Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue

  title={Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue},
  author={Hao Li and Min Li and Ping Liu and Yaping Wang and Heng Zhang and Hongbin Li and Shifeng Yang and Yan Song and Yanrong Yin and Lan Gao and Si Cheng and Jiong Cai and Gang Tian},
Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level… 

Figures from this paper

Highlight article: Telmisartan improves myocardial remodeling by inhibiting leptin autocrine activity and activating PPARγ

The crosstalk between local myocardial RAAS and leptin in hypertensive LVH rats is shown and telmisartan improves myocardIAL remodeling by inhibiting local Ang II-induced leptin autocrine activity and by inhibite the leptin downstream signal STAT3 phosphorylation by activating PPAR-γ.

Inhibition of PAI-1 attenuates perirenal fat inflammation and the associated nephropathy in high-fat diet-induced obese mice.

It is found that the inhibition of PAI-1 reduced HFD-induced renal histological lesions and abated profibrotic/extracellular-matrix protein, which provides support that PAi-1 contributes to the development of inflammation in perirenal fat and correlates with theDevelopment of diabetic nephropathy in HFD -induced obesity.

Ipragliflozin Ameliorates Diabetic Nephropathy Associated with Perirenal Adipose Expansion in Mice

It is suggested that Ipra-induced PRAT expansion may play an important role in the improvement of DN in HFD-fed mice and in vitro experiments suggest that reduced PRAT-derived leptin by IpRA could inhibit GECs proliferation, possibly contributing to the suppression of DN development.

High fat diet confers vascular hyper-contractility against angiotensin II through upregulation of MLCK and CPI-17

  • Jee In Kim
  • Biology, Medicine
    The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology
  • 2017
HFD-induced hypertension is through at least in part by increased vascular contractility via increased expression and activation of contractile proteins and subsequent MLC phosphorylation induced by increased Ang II.

Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension

Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function, which could be the core pathophysiology of obesity-related hypertension.

Metabolic Syndrome-Related Kidney Injury: A Review and Update

The intervention of MetS-related renal damage is the focus of this article and includes controlling body weight, hypertension, hyperglycemia, and hyperlipidemia, requiring all components to meet the criteria.

Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases

A broad overview of novel insights linking cardiovascular derangements and CKD with a focus on metabolic disorders affecting PRAT is presented, arguing that the confluence among these pathways may open several perspectives for future pharmacological therapies against CKD and CVD possibly by modulating PRAT immunometabolism.

Ectopic Overexpression of PPARγ2 in the Heart Determines Differences in Hypertrophic Cardiomyopathy After Treatment With Different Thiazolidinediones in a Mouse Model of Diabetes

The findings show that diabetic cardiomyopathy was associated with ectopic overexpression of PPARγ2, and the full agonist rosiglitazone prevents cardiac dysfunction at the expense of compensatory hypertrophy, while the partial agonist CMHX008 shared a comparable protective effect without altering the structure of cardiomers.

Kidney Damage Caused by Obesity and Its Feasible Treatment Drugs

It is concluded that melatonin can protect the kidney damage caused by obesity by inhibiting inflammation and oxidative stress, revealing its therapeutic potential.

Cellular mechanisms underlying obesity-induced arterial stiffness.

The research over the past 5 years has underscored an important role of increased aldosterone and vascular mineralocorticoid receptor activation in driving development of cardiovascular stiffness, especially in females consuming a Western diet.



Role of adipose tissue renin-angiotensin system in metabolic and inflammatory diseases associated with obesity.

Increased adipose tissue AGT production in the obese state may be responsible in part for the metabolic and inflammatory disorders associated with obesity, and supports the notion that besides the traditional role of Ang II produced by the liver in the control of blood pressure, Ang IIproduced by the adiposes tissue may more accurately reflect the role of this hormone in the regulation of fat mass and associated disorders.

Effects of telmisartan on fat distribution in individuals with the metabolic syndrome

The results imply that telmisartan could treat both the hemodynamic and metabolic aberrations seen in patients with the metabolic syndrome, improving insulin resistance and glucose intolerance at least partly through visceral fat remodeling.

Identification of Telmisartan as a Unique Angiotensin II: Receptor Antagonist With Selective PPARγ–Modulating Activity

Abstract—The metabolic syndrome is a common precursor of cardiovascular disease and type 2 diabetes that is characterized by the clustering of insulin resistance, dyslipidemia, and increased blood

Telmisartan improves insulin resistance and modulates adipose tissue macrophage polarization in high-fat-fed mice.

Telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.

Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue.

It is suggested that ARB treatment improves insulin resistance by modification of adipose tissue thereby blunting the development of diabetes.

HIV protease inhibitors activate the adipocyte renin angiotensin system

It is reported that two frequently prescribed PI combinations could activate the adipose RAS in cultured cells, in part through a PPAR-gamma-dependant signalling pathway.

Deletion of the angiotensin type 2 receptor (AT2R) reduces adipose cell size and protects from diet-induced obesity and insulin resistance.

Data support the idea that AT2R-dependent Ang II signaling increases adipose cell mass and glucose intolerance and thus could participate to the deleterious effects of a high-fat diet.

The adipose tissue renin-angiotensin system and metabolic disorders: a review of molecular mechanisms

Because adipose RAS is overactivated in many obesity conditions, it is considered a potential candidate linking obesity to hypertension, insulin resistance and other metabolic derangements, and emerging evidence points towards a role of RAS in regulation of energy balance.

Cardioprotective Effects of Telmisartan against Heart Failure in Rats Induced By Experimental Autoimmune Myocarditis through the Modulation of Angiotensin-Converting Enzyme-2/Angiotensin 1-7/Mas Receptor Axis

Angiotensin-converting enzyme-2 (ACE-2) is a homolog of ACE that preferentially forms angiotensin-(ANG)-1-7 from angiotensin II (ANG II). We investigated the cardioprotective effects of telmisartan,