Tags

Type your tag names separated by a space and hit enter

Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model.
World J Hepatol 2019; 11(4):359-369WJ

Abstract

BACKGROUND

Obesity has been associated with hepatic overexpression of the renin-angiotensin system (RAS).

AIM

To evaluate the action of two angiotensin II (ANGII) receptor blockers (losartan or telmisartan) on the modulation of local hepatic RAS and the resulting metabolic effects in a diet-induced obesity murine model.

METHODS

Twenty C57BL/6 mice were randomly divided into two nutritional groups for 10 wk: control group (C, n = 5, 10% of energy as fat) or high-fat group (HF, n = 15, 50% of energy as fat). After treatment started, the HF group was randomly divided into three groups: untreated HF group (n = 5), HF treated with losartan (HFL, n = 5) and HF treated with telmisartan (HFT, n = 5). The treatments lasted for 5 wk, and the dose was 10 mg/kg body mass.

RESULTS

HF diet induced body mass gain (+28%, P < 0.0001), insulin resistance (+69%, P = 0.0079), high hepatic triacylglycerol (+127%, P = 0.0004), and overexpression of intrahepatic angiotensin-converting enzyme (ACE) 1/ ANGII type 1 receptor (AT1r) (+569.02% and +141.40%, respectively, P < 0.0001). The HFL and HFT groups showed higher ACE2/rMAS gene expression compared to the HF group (ACE2: +465.57%, P = 0.0002 for HFL and +345.17%, P = 0.0049 for HFT; rMAS: +711.39%, P < 0.0001 for HFL and +539.75%, P < 0.0001 for HFT), followed by reduced insulin/glucose ratio (-30% for HFL and -33% for HFT, P = 0.0181), hepatic triacylglycerol levels (-28%, P = 0.0381 for HFL; and -45%, P = 0.0010 for HFT, and Plin2 expression.

CONCLUSION

Modulation of the intrahepatic RAS, with favored involvement of the ACE2/rMAS axis over the ACE1/AT1r axis after losartan or telmisartan treatments, caused hepatic and metabolic beneficial effects as demonstrated by reduced hepatic triacylglycerol levels coupled with reduced PLIN 2 expression and improved glycemic control.

Authors+Show Affiliations

Laboratório de Morfometria, Metabolismo e Doenças Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro 20551-030, Brazil.Laboratório de Morfometria, Metabolismo e Doenças Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro 20551-030, Brazil.Laboratório de Morfometria, Metabolismo e Doenças Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro 20551-030, Brazil.Laboratório de Morfometria, Metabolismo e Doenças Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro 20551-030, Brazil.Laboratório de Morfometria, Metabolismo e Doenças Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro 20551-030, Brazil.Laboratório de Morfometria, Metabolismo e Doenças Cardiovasculares, Departamento de Anatomia, Instituto de Biologia Roberto Alcântara Gomes, Rio de Janeiro 20551-030, Brazil. souzamello.uerj@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31114640

Citation

Graus-Nunes, Francielle, et al. "Beneficial Effects of Losartan or Telmisartan On the Local Hepatic Renin-angiotensin System to Counter Obesity in an Experimental Model." World Journal of Hepatology, vol. 11, no. 4, 2019, pp. 359-369.
Graus-Nunes F, Santos FO, Marinho TS, et al. Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model. World J Hepatol. 2019;11(4):359-369.
Graus-Nunes, F., Santos, F. O., Marinho, T. S., Miranda, C. S., Barbosa-da-Silva, S., & Souza-Mello, V. (2019). Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model. World Journal of Hepatology, 11(4), pp. 359-369. doi:10.4254/wjh.v11.i4.359.
Graus-Nunes F, et al. Beneficial Effects of Losartan or Telmisartan On the Local Hepatic Renin-angiotensin System to Counter Obesity in an Experimental Model. World J Hepatol. 2019 Apr 27;11(4):359-369. PubMed PMID: 31114640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model. AU - Graus-Nunes,Francielle, AU - Santos,Felipe de Oliveira, AU - Marinho,Thatiany de Souza, AU - Miranda,Carolline Santos, AU - Barbosa-da-Silva,Sandra, AU - Souza-Mello,Vanessa, PY - 2018/12/11/received PY - 2019/02/23/revised PY - 2019/03/16/accepted PY - 2019/5/23/entrez PY - 2019/5/23/pubmed PY - 2019/5/23/medline KW - Angiotensin II type 1 receptor KW - C57BL/6 mouse KW - Liver KW - Losartan KW - Obesity KW - Telmisartan SP - 359 EP - 369 JF - World journal of hepatology JO - World J Hepatol VL - 11 IS - 4 N2 - BACKGROUND: Obesity has been associated with hepatic overexpression of the renin-angiotensin system (RAS). AIM: To evaluate the action of two angiotensin II (ANGII) receptor blockers (losartan or telmisartan) on the modulation of local hepatic RAS and the resulting metabolic effects in a diet-induced obesity murine model. METHODS: Twenty C57BL/6 mice were randomly divided into two nutritional groups for 10 wk: control group (C, n = 5, 10% of energy as fat) or high-fat group (HF, n = 15, 50% of energy as fat). After treatment started, the HF group was randomly divided into three groups: untreated HF group (n = 5), HF treated with losartan (HFL, n = 5) and HF treated with telmisartan (HFT, n = 5). The treatments lasted for 5 wk, and the dose was 10 mg/kg body mass. RESULTS: HF diet induced body mass gain (+28%, P < 0.0001), insulin resistance (+69%, P = 0.0079), high hepatic triacylglycerol (+127%, P = 0.0004), and overexpression of intrahepatic angiotensin-converting enzyme (ACE) 1/ ANGII type 1 receptor (AT1r) (+569.02% and +141.40%, respectively, P < 0.0001). The HFL and HFT groups showed higher ACE2/rMAS gene expression compared to the HF group (ACE2: +465.57%, P = 0.0002 for HFL and +345.17%, P = 0.0049 for HFT; rMAS: +711.39%, P < 0.0001 for HFL and +539.75%, P < 0.0001 for HFT), followed by reduced insulin/glucose ratio (-30% for HFL and -33% for HFT, P = 0.0181), hepatic triacylglycerol levels (-28%, P = 0.0381 for HFL; and -45%, P = 0.0010 for HFT, and Plin2 expression. CONCLUSION: Modulation of the intrahepatic RAS, with favored involvement of the ACE2/rMAS axis over the ACE1/AT1r axis after losartan or telmisartan treatments, caused hepatic and metabolic beneficial effects as demonstrated by reduced hepatic triacylglycerol levels coupled with reduced PLIN 2 expression and improved glycemic control. SN - 1948-5182 UR - https://www.unboundmedicine.com/medline/citation/31114640/Beneficial_effects_of_losartan_or_telmisartan_on_the_local_hepatic_renin-angiotensin_system_to_counter_obesity_in_an_experimental_model L2 - http://www.wjgnet.com/1948-5182/full/v11/i4/359.htm DB - PRIME DP - Unbound Medicine ER -