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

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137 138 139 140 141 142 143 144 145 146 This indicates that adipocytes in iWAT from mice receiving a low amount of sucrose and a high amount of protein had a more brownish phenotype. We have previously demonstrated that a high fat diet in combination with a high protein:sucrose ratio translated into a high glucagon:insulin ratio, increased cAMP-signaling and expression of Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) leading to increased gluconeogenesis and amino acid degradation in liver (16, 17). Here we show that sucrose dose-dependently reduced expression of Ppargc1a, Pck1 (phosphoenolpyruvate carboxykinase 1, cytosolic) and Agxt (alanine-glyoxylate aminotransferase) in the liver (Fig 1F). Expression of the lipogenic gene, Fasn, was increased whereas expressions of enzymes involved in fatty acid oxidation were unchanged when the sucrose:protein ratio was increased (Fig 1F). 147 148 149 150 151 152 153 154 155 156 157 158 159 The glucose moiety of sucrose is responsible for the obesity promoting effect of sucrose. To investigate whether the obesity promoting effect of sucrose fed in combination with fish oil was depended on the glucose or fructose moiety of sucrose, we prepared diets where fish oil was combined with sucrose, glucose or fructose (Table 2). C57BL/6J mice were fed these diets adlibitum. After 7 weeks mice receiving fish oil in combination with fructose had gained less weight than mice receiving fish oil in combination with sucrose or glucose (Fig 2A). Energy intake was slightly, but not statistically significantly lower in mice fed the fructose supplemented diets and hence, energy efficiency was significantly reduced (Fig 2B). Calculation of digestibility demonstrated a minor, but not significantly reduced digestibility of protein and fat in fructose fed mice (Fig 2C). Of note, the mice receiving fructose had about 50% less white adipose tissue mass, iWAT, pWAT and eWAT, than mice receiving sucrose or glucose, combined with a tendency towards a slight decrease in the weight of the tibialis anterior muscle (Fig 2D). 8
160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 We have previously provided evidence that the different obesogenic effect of corn oil fed in combination with either protein or sucrose is related to the effect of the macronutrient composition on hormonal status (16). As sucrose and glucose, unlike fructose, stimulate insulin secretion, we measured plasma levels of glucose and insulin in the fed state. As expected, plasma glucose and insulin were lower in fructose fed mice (Fig 2E). As in mice fed a high fat diet in combination with proteins, expressions of Ppargc1a and Pck1 in the liver were increased (Fig 2F). However, unlike mice fed a high protein diet, expression of genes involved in amino acid degradation was not increased in fructose fed mice (Fig 2F). Plasma levels of 2-hydroxybutyrate, a marker for fatty acid β-oxidation, were similar in all groups, but the expression of genes involved in hepatic fatty acid oxidation was reduced in livers from fructose fed mice (Fig 2F). Hepatic expression of lipogenic genes was higher in fructose fed mice (Fig 2F). Importantly, however, excess lipid accumulation was not seen in liver or tibialis anterior muscle (Fig 3). The finding that Ucp1 expression was strongly induced in iWAT, but not iBAT in fructose fed mice, indicates that energy, as observed in protein fed mice, may be dissipated in the form of heat. Indeed, a higher expression of markers for brown adipocytes such as Ppargc1a and Cox2 (cytochrome c oxidase subunit II) suggested a higher number of brown-like adipocytes in iWAT (Fig 3C). Fructose feeding is frequently used to induce glucose intolerance in rats (26, 39) and pro-inflammatory cytokines such as CCL2 produced by both adipocytes and infiltrating macrophages are causally linked to the development of glucose intolerance (40, 41). As expression of inflammatory markers was significantly higher in mice fed fish oil in combination with glucose or sucrose than fructose (Fig 3C), a glucose tolerance test was performed in mice fed the sucrose, glucose and fructose-based diets. Of note, blood glucose levels reached higher concentrations in glucose compared to fructose fed mice and the area under the curve (AUC) was significantly higher in glucose than both sucrose and fructose fed mice (Fig 3D). 9
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: 114 115 116 117 118 119 120 121 122
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 and 50: 302 303 304 305 306 307 308 309 310
Page 51 and 52: 350 351 FIGURE LEGENDS 352 353 354
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
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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
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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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