Kabir_2005_Am.J.Physiol.Endocrinol.Metab_288_E454

Reference

Title : Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance - Kabir_2005_Am.J.Physiol.Endocrinol.Metab_288_E454
Author(s) : Kabir M , Catalano KJ , Ananthnarayan S , Kim SP , Van Citters GW , Dea MK , Bergman RN
Ref : American Journal of Physiology Endocrinol Metab , 288 :E454 , 2005
Abstract : The mechanism by which increased central adiposity causes hepatic insulin resistance is unclear. The "portal hypothesis" implicates increased lipolytic activity in the visceral fat and therefore increased delivery of free fatty acids (FFA) to the liver, ultimately leading to liver insulin resistance. To test the portal hypothesis at the transcriptional level, we studied expression of several genes involved in glucose and lipid metabolism in the fat-fed dog model with visceral adiposity vs. controls (n = 6). Tissue samples were obtained from dogs after 12 wk of either moderate fat (42% calories from fat; n = 6) or control diet (35% calories from fat). Northern blot analysis revealed an increase in the ratio of visceral to subcutaneous (v/s ratio) mRNA expression of both lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor-gamma (PPARgamma). In addition, the ratio for sterol regulatory element-binding transcription factor-1 (SREBP-1) tended to be higher in fat-fed dogs, suggesting enhanced lipid accumulation in the visceral fat depot. The v/s ratio of hormone-sensitive lipase (HSL) increased significantly, implicating a higher rate of lipolysis in visceral adipose despite hyperinsulinemia in obese dogs. In fat-fed dogs, liver SREBP-1 expression was increased significantly, with a tendency for increased fatty acid-binding protein (FABP) expression. In addition, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK) increased significantly, consistent with enhanced gluconeogenesis. Liver triglyceride content was elevated 45% in fat-fed animals vs. controls. Moreover, insulin receptor binding was 50% lower in fat-fed dogs. Increased gene expression promoting lipid accumulation and lipolysis in visceral fat, as well as elevated rate-limiting gluconeogenic enzyme expression in the liver, is consistent with the portal theory. Further studies will need to be performed to determine whether FFA are involved directly in this pathway and whether other signals (either humoral and/or neural) may contribute to the development of hepatic insulin resistance observed with visceral obesity.
ESTHER : Kabir_2005_Am.J.Physiol.Endocrinol.Metab_288_E454
PubMedSearch : Kabir_2005_Am.J.Physiol.Endocrinol.Metab_288_E454
PubMedID: 15522994

Related information

Gene_locus_frgt canfa-hslipcanfa-lipli

Citations formats

Kabir M, Catalano KJ, Ananthnarayan S, Kim SP, Van Citters GW, Dea MK, Bergman RN (2005)
Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance
American Journal of Physiology Endocrinol Metab 288 :E454

Kabir M, Catalano KJ, Ananthnarayan S, Kim SP, Van Citters GW, Dea MK, Bergman RN (2005)
American Journal of Physiology Endocrinol Metab 288 :E454

Array
(
    [id] => 9340
    [paper] => Kabir_2005_Am.J.Physiol.Endocrinol.Metab_288_E454
    [author] => Kabir M || Catalano KJ || Ananthnarayan S || Kim SP || Van Citters GW || Dea MK || Bergman RN
    [year] => 2005
    [title] => Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance
    [journal] => American Journal of Physiology Endocrinol Metab
    [volume] => 288
    [page] => E454
    [medline] => 15522994
    [abstract] => Kabir_2005_Am.J.Physiol.Endocrinol.Metab_288_E454
    [kin_reference] => 
    [mutation] => 
    [kinetic_parameter] => 
    [inhibitor] => 
    [kin_value] => 
    [substrate] => 
    [gene_locus] => Array
        (
        )

    [family] => 
    [interact_gene_locus] => 
    [xenobiotic_sensitivity] => 
    [news] => 
    [likid_reference] => 
    [lip_reference] => 
    [gene_locus_frgt] => canfa-hslip || canfa-lipli
    [structure] => 
    [comment] => 
    [chemical] => 
    [arpigny_jaeger] => 
    [reactivator] => 
    [disease] => 
    [enzyme] => 
    [risk_factor] => 
    [tissue] => 
    [sub_tissue] => 
    [activity] => 
    [specific_activity] => 
    [disease_by_interaction] => 
    [abstract_text] => Array
        (
            [id] => 91870
            [longtext] => Kabir_2005_Am.J.Physiol.Endocrinol.Metab_288_E454
            [content] => The mechanism by which increased central adiposity causes hepatic insulin resistance is unclear. The "portal hypothesis" implicates increased lipolytic activity in the visceral fat and therefore increased delivery of free fatty acids (FFA) to the liver, ultimately leading to liver insulin resistance. To test the portal hypothesis at the transcriptional level, we studied expression of several genes involved in glucose and lipid metabolism in the fat-fed dog model with visceral adiposity vs. controls (n = 6). Tissue samples were obtained from dogs after 12 wk of either moderate fat (42% calories from fat; n = 6) or control diet (35% calories from fat). Northern blot analysis revealed an increase in the ratio of visceral to subcutaneous (v/s ratio) mRNA expression of both lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor-gamma (PPARgamma). In addition, the ratio for sterol regulatory element-binding transcription factor-1 (SREBP-1) tended to be higher in fat-fed dogs, suggesting enhanced lipid accumulation in the visceral fat depot. The v/s ratio of hormone-sensitive lipase (HSL) increased significantly, implicating a higher rate of lipolysis in visceral adipose despite hyperinsulinemia in obese dogs. In fat-fed dogs, liver SREBP-1 expression was increased significantly, with a tendency for increased fatty acid-binding protein (FABP) expression. In addition, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK) increased significantly, consistent with enhanced gluconeogenesis. Liver triglyceride content was elevated 45% in fat-fed animals vs. controls. Moreover, insulin receptor binding was 50% lower in fat-fed dogs. Increased gene expression promoting lipid accumulation and lipolysis in visceral fat, as well as elevated rate-limiting gluconeogenic enzyme expression in the liver, is consistent with the portal theory. Further studies will need to be performed to determine whether FFA are involved directly in this pathway and whether other signals (either humoral and/or neural) may contribute to the development of hepatic insulin resistance observed with visceral obesity.
        )

)