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Reversion of steatosis by SREBP-1c antisense oligonucleotide did not improve hepatic insulin action in diet-induced obesity mice.
Horm Metab Res 2012; 44(12):885-90HM

Abstract

The literature has associated hepatic insulin action with NAFLD. In this sense, treatments to revert steatosis and improve hepatic insulin action become important. Our group has demonstrated that inhibition of Sterol Regulatory Element Binding Proteins-1c (SREBP-1c) reverses hepatic steatosis. However, insulin signals after NAFLD reversion require better investigation. Thus, in this study, we investigated if the reversal of NAFLD by SREBP-1c inhibitor results in improvement in the hepatic insulin signal in obesity mice. After installation/achievement of diet-induced obesity and insulin resistance, Swiss mice were divided into 3 groups: i) Lean, ii) D-IHS, diet-induced hepatic steatosis [no treatment with antisense oligonucleotide (ASO)], and iii) RD-IHS, reversion of diet-induced hepatic steatosis (treated with ASO). The mice were treated with ASO SREBP-1c as previously described by our group. After ASO treatment, one set of animals was anesthetized and used for in vivo test, and another mice set was anesthetized and used for histology and Western blot analysis. Reversion of diet-induced hepatic steatosis did not change blood glucose, glucose decay constant (k(ITT)), body weight, or serum insulin levels. In addition, results showed that the protocol did not improve insulin pathway signaling, as confirmed by the absence of changes in IR, IRS1, Akt and Foxo1 phosphorylation in hepatic tissue. In parallel, no alterations were observed in proinflammatory molecules. Thus, our results suggest that the inhibition of SREBP-1c reverts steatosis, but without improving insulin hepatic resistance.

Authors+Show Affiliations

Laboratory of Exercise Biochemistry and Physiology, Programa de Pós-Graduação em Ciências da Saúde, Unidade em Ciênicas da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22932913

Citation

Vitto, M F., et al. "Reversion of Steatosis By SREBP-1c Antisense Oligonucleotide Did Not Improve Hepatic Insulin Action in Diet-induced Obesity Mice." Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, vol. 44, no. 12, 2012, pp. 885-90.
Vitto MF, Luz G, Luciano TF, et al. Reversion of steatosis by SREBP-1c antisense oligonucleotide did not improve hepatic insulin action in diet-induced obesity mice. Horm Metab Res. 2012;44(12):885-90.
Vitto, M. F., Luz, G., Luciano, T. F., Marques, S. O., Souza, D. R., Pinho, R. A., ... De Souza, C. T. (2012). Reversion of steatosis by SREBP-1c antisense oligonucleotide did not improve hepatic insulin action in diet-induced obesity mice. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, 44(12), pp. 885-90. doi:10.1055/s-0032-1321819.
Vitto MF, et al. Reversion of Steatosis By SREBP-1c Antisense Oligonucleotide Did Not Improve Hepatic Insulin Action in Diet-induced Obesity Mice. Horm Metab Res. 2012;44(12):885-90. PubMed PMID: 22932913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversion of steatosis by SREBP-1c antisense oligonucleotide did not improve hepatic insulin action in diet-induced obesity mice. AU - Vitto,M F, AU - Luz,G, AU - Luciano,T F, AU - Marques,S O, AU - Souza,D R, AU - Pinho,R A, AU - Lira,F S, AU - Cintra,D E, AU - De Souza,C T, Y1 - 2012/08/29/ PY - 2012/8/31/entrez PY - 2012/8/31/pubmed PY - 2013/4/23/medline SP - 885 EP - 90 JF - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JO - Horm. Metab. Res. VL - 44 IS - 12 N2 - The literature has associated hepatic insulin action with NAFLD. In this sense, treatments to revert steatosis and improve hepatic insulin action become important. Our group has demonstrated that inhibition of Sterol Regulatory Element Binding Proteins-1c (SREBP-1c) reverses hepatic steatosis. However, insulin signals after NAFLD reversion require better investigation. Thus, in this study, we investigated if the reversal of NAFLD by SREBP-1c inhibitor results in improvement in the hepatic insulin signal in obesity mice. After installation/achievement of diet-induced obesity and insulin resistance, Swiss mice were divided into 3 groups: i) Lean, ii) D-IHS, diet-induced hepatic steatosis [no treatment with antisense oligonucleotide (ASO)], and iii) RD-IHS, reversion of diet-induced hepatic steatosis (treated with ASO). The mice were treated with ASO SREBP-1c as previously described by our group. After ASO treatment, one set of animals was anesthetized and used for in vivo test, and another mice set was anesthetized and used for histology and Western blot analysis. Reversion of diet-induced hepatic steatosis did not change blood glucose, glucose decay constant (k(ITT)), body weight, or serum insulin levels. In addition, results showed that the protocol did not improve insulin pathway signaling, as confirmed by the absence of changes in IR, IRS1, Akt and Foxo1 phosphorylation in hepatic tissue. In parallel, no alterations were observed in proinflammatory molecules. Thus, our results suggest that the inhibition of SREBP-1c reverts steatosis, but without improving insulin hepatic resistance. SN - 1439-4286 UR - https://www.unboundmedicine.com/medline/citation/22932913/Reversion_of_steatosis_by_SREBP_1c_antisense_oligonucleotide_did_not_improve_hepatic_insulin_action_in_diet_induced_obesity_mice_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-0032-1321819 DB - PRIME DP - Unbound Medicine ER -