Deficiency of the Purinergic Receptor 2X<sub>7</sub> Attenuates Nonalcoholic Steatohepatitis Induced by High-Fat Diet: Possible Role of the NLRP3 Inflammasome

<div>Oxidative and carbonyl stress markers. Immunohistochemistry for CML ((a); original magnification 100x) and NCF1 ((c); original magnification 100x) in liver sections from representative animals and quantification of liver CML (b) and NCF1 (d) protein content in HFD-fed WT and <i>P2x<sub>7</sub>r</i><sup>−/−</sup> mice (mean ± SD; <svg height="8.55521pt" id="M30" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 40.8856 8.55521" width="40.8856pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z" 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36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z" id="g113-81"></path></g><g transform="matrix(.013,0,0,-0.013,17.737,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path></g><g transform="matrix(.013,0,0,-0.013,29,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,35.24,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path></g><g transform="matrix(.013,0,0,-0.013,38.204,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 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364L153 550Z" id="g113-54"></path></g></svg> versus the corresponding NFD-fed mice; <svg height="12.4111pt" id="M33" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -11.7741 56.2136 12.4111" width="56.2136pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M458 122C446 142 422 163 404 170C370 149 335 141 272 139V142C272 216 281 255 311 281C280 309 275 350 272 418C335 417 370 407 404 387C422 394 447 415 458 436C447 456 424 477 402 484C370 463 335 455 272 453C276 506 282 532 312 584C297 610 275 636 253 647C232 636 208 610 194 584C223 532 230 506 234 453C171 455 136 463 102 484C84 477 60 456 48 436C60 415 84 393 102 387C136 407 171 417 234 418C231 350 226 309 195 281C226 255 231 214 234 139C171 141 136 149 102 170C84 163 60 142 48 122C60 101 84 79 102 72C136 93 171 103 234 104C230 35 224 8 195 -42C208 -69 232 -94 254 -106C274 -94 298 -69 312 -42C282 8 276 35 272 104C335 103 370 93 404 72C422 79 446 101 458 122Z" id="g50-16"></path></g><g transform="matrix(.013,0,0,-0.013,5.111,0)"><path d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z" id="g113-81"></path></g><g transform="matrix(.013,0,0,-0.013,16.769,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path></g><g transform="matrix(.013,0,0,-0.013,28.032,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,34.272,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path></g><g transform="matrix(.013,0,0,-0.013,37.236,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,43.476,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,49.716,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z" id="g113-50"></path></g></svg> versus WT mice. CML = N<i><sup>ε</sup></i>-(carboxymethyl)lysine; NCF1 = neutrophil cytosol factor 1; NFD = normal-fat diet; HFD = high-fat diet; WT = wild type; <i>Pr2x<sub>7</sub></i><sup>−/−</sup> = knockout for purinergic receptor 2X<sub>7</sub> gene.</div>

Oxidative Medicine and Cellular Longevity

fig3

Figure 3

Figure 3: Deficiency of the Purinergic Receptor 2X<sub>7</sub> Attenuates Nonalcoholic Steatohepatitis Induced by High-Fat Diet: Possible Role of the NLRP3 Inflammasome 

Figure 3 | Deficiency of the Purinergic Receptor 2X7 Attenuates Nonalcoholic Steatohepatitis Induced by High-Fat Diet: Possible Role of the NLRP3 Inflammasome 