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Volume 1, Issue 5, Pages (May 2005)

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1 Volume 1, Issue 5, Pages 331-341 (May 2005)
Molecular mechanisms associated with leptin resistance: n-3 polyunsaturated fatty acids induce alterations in the tight junction of the brain  Shinsuke Oh-I, Hiroyuki Shimizu, Tetsurou Sato, Yutaka Uehara, Shuichi Okada, Masatomo Mori  Cell Metabolism  Volume 1, Issue 5, Pages (May 2005) DOI: /j.cmet Copyright © 2005 Elsevier Inc. Terms and Conditions

2 Figure 1 Effects of the addition of 0.4% (wt/wt) saturated (stearic acid, 18:0), monounsaturated (oleic acid, 18:1), diunsaturated (linoleic acid, 18:2), or polyunsaturated (EPA, 20:5; DHA, 22:5) fatty acids in diets not containing fish oil on the anorexigenic effects of i.p. administered recombinant leptin (5.0 μg/gbw) in rats. The addition of 0.4% (wt/wt) DHA or EPA suppressed the anorexigenic effects of leptin for 3 hr (n = 7–8/group). Data represent mean ± SE. Cell Metabolism 2005 1, DOI: ( /j.cmet ) Copyright © 2005 Elsevier Inc. Terms and Conditions

3 Figure 2 A−C) Changes in 0–1 hr and 1–3 hr food intake by i.p. ([A], 0.5 μg/gbw; [B], 5.0 μg/gbw body weight) and (C) intracerebroventricular (10–1000 ng/rat) recombinant leptin administration in rats fed a diet not containing fish oil either without (Aa, Ba, Ca) or with 0.4% (wt/wt) n-3 PUFA (EPA) (Ab, Bb, Cb). D) Changes in CSF immunoreactive leptin concentration as a result of an i.p. injection of 5.0 μg/gbw recombinant leptin in rats fed a diet not containing fish oil either without or with 0.4% (wt/wt) n-3 PUFA (EPA) (n = 8–16 in each group). E) Changes in serum and CSF human immunoreactive leptin concentration and the ratio of CSF to serum human leptin concentration 60 min after an i.p. injection of 5.0 μg/gbw of recombinant human leptin in rats fed a non-fish-oil-containing diet either without or with 0.4% (wt/wt) n-3 PUFA (EPA) (n = 6 in each group). Data represent mean ± SE. Cell Metabolism 2005 1, DOI: ( /j.cmet ) Copyright © 2005 Elsevier Inc. Terms and Conditions

4 Figure 3 A) Changes in the expression of hypothalamic Ob-Ra and Ob-Rb along with serum Ob-Re concentration in rats fed a diet not containing fish oil either without or with 0.4% (wt/wt) n-3 PUFA (EPA) (n = 8 in each group). No differences in leptin receptor expression were detected between these two groups. B) Expression of hypothalamic SOCS-3, phosphorylated STAT3 (p-STAT3), and total STAT3 when measured 60 min after an i.p. injection of 5.0 μg/gbw recombinant leptin (n = 8 rats in each group). Data represent mean ± SE. Cell Metabolism 2005 1, DOI: ( /j.cmet ) Copyright © 2005 Elsevier Inc. Terms and Conditions

5 Figure 4 A−D) Changes in the expression of hypothalamic (A) claudin-5, (B) JAM-1, (C) occludin, and (D) ZO-1 in rats fed a diet not containing fish oil either without or with 0.4% (wt/wt) n-3 PUFA (EPA) (n = 8 in each group). Expression of hypothalamic occludin was markedly elevated in rats fed a diet supplemented with n-3 PUFA. E) Changes in occludin expression in eight separate regions of the brain in rats fed a diet supplemented with n-3 PUFA (n = 5 in each group). F) Chronological change of occludin expression in the hypothalamus in rats fed a diet supplemented with n-3 PUFA (n = 5 in each group). G) Changes in 0–1 hr and 1–3 hr food intake as a result of the i.p. administration of recombinant leptin without or with 0.4% (wt/wt) n-3 PUFA (EPA) at day 3 (n = 4–5 in each group). H) Changes in the expression of occludin in microvessels isolated from the hypothalamus in rats fed a diet supplemented with n-3 PUFA (n = 6 in each group). Data represent mean ± SE. Cell Metabolism 2005 1, DOI: ( /j.cmet ) Copyright © 2005 Elsevier Inc. Terms and Conditions

6 Figure 5 Changes in food intake in rats continuously infused intracerebroventricularly with 40 μg/day of antisense or 5-missense morpholino oligonucleotides directed against the rat occludin gene in animals fed a diet not containing fish oil either with or without 0.4% (wt/wt) n-3 PUFA (EPA). (A) Experimental protocol, (B) expression of hypothalamic occluding, (C) chronological changes in 0–1 hr and 1–3 hr food intake following i.p. administration of recombinant leptin (0.5–5.0 μg/gbw). Continuous intracerebroventricular infusion of antisense morpholino oligonucleotide against occludin restored leptin’s anorexigenic effects in rats fed a diet rich in n-3 PUFA (n = 4–14 in each group). Data represent mean ± SE. Cell Metabolism 2005 1, DOI: ( /j.cmet ) Copyright © 2005 Elsevier Inc. Terms and Conditions

7 Figure 6 Changes in the expression of hypothalamic occludin in rats fed diets containing 10% fat and 56% fat diet, ob/ob mice, db/db mice, Zucker fatty rats, and lean littermates. The high-fat diet increased hypothalamic occludin expression. In contrast, there were no significant changes in the expression of hypothalamic occludin when compared between lean and obese mice and rats. Data represent mean ± SE. Cell Metabolism 2005 1, DOI: ( /j.cmet ) Copyright © 2005 Elsevier Inc. Terms and Conditions


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