GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice

Takashi Nakamura, Hitomi Tanimoto, Masayuki Okamoto, Mitsuaki Takeuchi, Yoshiharu Tsubamoto, Hitoshi Noda Biological Research Group Drug Discovery Laboratories, Sanwa Kagaku Kenkyusho, Mie, JapanCorrespondence: Takashi NakamuraSanwa Kagaku Kenkyusho, Biological Research Group Drug Discovery Laborato...

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Autores principales:	Nakamura T, Tanimoto H, Okamoto M, Takeuchi M, Tsubamoto Y, Noda H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	gip，gip receptor antagonist anti-obesity lipase activity lipid metabolism Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/b29c9f85c08944e3bddec566adf6b750
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spelling	oai:doaj.org-article:b29c9f85c08944e3bddec566adf6b7502021-12-02T13:32:02ZGIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice1178-7007https://doaj.org/article/b29c9f85c08944e3bddec566adf6b7502021-03-01T00:00:00Zhttps://www.dovepress.com/gip-receptor-antagonist-skl-14959-indicated-alteration-of-the-lipids-m-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Takashi Nakamura, Hitomi Tanimoto, Masayuki Okamoto, Mitsuaki Takeuchi, Yoshiharu Tsubamoto, Hitoshi Noda Biological Research Group Drug Discovery Laboratories, Sanwa Kagaku Kenkyusho, Mie, JapanCorrespondence: Takashi NakamuraSanwa Kagaku Kenkyusho, Biological Research Group Drug Discovery Laboratories, 363 Shiosaki, Hokusei-Cho, Inabe-City, Mie, 511-0406, JapanTel +81-594-72-6221Fax +81-594-72-0071Email ta_nakamura@mb4.skk-net.comIntroduction: Glucose-dependent insulinotropic polypeptide (GIP) plays a crucial role in the regulation of lipid metabolism via lipoprotein lipase (LPL). GIP receptor antagonist, SKL-14959, suppressed the weight gain in the diet-induced obesity model. However, the mechanism is not unclear. Therefore, we aimed to give insight into the reason.Methods: Mice were divided into three groups of the low-fat diet, high-fat diets mixture with or without SKL-14959 for 151 days, and were monitored body weight and food consumption through the test. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were also performed. After that, blood, liver, muscle and adipose tissue were collected. Blood samples were measured glycosylated hemoglobin A1c (HbA1c), glucose, insulin, GIP level and plasma LPL activity. Triacylglycerol (TG) contents of liver and muscles were also measured. Moreover, a simple correlation analysis was performed.Results: SKL-14959 suppressed the body weight gain, decreased body mass index (BMI), HbA1c, and fasting glucose level, and trended to decline adipose tissues weight and TG contents compared with the vehicle, and inhibited plasma LPL activity. OGTT and ITT in the SKL-14959 group were not significantly changed relative to the vehicle. Additionally, upon treatment with SKL-14959 treatment, weight gain had weak correlation with lipase activity. Furthermore, lipase activity was associated with the fat mass and not white but red muscle TG contents and liver TG contents were not associated with lipase activity but HbA1c.In Conclusion: SKL-14959 might direct lipids metabolism to catabolism by inhibition of plasma LPL activity, resulting in the suppression of weight gain on diets-induced obesity mice.Keywords: GIP, GIP receptor antagonist, anti-obesity, lipase activity, lipid metabolismNakamura TTanimoto HOkamoto MTakeuchi MTsubamoto YNoda HDove Medical Pressarticlegip，gip receptor antagonistanti-obesitylipase activitylipid metabolismSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 1095-1105 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gip，gip receptor antagonist anti-obesity lipase activity lipid metabolism Specialties of internal medicine RC581-951
spellingShingle	gip，gip receptor antagonist anti-obesity lipase activity lipid metabolism Specialties of internal medicine RC581-951 Nakamura T Tanimoto H Okamoto M Takeuchi M Tsubamoto Y Noda H GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice
description	Takashi Nakamura, Hitomi Tanimoto, Masayuki Okamoto, Mitsuaki Takeuchi, Yoshiharu Tsubamoto, Hitoshi Noda Biological Research Group Drug Discovery Laboratories, Sanwa Kagaku Kenkyusho, Mie, JapanCorrespondence: Takashi NakamuraSanwa Kagaku Kenkyusho, Biological Research Group Drug Discovery Laboratories, 363 Shiosaki, Hokusei-Cho, Inabe-City, Mie, 511-0406, JapanTel +81-594-72-6221Fax +81-594-72-0071Email ta_nakamura@mb4.skk-net.comIntroduction: Glucose-dependent insulinotropic polypeptide (GIP) plays a crucial role in the regulation of lipid metabolism via lipoprotein lipase (LPL). GIP receptor antagonist, SKL-14959, suppressed the weight gain in the diet-induced obesity model. However, the mechanism is not unclear. Therefore, we aimed to give insight into the reason.Methods: Mice were divided into three groups of the low-fat diet, high-fat diets mixture with or without SKL-14959 for 151 days, and were monitored body weight and food consumption through the test. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were also performed. After that, blood, liver, muscle and adipose tissue were collected. Blood samples were measured glycosylated hemoglobin A1c (HbA1c), glucose, insulin, GIP level and plasma LPL activity. Triacylglycerol (TG) contents of liver and muscles were also measured. Moreover, a simple correlation analysis was performed.Results: SKL-14959 suppressed the body weight gain, decreased body mass index (BMI), HbA1c, and fasting glucose level, and trended to decline adipose tissues weight and TG contents compared with the vehicle, and inhibited plasma LPL activity. OGTT and ITT in the SKL-14959 group were not significantly changed relative to the vehicle. Additionally, upon treatment with SKL-14959 treatment, weight gain had weak correlation with lipase activity. Furthermore, lipase activity was associated with the fat mass and not white but red muscle TG contents and liver TG contents were not associated with lipase activity but HbA1c.In Conclusion: SKL-14959 might direct lipids metabolism to catabolism by inhibition of plasma LPL activity, resulting in the suppression of weight gain on diets-induced obesity mice.Keywords: GIP, GIP receptor antagonist, anti-obesity, lipase activity, lipid metabolism
format	article
author	Nakamura T Tanimoto H Okamoto M Takeuchi M Tsubamoto Y Noda H
author_facet	Nakamura T Tanimoto H Okamoto M Takeuchi M Tsubamoto Y Noda H
author_sort	Nakamura T
title	GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice
title_short	GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice
title_full	GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice
title_fullStr	GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice
title_full_unstemmed	GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice
title_sort	gip receptor antagonist, skl-14959 indicated alteration of the lipids metabolism to catabolism by the inhibition of plasma lpl activity, resulting in the suppression of weight gain on diets-induced obesity mice
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/b29c9f85c08944e3bddec566adf6b750
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GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice

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