Serum GSP Normal Model PSLUT-L PSLUT-H LUT MET Liver TC Normal Model PSLUT-L PSLUT-H LUT MET blood glucose 0h Normal Model PSLUT-L PSLUT-H LUT MET IL-6 Normal Model PSLUT-L PSLUT-H LUT MET AKT-1-WB Normal Model PSLUT-L PSLUT-H LUT MET 2.74571 4.27741 2.92306 2.85648 3.7347 3.48151 0.05754 0.19875 0.07538 0.02433 0.04221 0.04521 7.3 27.3 26.5 23.6 25.5 25.3 79.73612 96.65441 72.13887 69.98255 80.42145 78.46654 1.148148148 0.22962963 0.368518519 0.822222222 0.294444444 0.22037037 2.63546 4.54857 3.48581 3.26231 3.25872 3.14763 0.0755 0.17257 0.0626 0.03162 0.06755 0.04214 6.9 26.6 19.4 16.2 24.3 22.8 71.26652 90.22057 73.94803 66.50866 77.68451 81.21215 0.990740741 0.359259259 0.47962963 0.590740741 0.451851852 0.396296296 3.12476 4.26525 3.35283 3.15587 3.02546 3.57146 0.05825 0.21854 0.05364 0.04585 0.05947 0.05613 7.4 28.2 24.1 21.8 26.8 20.4 71.36655 94.42016 75.55992 73.78215 75.12542 80.46585 0.861111111 0.164814815 0.590740741 0.664814815 0.387037037 0.257407407 2.85778 4.65522 3.52528 3.24703 3.61455 3.42175 0.06198 0.26321 0.07163 0.06461 0.07521 0.06187 7.2 33 20.7 18.4 20.7 19 70.23256 84.02569 72.5771 68.41471 76.2259 79.23214 3.16246 4.24685 2.87594 3.11639 3.56875 3.27947 0.05486 0.21577 0.05825 0.05138 0.07399 0.05842 8.1 33 23.6 15.2 23.6 19.8 70.42554 84.35697 75.267 72.70373 77.12587 76.51245 3.00579 4.63548 3.32813 3.2394 3.36981 3.25543 0.06315 0.18657 0.05964 0.0488 0.06475 0.06684 6.6 31.1 24.6 19.4 26.5 17.3 76.42146 88.95478 74.01789 71.44548 73.42511 71.45465 Serum TC Normal Model PSLUT-L PSLUT-H LUT MET Liver TG Normal Model PSLUT-L PSLUT-H LUT MET blood glucose 0.5h Normal Model PSLUT-L PSLUT-H LUT MET IL-10 Normal Model PSLUT-L PSLUT-H LUT MET GLUT-2-WB Normal Model PSLUT-L PSLUT-H LUT MET 3.24725 8.15748 3.64065 2.75903 3.92547 4.89854 0.14757 0.32248 0.16266 0.13239 0.15522 0.17587 15.2 33 29.8 29.7 31.2 28.5 332.23659 215.32157 232.47758 250.71749 262.32566 241.36945 1.151933702 0.219171271 0.428342541 0.729834254 0.423756906 0.390607735 3.0874 10.06528 4.48961 3.24224 4.08582 4.42985 0.11687 0.29695 0.2177 0.15892 0.21146 0.15548 14.8 33 29.5 28.8 29.8 24.4 292.36454 186.56652 244.62062 263.8542 237.63966 242.59254 0.96961326 0.273756906 0.489502762 0.796132597 0.381767956 0.224309392 3.15872 9.35844 4.35833 4.16478 4.88755 5.87951 0.12802 0.26634 0.18964 0.14177 0.15459 0.19421 16.9 33 24.6 18.1 28.6 31.2 311.26984 214.26954 265.19545 279.26193 254.36513 266.45712 0.878453039 0.182872928 0.594033149 0.539226519 0.520607735 0.356906077 3.42419 8.11522 3.96333 4.13117 4.24561 3.71601 0.10985 0.31256 0.20628 0.18178 0.18353 0.16964 13.3 33 32.2 31.6 30.2 30.4 320.36913 217.32126 238.64087 270.77556 