title: Telmisartan improves insulin resistance and modulates adipose tissue macrophage polarization in high-fat-fed mice.
abstract: Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-γ agonist, reportedly has more beneficial effects on insulin sensitivity than other angiotensin II type 1 receptor blockers. In this study, we studied the effects of telmisartan on the adipose tissue macrophage phenotype in high-fat-fed mice. Telmisartan was administered for 5 wk to high-fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in visceral adipose tissues were then examined. An insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight, and adipocyte size without affecting the amount of energy intake. Telmisartan reduced the mRNA expression of CD11c and TNF-α, M1 macrophage markers, and significantly increased the expressions of M2 markers, such as CD163, CD209, and macrophage galactose N-acetyl-galactosamine specific lectin (Mgl2), in a quantitative RT-PCR analysis. A flow cytometry analysis showed that telmisartan decreased the number of M1 macrophages in visceral adipose tissues. In conclusion, telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.
authors.affiliation: The First Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Fujisaka
authors.forename: Isao
authors.initials: I
authors.lastname: Usui
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kanatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikutani
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Agussalim
authors.initials: A
authors.lastname: Bukhari
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Hikari
authors.initials: H
authors.lastname: Suzuki
authors.forename: Satoko
authors.initials: S
authors.lastname: Senda
authors.forename: Aminuddin
authors.initials: A
authors.lastname: Aminuddin
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagai
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000098902:CD163 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001562:Benzimidazoles; D001565:Benzoates; D039521:CD11c Antigen; D015815:Cell Adhesion Molecules; D004041:Dietary Fats; D005947:Glucose; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha; D000098902:CD163 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin