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HFF animals consumed more ( P &lt; 0.05) calories from fat (31.9 \u00b1 1.2 vs. 2.4 \u00b1 0.2 kcal\/day) and had significantly greater final body weights (280 \u00b1 10 vs. 250 \u00b1 5 g) and total visceral fat (24 \u00b1 3 vs. 10 \u00b1 1 g). Fasting plasma insulin was 2.3-fold elevated in HFF rats. Glucose tolerance (58%) and whole body insulin sensitivity (75%) were markedly impaired in HFF animals. In HFF plantaris muscle, in vivo insulin receptor \u03b2-subunit (IR-\u03b2) and insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and phosphorylation of Akt Ser473 and glycogen synthase kinase-3\u03b2 (GSK-3\u03b2) Ser9, relative to circulating insulin levels, were decreased by 40\u201359%. In vitro insulin-stimulated glucose transport in HFF soleus was decreased by 54%, as were IRS-1 tyrosine phosphorylation (26%) and phosphorylation of Akt Ser473 (38%) and GSK-3\u03b2 Ser9 (25%), the latter indicative of GSK-3 overactivity. GSK-3 inhibition in HFF soleus using CT98014 increased insulin-stimulated glucose transport (28%), IRS-1 tyrosine phosphorylation (28%) and phosphorylation of Akt Ser473 (38%) and GSK-3\u03b2 Ser9 (48%). In summary, the female lean Zucker rat fed a high-fat diet represents an isocaloric model of nutritionally-induced insulin resistance associated with moderate visceral fat gain, hyperinsulinemia, and impairments of skeletal muscle insulin-signaling functionality, including GSK-3\u03b2 overactivity.<\/jats:p>","DOI":"10.1152\/ajpregu.00178.2008","type":"journal-article","created":{"date-parts":[[2008,4,3]],"date-time":"2008-04-03T01:55:39Z","timestamp":1207187739000},"page":"R1813-R1821","source":"Crossref","is-referenced-by-count":14,"title":["The high-fat-fed lean Zucker rat: a spontaneous isocaloric model of fat-induced insulin resistance associated with muscle GSK-3 overactivity"],"prefix":"10.1152","volume":"294","author":[{"given":"Erik J.","family":"Henriksen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary 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