241.36965 255.25287 3.31189 9.37745 4.58134 3.48147 4.46845 5.6221 0.13798 0.30589 0.1738 0.16521 0.20141 0.20504 17 33 27.9 29.9 31.8 27.6 328.66451 211.26653 259.93999 286.2369 249.39695 259.45782 3.48273 8.84927 3.71638 2.97787 4.53678 5.85531 0.15158 0.34587 0.15775 0.17203 0.17562 0.16694 16.2 33 31.5 28.6 27.5 25.5 291.32557 184.36652 224.53856 243.16915 233.58945 242.74157 Serum TG Normal Model PSLUT-L PSLUT-H LUT MET Liver LDL-c Normal Model PSLUT-L PSLUT-H LUT MET blood glucose 1h Normal Model PSLUT-L PSLUT-H LUT MET acetic acid Normal Model PSLUT-L PSLUT-H LUT MET 1.27041 3.47843 2.35006 1.75263 2.12479 2.25117 0.00786 0.03555 0.00873 0.00647 0.01542 0.01101 10.8 33 25.5 29.1 27.5 26.9 31.45742 15.45664 32.37526 32.58939 31.45664 28.53511 1.19665 3.06482 2.15364 1.62355 2.06452 2.37191 0.00486 0.02185 0.01046 0.00812 0.00754 0.01858 12.3 32.4 30.2 22.8 28.8 28.3 26.05948 15.22541 27.3195 31.56504 28.44413 28.25125 1.32888 2.89582 2.22329 1.74366 1.75732 2.15716 0.00421 0.02885 0.01302 0.01133 0.01299 0.01469 9.7 33 20.3 21.6 30.4 31.6 30.34569 11.43589 30.19805 37.15264 26.84541 23.85512 1.41588 3.52575 2.14005 0.89685 2.18646 2.37365 0.00598 0.01557 0.01059 0.0086 0.01059 0.01126 12.2 28.6 26.2 17.8 25.5 24.8 30.15649 11.22121 28.53578 33.47343 32.42641 25.55541 1.05863 3.46546 1.79421 1.53339 2.01546 2.19474 0.00584 0.03416 0.01481 0.00952 0.01387 0.01766 10.3 30.5 27.1 26.8 23 21.6 32.45649 14.85428 31.81267 30.58622 35.41566 29.84541 1.31614 3.08324 2.08211 1.48461 1.89981 1.7545 0.00676 0.03151 0.01671 0.00681 0.01552 0.0167 10.8 31.2 29.8 26.1 24.8 25.4 28.46478 14.13654 26.64519 34.46811 30.15664 30.13645 Serum LDL-c Normal Model PSLUT-L PSLUT-H LUT MET Liver HDL-c Normal Model PSLUT-L PSLUT-H LUT MET blood glucose 2h Normal Model PSLUT-L PSLUT-H LUT MET propionic acid Normal Model PSLUT-L PSLUT-H LUT MET 0.35462 1.7897 0.37447 0.29703 0.42468 0.31478 0.03415 0.00716 0.01899 0.03216 0.01454 0.01202 6.2 32.2 27.4 22 29.8 20.6 17.25412 12.22565 21.40406 22.15271 21.26455 22.56442 0.1979 1.24425 0.20713 0.38769 0.29154 0.39459 0.03126 0.00857 0.0121 0.02766 0.01845 0.01368 5.3 29.4 25.1 24.7 25.5 23.7 18.12312 8.65645 18.64628 21.23492 18.03246 17.45441 0.26654 1.6526 0.31502 0.24166 0.40579 0.35157 0.02169 0.00594 0.01605 0.02534 0.02132 0.0147 6 26.5 25 19.1 22.5 20.8 18.54542 11.22565 20.10332 24.89097 19.54223 20.53654 0.39699 1.42499 0.38557 0.39502 0.3641 0.27875 0.02314 0.00683 0.01141 0.03184 0.01463 0.01214 5.6 31 16.3 23.8 20.6 22.5 17.05856 11.46541 18.89046 17.69776 21.15415 19.12115 0.23966 1.68879 0.42583 0.3501 0.32241 0.34259 0.01968 0.00619 0.00847 0.02229 0.01885 0.02116 6.6 30.9 24.5 16.4 