{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:00:27Z","timestamp":1791201627706,"version":"4.2.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,10,29]],"date-time":"2007-10-29T00:00:00Z","timestamp":1193616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p>Obese humans are often insulin\u2010 and leptin resistant. Since leptin can affect glucose metabolism, it is conceivable that a lack of leptin signal transduction contributes to insulin resistance. It remains unclear whether leptin affects glucose metabolism via peripheral and\/or central mechanistic routes. In the present study, we aimed: (i) to determine the relative contributions of lack of leptin signal transduction and adiposity to insulin resistance and (ii) to establish the impact of central leptin action on glucose metabolism. To address the first point, <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice were subjected to severe calorie restriction, so that their body weight became similar to that of wild\u2010type mice. Insulin sensitivity was measured in obese <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic>, lean (food restricted) <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> and lean, weight\u2010matched wild\u2010type mice. To address the second point, leptin (or vehicle) was i.c.v. infused to the lateral cerebral ventricle of <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice and insulin sensitivity was determined. Hyperinsulinaemic euglyceamic clamps were used to quantify insulin sensitivity. Food restriction barely affected body composition, although it profoundly curtailed body weight. Insulin suppressed hepatic glucose production (HGP) to a greater extent in lean <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> than in obese <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice, but its impact remained considerably less than in wild\u2010type mice (% suppression: 11.8\u2003\u00b1\u20038.9 versus 1.3\u2003\u00b1\u20031.1 versus 56.6\u2003\u00b1 13.0%\/nmol, for lean, obese <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> and wild\u2010type mice, respectively; P\u2003&lt;\u20030.05). The insulin\u2010mediated glucose disposal (GD) of lean <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice was also in between that of obese <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> and wild\u2010type mice (37.5\u2003\u00b1\u200321.4 versus 25.1\u2003\u00b1\u200314.6 versus 59.6\u2003\u00b1\u200317.3\u2003\u03bcmol\/min\/kg\/nmol of insulin, respectively; P\u2003&lt;\u20030.05 wild\u2010type versus obese <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice). Leptin infusion acutely enhanced both hepatic insulin sensitivity (insulin\u2010induced inhibition of HGP) and insulin\u2010mediated GD (9.1\u2003\u00b1\u20032.4 versus 5.0\u2003\u00b1\u20032.7%\/nmol of insulin, and 25.6\u2003\u00b1\u20035.6 versus 13.6\u2003\u00b1\u20034.8\u2003\u03bcmol\/min\/kg\/nmol of insulin, respectively; P\u2003&lt;\u20030.05 for both comparisons) in <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice. Both a lack of leptin signals and adiposity may contribute to insulin resistance in obese individuals. Diminution of central leptin signalling can critically affect glucose metabolism in these individuals.<\/jats:p>","DOI":"10.1111\/j.1365-2826.2007.01626.x","type":"journal-article","created":{"date-parts":[[2010,8,10]],"date-time":"2010-08-10T21:57:36Z","timestamp":1281477456000},"page":"120-127","source":"Crossref","is-referenced-by-count":34,"title":["Leptin Deficiency <i>Per Se<\/i> Dictates Body Composition and Insulin Action in <i>ob<\/i>\/<i>ob<\/i> Mice"],"prefix":"10.1111","volume":"20","author":[{"given":"A. M.","family":"Van Den Hoek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Teusink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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