Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue

Kudo, Hiroshi; Yata, Yutaka; Takahara, Taro; Kawai, Kengo; Nakayama, Yasuhiro; Kanayama, Masami; Oya, Takeshi; Morita, Seiichi; Sasahara, Masakiyo; Mann, Derek A.; Sugiyama, Toshiro

doi:10.1111/j.1478-3231.2009.02006.x

Cited by 76 publications

(53 citation statements)

References 38 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With the association of obesity and NAFLD in the metabolic syndrome, it is not surprising that increased serum and liver TNF-α expression is observed in patients 39 and rodent models of NAFLD. 40,41 Several data suggested the involvement of TNF-α and IL-6 in the metabolic syndrome and progression of NAFLD, perhaps, in part through increased mitochondrial dysfunction and 42,43 TNF-α also can contribute to the development of insulin resistance through disruption of the insulin signaling cascade at the level of insulin receptor substrate-1 pathway by Ang II. 44 Ang II-infused rats presented increased IL-6 expression in the liver with associated increase in monocyte recruitment and overall inflammation.…”

Section: -13mentioning

confidence: 99%

“…With the association of obesity and NAFLD in the metabolic syndrome, it is not surprising that increased serum and liver TNF-α expression is observed in patients 39 and rodent models of NAFLD. 40,41 Several data suggested the involvement of TNF-α and IL-6 in the metabolic syndrome and progression of NAFLD, perhaps, in part through increased mitochondrial dysfunction and 44 Ang II-infused rats presented increased IL-6 expression in the liver with associated increase in monocyte recruitment and overall inflammation. 45 A recent study showed that Ang-(1-7) was able to reduce inflammatory markers in rats with diabetic nephropathy.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Oral Formulation of Angiotensin-(1–7) Improves Lipid Metabolism and Prevents High-Fat Diet–Induced Hepatic Steatosis and Inflammation in Mice

et al. 2013

View full text Add to dashboard Cite

Abstract-Angiotensin (Ang)-(1-7) has been described as an important tool on treating and preventing metabolic disorders. In this study, we aimed to evaluate the effect of an oral formulation of Ang-(1-7) included in hydroxypropylβ-cyclodextrin (HPβCD/Ang- [1][2][3][4][5][6][7]) on hepatic function, steatosis, and on liver inflammatory markers expression in mice treated with a high-fat diet. Male FVB/N mice were divided into 4 groups and fed for 60 days, with each group receiving 1 of the following diets: standard diet+HPβCD, standard diet+Ang-(1-7)/HPβCD, high-fat diet+HPβCD, or highfat diet+Ang-[1-7]/HPβCD. Body weight, food intake, and blood parameters, such as total cholesterol, triglyceride, alaninetransaminases, and aspartate transaminases, were evaluated. Immunohistochemical analyses were performed for inflammatory markers tumor necrosis factor-α and interleukin-6. Expression of angiotensin converting enzyme, angiotensin-converting enzyme-2, interleukin-1β, tumor necrosis factor-α, interleukin-6, transforming growth factor-β, acetyl-CoA carboxylase, carbohydrate-responsive element-binding protein, peroxisome proliferator-activated receptor-γ, and sterol regulatory element-binding proteins-1c was evaluated by quantitative real-time polymerase chain reaction. The major findings of our study included reduced liver fat mass and weight, decreased plasma total cholesterol, triglyceride, and alaninetransaminase enzyme levels in the oral Ang-(1-7)-treated groups compared with the control groups. These results were accompanied by a significant reduction in tumor necrosis factor-α and interleukin-6 mRNA expression in the liver. Analyses of liver adipogenesis-related genes by quantitative real-time polymerase chain reaction showed that acetyl-CoA carboxylase, peroxisome proliferator-activated receptor-γ, and sterol regulatory element-binding proteins1c mRNA expression were significantly suppressed. In conclusion, we observed that treatment with Ang-(1-7) improved metabolism and decreased proinflammatory profile and fat deposition in liver of mice. The renin-angiotensin system (RAS) is now recognized to play an important role in the development of cardiovascular and metabolic disorders. [10][11][12][13] The RAS consists primarily of an enzymatic cascade in which angiotensinogen is converted to angiotensin (Ang) I and subsequently to Ang II by the actions of renin and Ang-converting enzyme (ACE), respectively. 14 Ang-(1-7) is formed mainly from Ang II by ACE-2 and indirectly from Ang I.14 The ACE-2/Ang-(1-7)/Mas axis has been suggested as an important counter-regulatory arm in the RAS with effects opposing those of ACE/Ang II/Ang II receptor, type 1. 13Recent studies showed an important participation of RAS in the nonalcoholic fatty liver disease (NAFLD) development and progression. The Ang II has been implicated as a major player in the altered hepatic lipid metabolism observed in NAFLD. Genetic disruption of several RAS components in rodent models results in a protection from high-fat diet (HFD)-induced obesity. [15...

show abstract

Section: -13mentioning

confidence: 99%

“…With the association of obesity and NAFLD in the metabolic syndrome, it is not surprising that increased serum and liver TNF-α expression is observed in patients 39 and rodent models of NAFLD. 40,41 Several data suggested the involvement of TNF-α and IL-6 in the metabolic syndrome and progression of NAFLD, perhaps, in part through increased mitochondrial dysfunction and 44 Ang II-infused rats presented increased IL-6 expression in the liver with associated increase in monocyte recruitment and overall inflammation. 45 A recent study showed that Ang-(1-7) was able to reduce inflammatory markers in rats with diabetic nephropathy.…”

mentioning

confidence: 99%

Oral Formulation of Angiotensin-(1–7) Improves Lipid Metabolism and Prevents High-Fat Diet–Induced Hepatic Steatosis and Inflammation in Mice