25.9 18.5 21.26454 9.13641 21.09869 20.7336 24.24561 22.22511 0.27024 1.52699 0.3613 0.28942 0.28987 0.28875 0.02465 0.00835 0.01417 0.02992 0.02421 0.00869 4.9 29.1 17.4 12.5 18.5 17.5 15.12582 9.13257 19.11018 23.39489 19.10974 16.46512 Serum HDL-c Normal Model PSLUT-L PSLUT-H LUT MET Liver LDL-c/HDL-c Normal Model PSLUT-L PSLUT-H LUT MET AUC of OGTT Normal Model PSLUT-L PSLUT-H LUT MET isobutyric acid Normal Model PSLUT-L PSLUT-H LUT MET 3.31511 2.37782 4.29186 3.88786 3.39741 3.12487 0.230161054 4.965083799 0.45971564 0.201181592 1.060522696 0.915973378 20.625 64.175 54.35 53.575 57.5 51.05 6.32146 5.15441 5.31113 5.90248 5.22146 5.56365 3.57855 2.72426 2.8528 3.47917 3.14568 2.97598 0.15547025 2.549591599 0.86446281 0.293564714 0.408672087 1.358187135 21 62.15 54.8 47.9 55.325 50.975 6.27116 4.71213 5.24552 5.7665 5.02665 5.34561 3.38241 2.79965 4.11267 3.32529 2.98569 3.16549 0.194098663 4.856902357 0.811214953 0.447119179 0.609287054 0.999319728 20.575 61.55 46.05 40.25 55.05 54.8 5.46358 3.83357 4.62905 5.21153 4.82354 4.52321 3.24457 2.45584 3.67476 3.81332 3.35874 3.53547 0.258426966 2.279648609 0.928133216 0.270100503 0.723855092 0.927512356 20.4 61.7 49.075 45.65 49.7 49.8 6.25412 4.53216 5.00321 6.17271 5.43215 5.26455 3.69967 2.67842 3.05358 3.6566 3.48571 3.89522 0.296747967 5.518578352 1.748524203 0.427097353 0.735809019 0.834593573 21.55 63.075 52.425 47.05 52 44.2 4.85994 3.92316 4.48852 5.3299 4.58456 4.36658 3.72586 2.29875 3.21343 3.17567 2.87547 2.76126 0.274239351 3.773652695 1.179251941 0.227606952 0.641057414 1.921749137 20.3 62.225 52.95 44.975 48.225 44.875 5.36789 3.76542 4.87465 5.55764 4.46544 4.43255 Serum LDL-c/HDL-c Normal Model PSLUT-L PSLUT-H LUT MET FBG 0WK Normal Model PSLUT-L PSLUT-H LUT MET HOMA-ISI Normal Model PSLUT-L PSLUT-H LUT MET butyric acid Normal Model PSLUT-L PSLUT-H LUT MET 0.106970809 0.752664205 0.087251215 0.076399356 0.125001104 0.100733791 6.7 11.9 9.8 10.5 11.7 11.2 0.00999 0.00215 0.00423 0.00405 0.00319 0.00412 15.43565 9.13212 13.03423 18.435 13.45446 14.35665 0.055301728 0.456729534 0.072605861 0.11143175 0.092679484 0.132591617 6.5 12 10.1 13.8 13 12.7 0.00774 0.00059 0.00175 0.00453 0.00222 0.00322 12.14554 7.21324 11.30093 16.13379 12.25645 15.36659 0.078801801 0.590288072 0.076597442 0.072673361 0.135911632 0.111063374 6 11.8 11.2 11.5 12.5 10.5 0.01248 0.00299 0.00353 0.0042 0.00403 0.00297 14.62236 9.66475 13.69049 17.61819 15.62416 16.76541 0.122355197 0.580245456 0.104923859 0.103589523 0.108403747 0.078843831 6.6 10.5 12.9 10.4 10.7 10.8 0.00666 0.00135 0.00278 0.00415 0.00235 0.00116 13.05266 7.96545 12.03892 17.46949 10.32557 13.36565 0.064778751 0.630517245 