CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis

GNPDA2 has been associated with human obesity and type-2 diabetes by using a GWAS approach. GNPDA2 is an enzyme involved in the hexosamine biosynthesis pathway, which is known to be important for nutrient sensing in various organism. Its counter enzyme, GFAT, has previously been shown to be importan...

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Autores principales:	Ruth Gutierrez-Aguilar, Bernadette E. Grayson, Dong-Hoon Kim, Suma Yalamanchili, Mario L. Calcagno, Stephen C. Woods, Randy J. Seeley
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glucosamine-6-phosphate deaminase 2 glutamine-fructose-6-phosphate aminotransferase (GFAT) glucose homeostasis third ventricle of the hypothalamus appetite control Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/929cf6355a8040a892243288d86fea76
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spelling	oai:doaj.org-article:929cf6355a8040a892243288d86fea762021-12-01T13:16:52ZCNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis2296-861X10.3389/fnut.2021.787470https://doaj.org/article/929cf6355a8040a892243288d86fea762021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnut.2021.787470/fullhttps://doaj.org/toc/2296-861XGNPDA2 has been associated with human obesity and type-2 diabetes by using a GWAS approach. GNPDA2 is an enzyme involved in the hexosamine biosynthesis pathway, which is known to be important for nutrient sensing in various organism. Its counter enzyme, GFAT, has previously been shown to be important to the development of insulin resistance in diabetes. The implication of GNPDA2 and GFAT in metabolism is scarce and the effect of both enzymes over appetite and glucose homeostasis is unknown.Aim: Identify the role of GNPDA2 and GFAT in nutrient sensing circuits of the CNS that are important for the regulation of both appetite and glucose homeostasis.Methods: Using Long Evans rats, we administered either a GNPDA2 or GFAT antagonist or vehicle in i3vt.Key Findings:GNPDA2 is highly expressed in hypothalamus and adipose tissue, followed by muscle and liver. GNPDA2 is expressed in different hypothalamic nuclei (ARC, DMH, LHA, PVN). GNPDA2 is downregulated in hypothalamus under diet-induced obesity (as previously described), but GFAT expression does not change. Moreover, i3vt infusion of GNPDA2 or GFAT inhibitor resulted in increased c-Fos in areas related to appetite and glucose homeostasis control as PVN and DMH and to a lesser extent in the LHA and ARC. Central inhibition of GNPDA2 does not alter either acute food intake or body weight; however, GFAT inhibition diminished appetite and body weight due to visceral illness. In addition, central administration of the GNPDA2 antagonist, prior to an intraperitoneal glucose tolerance test, resulted in glucose intolerance in comparison to vehicle without altering insulin levels.Significance: These results suggest that central GNPDA2 does not control appetite, but regulates glucose homeostasis.Ruth Gutierrez-AguilarRuth Gutierrez-AguilarBernadette E. GraysonDong-Hoon KimSuma YalamanchiliMario L. CalcagnoStephen C. WoodsRandy J. SeeleyFrontiers Media S.A.articleglucosamine-6-phosphate deaminase 2glutamine-fructose-6-phosphate aminotransferase (GFAT)glucose homeostasisthird ventricle of the hypothalamusappetite controlNutrition. Foods and food supplyTX341-641ENFrontiers in Nutrition, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glucosamine-6-phosphate deaminase 2 glutamine-fructose-6-phosphate aminotransferase (GFAT) glucose homeostasis third ventricle of the hypothalamus appetite control Nutrition. Foods and food supply TX341-641
spellingShingle	glucosamine-6-phosphate deaminase 2 glutamine-fructose-6-phosphate aminotransferase (GFAT) glucose homeostasis third ventricle of the hypothalamus appetite control Nutrition. Foods and food supply TX341-641 Ruth Gutierrez-Aguilar Ruth Gutierrez-Aguilar Bernadette E. Grayson Dong-Hoon Kim Suma Yalamanchili Mario L. Calcagno Stephen C. Woods Randy J. Seeley CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis
description	GNPDA2 has been associated with human obesity and type-2 diabetes by using a GWAS approach. GNPDA2 is an enzyme involved in the hexosamine biosynthesis pathway, which is known to be important for nutrient sensing in various organism. Its counter enzyme, GFAT, has previously been shown to be important to the development of insulin resistance in diabetes. The implication of GNPDA2 and GFAT in metabolism is scarce and the effect of both enzymes over appetite and glucose homeostasis is unknown.Aim: Identify the role of GNPDA2 and GFAT in nutrient sensing circuits of the CNS that are important for the regulation of both appetite and glucose homeostasis.Methods: Using Long Evans rats, we administered either a GNPDA2 or GFAT antagonist or vehicle in i3vt.Key Findings:GNPDA2 is highly expressed in hypothalamus and adipose tissue, followed by muscle and liver. GNPDA2 is expressed in different hypothalamic nuclei (ARC, DMH, LHA, PVN). GNPDA2 is downregulated in hypothalamus under diet-induced obesity (as previously described), but GFAT expression does not change. Moreover, i3vt infusion of GNPDA2 or GFAT inhibitor resulted in increased c-Fos in areas related to appetite and glucose homeostasis control as PVN and DMH and to a lesser extent in the LHA and ARC. Central inhibition of GNPDA2 does not alter either acute food intake or body weight; however, GFAT inhibition diminished appetite and body weight due to visceral illness. In addition, central administration of the GNPDA2 antagonist, prior to an intraperitoneal glucose tolerance test, resulted in glucose intolerance in comparison to vehicle without altering insulin levels.Significance: These results suggest that central GNPDA2 does not control appetite, but regulates glucose homeostasis.
format	article
author	Ruth Gutierrez-Aguilar Ruth Gutierrez-Aguilar Bernadette E. Grayson Dong-Hoon Kim Suma Yalamanchili Mario L. Calcagno Stephen C. Woods Randy J. Seeley
author_facet	Ruth Gutierrez-Aguilar Ruth Gutierrez-Aguilar Bernadette E. Grayson Dong-Hoon Kim Suma Yalamanchili Mario L. Calcagno Stephen C. Woods Randy J. Seeley
author_sort	Ruth Gutierrez-Aguilar
title	CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis
title_short	CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis
title_full	CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis
title_fullStr	CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis
title_full_unstemmed	CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis
title_sort	cns gnpda2 does not control appetite, but regulates glucose homeostasis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/929cf6355a8040a892243288d86fea76
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CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis

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