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In recent years, TEL has been reported to participate in protecting against NAFLD by regulating the expression of a variety of factors (8)(9)(10)(11). Leptin is an independence flag that could mark the progression and severity of NAFLD, and is closely related to liver lipid metabolism, steatosis, inflammation and fibrosis (12,13).…”

Section: Introductionmentioning

confidence: 99%

Effects of telmisartan on improving leptin resistance and inhibiting hepatic fibrosis in rats with non-alcoholic fatty liver disease

Zhang

Liu

Wang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. The present study aimed to investigate the impacts of telmisartan (TEL) on hepatic fibrosis, serum leptin, leptin protein in liver tissue and its mRNA expression level in rats with non-alcoholic fatty liver disease (NAFLD). Male Sprague Dawley rats were randomly divided into the control (N), model (M), polyene phosphatidylcholine (P) and TEL (T) groups. Group M and the intervention groups were given a high-fat diet for 12 weeks to induce NAFLD, followed by 4 weeks of intragastric administration of normal saline (1.0 ml/kg/day), polyene phosphatidylcholine (PPC; 123.1 mg/kg/day) and TEL (8 mg/kg/day). The liver tissue was then assessed for the NAFLD activity score and fibrosis score (FS), and serum biochemistry and leptin levels were determined. Additionally, leptin protein expression levels were examined by western blotting and the expression of leptin mRNA was investigated by reverse transcription-polymerase chain reaction. TEL significantly improved FS in rats (P<0.01) and was more effective than PPC. TEL significantly reduced the expression of serum leptin, as well as the expression levels of leptin protein and its mRNA in liver tissue (P<0.01); however, the effects of PPC were not significant (P>0.05). TEL reduced serum leptin, leptin protein and its mRNA in the liver tissue of NAFLD rats, and improved the pathological indicators of liver fibrosis.

show abstract

“…In effect, rodents with genetic deficiency of RAS components involved in angiotensin II production or intracellular signaling show reduced body fat and improvement of those metabolic parameters commonly linked with obesity (Massiéra et al 2001, Kouyama et al 2005, Yvan-Charvet et al 2009). Furthermore, inhibition of the RAS by prolonged administration of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, or a renin inhibitor to several murine models of obesity and diabetes also produces adipose tissue mass reduction, restitution of the normal adipokine profile, and recovery of glucose and lipid metabolism indicators (Mathai et al 2008, Kudo et al 2009, Santos et al 2009, Stucchi et al 2009, Weisinger et al 2009). These features associate with increased abundance of small functional adipocytes in visceral adipose tissue (Furuhashi et al 2004, Lee et al 2008 and expression of molecular markers of adipogenesis (Tomono et al 2008) in treated animals.…”

Section: Introductionmentioning

confidence: 99%

The anti-adipogenic effect of angiotensin II on human preadipose cells involves ERK1,2 activation and PPARG phosphorylation

Fuentes¹,

Acuña²,

Cifuentes³

et al. 2010

Journal of Endocrinology

View full text Add to dashboard Cite

Despite the importance of adipocyte formation for adipose tissue physiology, current knowledge about the mechanisms that regulate the recruitment of progenitor cells to undergo adipogenic differentiation is limited. A role for locally generated angiotensin II emerged from studies with human and murine cells. Preadipose cells from different human fat depots show reduced response to adipogenic stimuli when exposed to angiotensin II. This investigation sought to gain an insight into the intracellular mechanisms involved in the anti-adipogenic response of human preadipose cells from omental fat to angiotensin II. Its effect was evaluated on cells stimulated to adipogenic differentiation in vitro, by assessment of glycerol-3-phosphate dehydrogenase activity and expression of early markers of adipogenesis. Extracellular signal-regulated kinase 1,2 (ERK 1,2 ) pathway activation was inferred from the phosphorylated to total ERK 1,2 ratio determined by western blot. Exposure to angiotensin II throughout the 10-day differentiation period resulted in a reduced adipogenic response. A similar anti-adipogenic effect was observed when this hormone was present during the first 48 h of induction to differentiation. Angiotensin II treatment had no consequences on CCAAT/enhancer-binding protein b and peroxisome proliferator-activated receptor g (PPARG) induction, but increased the phosphorylated form of the key adipogenic regulator PPARG. Upon angiotensin II exposure, a raise of phosphorylated ERK 1,2 was determined, which was more prominent 8-20 h after induction of adipogenesis (when controls reached negligible values). Chemical inhibition of ERK 1,2 phosphorylation prevented angiotensin II-dependent reduction in adipogenesis. These results support the participation of the mitogen-activated protein kinase/ERK 1,2 pathway in the anti-adipogenic effect of angiotensin II on preadipose cells from human omental adipose tissue.

show abstract

Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue

Abstract: In this study, we revealed that Tel attenuated steatohepatitis progression by suppressing the macrophage infiltration into the liver. Tel also affected the reduction of adipocyte size and elevation of serum adiponectin. Tel might serve as a new therapeutic strategy for NASH.

Cited by 76 publications

References 38 publications

Oral Formulation of Angiotensin-(1–7) Improves Lipid Metabolism and Prevents High-Fat Diet–Induced Hepatic Steatosis and Inflammation in Mice

Oral Formulation of Angiotensin-(1–7) Improves Lipid Metabolism and Prevents High-Fat Diet–Induced Hepatic Steatosis and Inflammation in Mice

Effects of telmisartan on improving leptin resistance and inhibiting hepatic fibrosis in rats with non-alcoholic fatty liver disease

The anti-adipogenic effect of angiotensin II on human preadipose cells involves ERK1,2 activation and PPARG phosphorylation

Contact Info

Product

Resources

About