446 447 448 449 450 451 gamma, coac
Page 57 and 58: 484 485 486 TABLE 1. Macronutrient
Page 59 and 60: Energy (kJ/g) 17.16 25.12 25.12 25.
Page 61 and 62: 561 562 563 564 565 566 567 568 569
Page 63 and 64: 635 636 637 638 639 640 641 642 643
Page 65: 711 712 713 714 715 716 717 718 719
Page 74 and 75: Cyclooxygenases and UCP1 Although i
Page 76 and 77: Cyclooxygenases and UCP1 Figure 2.
Page 78 and 79: Cyclooxygenases and UCP1 Figure 4.
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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