Fructose-Induced Hypothalamic AMPK Activation Stimulates Hepatic PEPCK and Gluconeogenesis due to Increased Corticosterone Levels


Autoria(s): Kinote, Andrezza; Faria, Juliana A.; Roman, Erika A.; Solon, Carina; Razolli, Daniela S.; Ignacio-Souza, Leticia M.; Sollon, Carolina S.; Nascimento, Lucas Ferreira do; de Araujo, Thiago M.; Barbosa, Ana Paula L.; Santos, Camilo de Lellis; Velloso, Lício Augusto; Silva, Silvana Auxiliadora Bordin da; Anhê, Gabriel Forato
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

14/10/2013

14/10/2013

2012

Resumo

Fructose consumption causes insulin resistance and favors hepatic gluconeogenesis through mechanisms that are not completely understood. Recent studies demonstrated that the activation of hypothalamic 5'-AMP-activated protein kinase (AMPK) controls dynamic fluctuations in hepatic glucose production. Thus, the present study was designed to investigate whether hypothalamic AMPK activation by fructose would mediate increased gluconeogenesis. Both ip and intracerebroventricular (icv) fructose treatment stimulated hypothalamic AMPK and acetyl-CoA carboxylase phosphorylation, in parallel with increased hepatic phosphoenolpyruvate carboxy kinase (PEPCK) and gluconeogenesis. An increase in AMPK phosphorylation by icv fructose was observed in the lateral hypothalamus as well as in the paraventricular nucleus and the arcuate nucleus. These effects were mimicked by icv 5-amino-imidazole-4-carboxamide-1-beta-D-ribofuranoside treatment. Hypothalamic AMPK inhibition with icv injection of compound C or with injection of a small interfering RNA targeted to AMPK alpha 2 in the mediobasal hypothalamus (MBH) suppressed the hepatic effects of ip fructose. We also found that fructose increased corticosterone levels through a mechanism that is dependent on hypothalamic AMPK activation. Concomitantly, fructose-stimulated gluconeogenesis, hepatic PEPCK expression, and glucocorticoid receptor binding to the PEPCK gene were suppressed by pharmacological glucocorticoid receptor blockage. Altogether the data presented herein support the hypothesis that fructose-induced hypothalamic AMPK activation stimulates hepatic gluconeogenesis by increasing corticosterone levels. (Endocrinology 153: 3633-3645, 2012)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Conselho Nacional de Pesquisa (CNPq)

Conselho Nacional de Pesquisa (CNPq)

Identificador

ENDOCRINOLOGY, CHEVY CHASE, v. 153, n. 8, supl. 4, Part 1-2, pp. 3633-3645, AUG, 2012

0013-7227

http://www.producao.usp.br/handle/BDPI/34474

10.1210/en.2012-1341

http://dx.doi.org/10.1210/en.2012-1341

Idioma(s)

eng

Publicador

ENDOCRINE SOC

CHEVY CHASE

Relação

ENDOCRINOLOGY

Direitos

closedAccess

Copyright ENDOCRINE SOC

Palavras-Chave #PROTEIN-KINASE #GLUCOSE-TRANSPORTER #FOOD-INTAKE #LIPID-METABOLISM #FATTY LIVER #MALONYL-COA #RATS #INSULIN #RESPONSES #HYPOGLYCEMIA #ENDOCRINOLOGY & METABOLISM
Tipo

article

original article

publishedVersion