title: Enhanced pan-peroxisome proliferator-activated receptor gene and protein expression in adipose tissue of diet-induced obese mice treated with telmisartan.
abstract: 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 β3-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.
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Penna-de-Carvalho
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Francielle
authors.initials: F
authors.lastname: Graus-Nunes
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Júlia
authors.initials: J
authors.lastname: Rabelo-Andrade
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil souzamello.uerj@gmail.com.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Souza-Mello
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D059305:Diet, High-Fat; D015870:Gene Expression / Q000187:drug effects; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D047492:Peroxisome Proliferator-Activated Receptors; D000077333:Telmisartan