{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:10:43Z","timestamp":1791101443451,"version":"4.1.0"},"reference-count":28,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,7,1]]},"abstract":"<jats:p>Fatty acid\u2013binding proteins (FABPs) are cytosolic fatty acid chaperones that play a critical role in systemic regulation of lipid and glucose metabolism. In animals lacking the adipocyte\/macrophage FABP isoforms aP2 and mal1, there is strong protection against diet-induced obesity, insulin resistance, type 2 diabetes, fatty liver disease, and hypercholesterolemic atherosclerosis. On high-fat diet, FABP-deficient mice also exhibit enhanced muscle AMP-activated kinase (AMPK) and reduced liver stearoyl-CoA desaturase-1 (SCD-1) activities. Here, we performed a cross between aP2\u2212\/\u2212, mal1\u2212\/\u2212, and leptin-deficient (ob\/ob) mice to elucidate the role of leptin action on the metabolic phenotype of aP2-mal1 deficiency. The extent of obesity in the ob\/ob-aP2-mal1\u2212\/\u2212 mice was comparable with ob\/ob mice. However, despite severe obesity, ob\/ob-aP2-mal1\u2212\/\u2212 mice remained euglycemic and demonstrated improved peripheral insulin sensitivity. There was also a striking protection from liver fatty infiltration in the ob\/ob-aP2-mal1\u2212\/\u2212 mice with strong suppression of SCD-1 activity. On the other hand, the enhanced muscle AMPK activity in aP2-mal1\u2212\/\u2212 mice was lost in the ob\/ob background. These results indicated that both decreased body weight and enhanced muscle AMPK activity in aP2-mal1\u2212\/\u2212 mice are potentially leptin dependent but improved systemic insulin sensitivity and protection from liver fatty infiltration are largely unrelated to leptin action and that insulin-sensitizing effects of FABP deficiency are, at least in part, independent of its effects on total-body adiposity.<\/jats:p>","DOI":"10.2337\/db05-1496","type":"journal-article","created":{"date-parts":[[2006,6,27]],"date-time":"2006-06-27T18:39:44Z","timestamp":1151433584000},"page":"1915-1922","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":83,"title":["Regulation of Metabolic Responses by Adipocyte\/ Macrophage Fatty Acid\u2013Binding Proteins in Leptin-Deficient Mice"],"prefix":"10.2337","volume":"55","author":[{"given":"Haiming","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem Z.","family":"Gorgun","sequence":"additional","affiliation":[{"name":"Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald I.","family":"Shulman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go\u0308khan S.","family":"Hotamisligil","sequence":"additional","affiliation":[{"name":"Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031209353867000_R1","doi-asserted-by":"crossref","unstructured":"Haunerland NH, Spener F: Fatty acid-binding proteins: insights from genetic manipulations. 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