{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:50:59Z","timestamp":1753883459388,"version":"3.41.2"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,3,28]],"date-time":"2011-03-28T00:00:00Z","timestamp":1301270400000},"content-version":"vor","delay-in-days":86,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["G0502256-77947"],"award-info":[{"award-number":["G0502256-77947"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Computational and Mathematical Methods in Medicine"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:p>The spherical anatomy of human and rat liver lobules implies that more central cells have less time to carry out their function than more peripherally located cells because blood flows past them more rapidly. This problem could be overcome if more centrilobular cells could operate at higher temperatures than periportal cells. This study presents evidence for such a temperature gradient. Firstly, we use mathematical modelling to demonstrate that temperature increases towards the centre of the lobule. Secondly, we examine the distribution of a heat\u2010generating protein and of a heat\u2010sensitive protein across the rat and human liver lobules. Double\u2010antibody staining of healthy liver from rat and human was used for visual scoring and for automated histomorphometric quantitation of the localisation of uncoupling protein\u20102 (known to generate heat) and of the transient receptor potential\u2010v4 protein (known as a highly temperature\u2010sensitive membrane protein). Both these proteins were found to be located predominantly in the centrilobular region of liver lobules. These findings support the suggestion that temperature gradients across the liver lobule may have evolved as a solution to the problem of reduced contact time between blood and cells at the centre as compared to the periphery of mammalian liver lobules.<\/jats:p>","DOI":"10.1155\/2011\/185845","type":"journal-article","created":{"date-parts":[[2011,3,28]],"date-time":"2011-03-28T19:32:36Z","timestamp":1301340756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inbuilt Mechanisms for Overcoming Functional Problems Inherent in Hepatic Microlobular Structure"],"prefix":"10.1155","volume":"2011","author":[{"given":"Robert D.","family":"Cohen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher L.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Nickols","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline","family":"Levey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara J.","family":"Boucher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen E.","family":"Greenwald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,3,28]]},"reference":[{"volume-title":"Gray\u2019s Anatomy","year":"1938","key":"e_1_2_7_1_2"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250100596"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02196"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1141"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medengphy.2005.04.020"},{"key":"e_1_2_7_6_2","first-page":"R334","article-title":"Liver heat production and temperature regulation in the anesthetized dog","volume":"237","author":"Baconnier P.","year":"1979","journal-title":"The American Journal of Physiology"},{"key":"e_1_2_7_7_2","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1172\/JCI104570","article-title":"Estimation of hepatic blood flow with indocyanine green","volume":"41","author":"Leevy C. 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