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Enhanced pan‐peroxisome proliferator‐activated receptor gene and protein expression in adipose tissue of diet‐induced obese mice treated with telmisartan
Author(s) -
PennadeCarvalho Aline,
GrausNunes Francielle,
RabeloAndrade Júlia,
MandarimdeLacerda Carlos Alberto,
SouzaMello Vanessa
Publication year - 2014
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2014.081596
Subject(s) - endocrinology , medicine , telmisartan , thermogenesis , adipokine , insulin resistance , brown adipose tissue , thermogenin , adipose tissue , white adipose tissue , peroxisome proliferator activated receptor , receptor , biology , insulin , blood pressure
New FindingsWhat is the central question of this study? Telmisartan, an antihypertensive, has beneficial side‐effects through its peroxisome proliferator‐activated receptor (PPAR) β/δ agonism in white adipose tissue, besides its well‐known property of partial PPARγ agonism. Here, we investigated a potential pan‐PPAR role of this drug in the white and brown adipose tissues.What is the main finding and its importance? Telmisartan enhanced pan‐PPAR gene and protein expression in adipose tissue (white and brown) in obese mice, with downstream effects that resulted in the management of insulin resistance, anti‐inflammatory adipokine profile and thermogenesis induction. These findings are relevant and should be explored as new targets for controlling obesity and comorbidities through pan‐PPAR‐related effects.Telmisartan has previously been used to target obesity, showing peroxisome proliferator‐activated receptor (PPAR) β/δ‐related effects in white adipose tissue (WAT). We sought to evaluate whether telmisartan enhances gene and protein expression of all PPAR isoforms in WAT and brown adipose tissue (BAT), as well as their downstream effects upon insulin resistance, adipokine profile and adaptive thermogenesis. Male C57BL/6 mice were fed standard chow (SC; 10% lipids) or high‐fat diet (HF; 50% lipids) for 10 weeks. Animals were then randomly allocated into the following four groups: SC, SC‐T, HF and HF‐T. Telmisartan [10 mg (kg diet) −1 ] was administered for 4 weeks in the diet. Animals in the HF group were overweight and exhibited hypertension, insulin resistance, decreased energy expenditure, a pro‐inflammatory adipokine profile and abnormal fat pad mass distribution. Animals in the HF group showed decreased expression of PPARα, β/δ and γ in WAT and BAT, resulting in impaired glucose uptake and insufficient thermogenesis. Due to the improvement in the adipokine profile and enhanced insulin sensitivity with adequate insulin‐stimulated glucose uptake after treatment with telmisartan, the activation of all PPAR isoforms in WAT was beneficial. In BAT, telmisartan induced sustained sympathetic activation, because the β 3 ‐adrenergic receptor was induced by PPARβ/δ, while uncoupling protein 1 was induced by PPARα to promote thermogenesis. Telmisartan exerted anti‐obesity effects through higher pan‐PPAR gene and protein expression. Upon PPARα, β/δ and γ (pan‐PPAR) agonism in adipose tissue of obese mice, telmisartan ameliorates inflammation and insulin resistance, as well as inducing non‐shivering thermogenesis. Our results point to new therapeutic targets for the control of obesity and comorbidities through pan‐PPAR‐related effects.