Teneligliptin improves metabolic abnormalities in a mouse model of postmenopausal obesity.
A decrease in serum estrogen levels in menopause is closely associated with the development of visceral obesity and the onset of type 2 diabetes in women. In the present study, we demonstrated the therapeutic effects of the novel DPP4 inhibitor, teneligliptin, on the features of postmenopausal obesity in mice. In the control group, female C57BL/6 mice were sham-operated and maintained on a standard diet. In the postmenopausal obese group, ovariectomized (OVX) mice were maintained on a high-fat diet, and were referred to as OVX-HF. In the treated group, teneligliptin at 60 mg/kg per day was administrated to OVX-HF, and were referred to as Tene. After a 12-week food challenge, the metabolic phenotypes of these mice were analyzed. Body weight, fat accumulation, and glucose intolerance were greater in OVX-HF than in control, while these abnormalities were markedly improved without alterations in calorie intake in Tene. Teneligliptin effectively ameliorated the characteristics of metabolic abnormalities associated with postmenopausal obesity. Regarding chronic inflammation in visceral adipose tissue, the numbers of F4/80(+)CD11c(+)CD206(-) M1-macrophages in flow cytometry, crown-like structure formation in immunohistochemistry, and proinflammatory cytokine expression were significantly attenuated in Tene. Hepatic steatosis was also markedly improved. Furthermore, decreased energy consumption in the dark and light phases, reduced locomotor activity in the dark phase, and lowered core body temperature in OVX-HF were ameliorated in Tene. Since obesity and reduced energy metabolism are a common physiology of menopause, teneligliptin appears to be beneficial as a treatment for type 2 diabetes in postmenopausal obesity.
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Azusa
A
Sameshima
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan twada@pha.u-toyama.ac.jp tsasaoka@pha.u-toyama.ac.jp.
Tsutomu
T
Wada
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Tetsuo
T
Ito
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Ayaka
A
Kashimura
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Kanae
K
Sawakawa
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Rika
R
Yonezawa
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Hiroshi
H
Tsuneki
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Yoko
Y
Ishii
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Masakiyo
M
Sasahara
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Shigeru
S
Saito
Departments of Obstetrics and GynecologyClinical PharmacologyPathologyUniversity of Toyama, 2630 Sugitani, Toyama 930-0194, Japan twada@pha.u-toyama.ac.jp tsasaoka@pha.u-toyama.ac.jp.
Toshiyasu
T
Sasaoka
D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000517:prevention & control; D056128:Obesity, Abdominal / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D010052:Ovariectomy; D015434:Panniculitis / Q000209:etiology / Q000517:prevention & control*; D011720:Pyrazoles / Q000627:therapeutic use*; D053778:Thiazolidines / Q000627:therapeutic use*
C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011720:Pyrazoles; D053778:Thiazolidines
adipose tissue macrophage; dpp4 inhibitor; energy expenditure; insulin resistance