0.139452708 0.095744681 0.092494786 0.087951387 6.8 12.4 12.6 10.3 10.8 9.4 0.01065 0.00276 0.00407 0.00537 0.0044 0.00432 15.08895 10.31445 13.59492 16.68624 14.36651 14.42456 0.072530906 0.664269712 0.112434377 0.091136674 0.100807868 0.104571826 6.3 10.2 11.8 12 9.6 13.8 0.00825 0.00105 0.00269 0.00371 0.00257 0.00203 13.85211 8.05263 12.71649 16.78169 11.33525 16.32566 Body weight 0WK Normal Model PSLUT-L PSLUT-H LUT MET FBG 2WK Normal Model PSLUT-L PSLUT-H LUT MET HOMA-IRI Normal Model PSLUT-L PSLUT-H LUT MET isovaleric acid Normal Model PSLUT-L PSLUT-H LUT MET 54.26 37.64 41.95 40.98 42.36 40.89 7.4 24.8 13.7 10.7 10.5 13.3 4.60215 21.53267 14.20365 13.14785 16.35416 12.85456 1.23153 0.70545 1.33792 1.89932 1.76566 1.76665 51.78 42.15 39.21 37.35 41.95 43.75 6.2 24.3 11.5 12.3 11.1 9.9 4.90326 23.83202 16.9173 14.96132 15.60215 11.359 1.46562 0.88565 1.50575 2.0605 1.85646 1.63665 48.38 39.84 43.31 42.17 39.74 39.51 6.1 25.9 14.8 8.1 12.8 8.6 3.54251 23.56251 15.25656 12.6938 13.19658 14.46443 1.17452 0.71416 1.31339 2.07059 1.86456 1.65563 52.49 41.28 40.75 40.24 41.65 40.26 7.1 28.2 12.1 10.6 11.4 9.3 5.42024 21.61026 17.94409 11.36104 15.23256 16.06584 1.42156 0.94127 1.49792 1.8542 1.62369 1.79667 47.86 42.88 39.72 42.26 38.54 41.98 6.3 26.4 12.5 12.1 14.4 8.7 3.89954 22.69665 14.5241 10.11741 13.65141 13.85564 1.14455 0.79142 1.33186 1.74533 1.54313 1.65566 49.67 40.53 39.09 41.12 40.35 38.66 6.5 27.6 10.4 9.3 12.6 13.8 5.44106 22.11254 13.151 11.8647 14.05412 15.12584 1.30236 0.95123 1.4759 2.17326 1.75544 1.75424 Body weight 2WK Normal Model PSLUT-L PSLUT-H LUT MET FBG 4WK Normal Model PSLUT-L PSLUT-H LUT MET HOMA-©µ Normal Model PSLUT-L PSLUT-H LUT MET valeric acid Normal Model PSLUT-L PSLUT-H LUT MET 54.32 35.29 39.92 43.25 42.89 38.64 7.3 27.3 26.5 23.6 25.5 25.3 68.22554 10.75154 18.18552 24.19536 17.45124 21.13565 2.72354 1.28964 2.79927 3.36779 2.54561 2.54646 50.27 41.38 42.13 40.35 41.36 41.39 6.9 26.6 19.4 16.2 24.3 22.8 63.25564 11.55622 16.66955 20.15402 22.35685 22.46584 2.40364 0.89236 2.35854 3.01208 2.73454 2.43454 51.36 37.59 40.36 43.59 42.59 41.71 7.4 28.2 24.1 21.8 26.8 20.4 65.15698 9.02546 21.03211 22.90542 22.15664 18.22458 2.91563 1.33257 2.81326 3.48602 2.42367 2.56655 49.75 39.61 43.02 41.47 41.59 37.69 7.2 33 20.7 18.4 20.7 19 63.04543 10.02456 16.33216 26.02942 15.13352 17.2259 2.17566 1.01567 2.32381 2.91277 2.57662 2.32451 52.66 40.33 42.57 45.81 43.51 39.48 8.1 33 23.6 15.2 23.6 19.8 66.55645 11.75855 18.40333 23.6848 14.35874 23.45697 2.24554 1.21365 2.38026 2.68106 2.76545 2.23666 50.28 41.06 41.68 44.06 40.29 41.83 6.6 31.1 24.6 19.4 26.5 17.3 69.68546 9.35225 19.99502 25.37771 17.26513 19.46645 2.93321 1.43001 2.83159 3.24455 2.85266 2.94562 Body weight 4WK Normal Model PSLUT-L PSLUT-H LUT MET liver tissue score Normal Model PSLUT-L PSLUT-H LUT MET AKT-1-qPCR Normal Model PSLUT-L PSLUT-H LUT MET SCFAs Normal Model PSLUT-L PSLUT-H LUT MET 58.34 39.61 38.64 45.36 42.39 35.26 1.04 5.43 2.36 2.34 3.33 2.98 0.982998455 0.602782071 0.797527048 0.899536322 0.741885626 0.816074189 74.42371 43.96391 76.26187 84.34669 75.70838 75.33295 56.27 37.53 45.88 42.89 41.87 34.59 0.85 5.87 2.07 2.06 3.07 3.31 0.806800618 0.491499227 0.86244204 0.732612056 0.686244204 0.704791345 66.46855 37.58523 66.37651 79.77283 68.35068 70.48905 61.38 35.84 42.41 45.18 43.94 39.51 1.28 5.06 2.58 1.87 3.56 3.06 0.871715611 0.408037094 0.908809892 0.825347759 0.825347759 0.658423493 73.06721 38.20657 72.74756 90.42994 71.12357 69.90246 56.84 38.22 43.66 46.38 42.36 36.44 1.37 5.28 2.96 1.73 3.11 3.53 1.047913447 0.649149923 0.741885626 0.871715611 0.649149923 0.621329212 70.11905 37.14117 68.2901 79.58037 73.53858 67.42793 59.34 37.98 40.37 43.24 44.25 36.18 0.76 5.61 2.74 1.52 2.89 3.67 1.177743432 0.547140649 0.714064915 0.982998455 0.57496136 0.760432767 77.06 40.23338 74.70692 77.76235 82.92092 74.75399 58.17 38.59 41.13 41.86 40.96 37.73 1.41 5.77 2.41 2.18 3.42 3.24 1.112828439 0.630602782 0.778979908 0.751159197 0.788253478 0.584234931 67.04617 37.46841 67.654 85.62014 69.67518 72.05964 AKT-1Ł¨scoreŁ© Normal Model PSLUT-L PSLUT-H LUT MET GLUT-2(score) Normal Model PSLUT-L PSLUT-H LUT MET GLUT-2-qPCR Normal Model PSLUT-L PSLUT-H LUT MET 187.65 113.64 141.37 163.21 136.55 129.17 186.45 62.73 146.35 166.84 130.27 128.44 1.024154589 0.502415459 0.714975845 0.821256039 0.821256039 0.792270531 196.47 127.35 155.62 154.19 130.47 133.73 172.33 68.47 139.26 154.15 124.48 121.36 1.111111111 0.570048309 0.763285024 0.879227053 0.782608696 0.734299517 183.12 106.82 150.43 168.39 124.87 138.46 179.79 54.16 143.37 159.13 119.76 134.72 1.062801932 0.618357488 0.801932367 0.946859903 0.734299517 0.685990338 176.64 132.23 137.46 160.33 120.44 124.58 189.65 50.33 132.27 174.41 126.31 139.85 0.888888889 0.695652174 0.850241546 0.985507246 0.628019324 0.647342995 180.41 121.44 145.58 170.24 134.89 144.81 192.43 6.55E+01 153.92 162.83 133.85 118.42 0.937198068 0.589371981 0.917874396 0.859903382 0.763285024 0.859903382 192.33 110.84 152.29 173.68 139.97 126.63 175.59 70.26 1.39E+02 1.60E+02 128.67 130.53 0.975845411 0.463768116 0.946859903 0.927536232 0.676328502 0.589371981 Time(h) Simulated continuous release rate in gastrointestinal tract (%) 1 5.5 9.4 14.6 2 25.8 30.1 33.2 3 53.8 59.6 64.3 4 65.2 73.1 78.9 5 73.6 83.7 86.5 6 80.9 85.5 89.6