Artículos de revistas
Hypothalamic Ampk Activation Blocks Lipopolysaccharide Inhibition Of Glucose Production In Mice Liver
Registro en:
Molecular And Cellular Endocrinology. , v. 381, n. 1/Fev, p. 88 - 96, 2013.
3037207
10.1016/j.mce.2013.07.018
2-s2.0-84882737443
Autor
Santos G.A.
Moura R.F.
Vitorino D.C.
Roman E.A.F.R.
Torsoni A.S.
Velloso L.A.
Torsoni M.A.
Institución
Resumen
Endotoxic hypoglycaemia has an important role in the survival rates of septic patients. Previous studies have demonstrated that hypothalamic AMP-activated protein kinase (hyp-AMPK) activity is sufficient to modulate glucose homeostasis. However, the role of hyp-AMPK in hypoglycaemia associated with endotoxemia is unknown. The aims of this study were to examine hyp-AMPK dephosphorylation in lipopolysaccharide (LPS)-treated mice and to determine whether pharmacological hyp-AMPK activation could reduce the effects of endotoxemia on blood glucose levels. LPS-treated mice showed reduced food intake, diminished basal glycemia, increased serum TNF-α and IL-1β levels and increased hypothalamic p-TAK and TLR4/MyD88 association. These effects were accompanied by hyp-AMPK/ACC dephosphorylation. LPS-treated mice also showed diminished liver expression of PEPCK/G6Pase, reduction in p-FOXO1, p-AMPK, p-STAT3 and p-JNK level and glucose production. Pharmacological hyp-AMPK activation blocked the effects of LPS on the hyp-AMPK phosphorylation, liver PEPCK expression and glucose production. Furthermore, the effects of LPS were TLR4-dependent because hyp-AMPK phosphorylation, liver PEPCK expression and fasting glycemia were not affected in TLR4-mutant mice. These results suggest that hyp-AMPK activity may be an important pharmacological target to control glucose homeostasis during endotoxemia. © 2013 Elsevier Ireland Ltd. 381 1/Fev 88 96 Abram, M., Vu kovic, D., Wraber, B., Doric, M., Plasma cytokine response in mice with bacterial infection (2000) Mediators Inflamm., 9, pp. 229-234 Borges, B.C., Rorato, R., Avraham, Y., da Silva, L.E., Castro, M., Vorobiav, L., Berry, E., Elias, L.L., Leptin resistance and desensitization of hypophagia during prolonged inflammatory challenge (2011) Am. J. Physiol. Endocrinol. Metab., 300. , E858-69 Carvalheira, J.B., Torsoni, M.A., Ueno, M., Amaral, M.E., Araujo, E.P., Velloso, L.A., Gontijo, J.A., Saad, M.J., Cross-talk between the insulin and leptin signaling systems in rat hypothalamus (2005) Obes Res., 13, pp. 48-57 Cesquini, M., Stoppa, G.R., Prada, P.O., Torsoni, A.S., Romanatto, T., Souza, A., Saad, M.J., Torsoni, M.A., Citrate diminishes hypothalamic acetyl-CoA carboxylase phosphorylation and modulates satiety signals and hepatic mechanisms involved in glucose homeostasis in rats (2008) Life Sci., 82, pp. 1262-1271 Chanda, D., Kim, D.K., Li, T., Kim, Y.H., Koo, S.H., Lee, C.H., Chiang, J.Y., Choi, H.S., Cannabinoid receptor type 1 (CB1R) signaling regulates hepatic gluconeogenesis via induction of endoplasmic reticulum-bound transcription factor cAMP-responsive element-binding protein H (CREBH) in primary hepatocytes (2011) J. Biol. Chem., 286, pp. 27971-27979 Chari, M., Lam, C.K., Wang, P.Y., Lam, T.K., Activation of central lactate metabolism lowers glucose production in uncontrolled diabetes and diet-induced insulin resistance (2008) Diabetes, 57, pp. 836-840 Chichelnitskiy, E., Vegiopoulos, A., Berriel Diaz, M., Ziegler, A., Kleiman, A., Rauch, A., Tuckermann, J., Herzig, S., In vivo phosphoenolpyruvate carboxykinase promoter mapping identifies disrupted hormonal synergism as a target of inflammation during sepsis in mice (2009) Hepatology, 50, pp. 1963-1971 Cornell, R.P., Endogenous gut-derived bacterial endotoxin tonically primes pancreatic secretion of insulin in normal rats (1985) Diabetes, 34, pp. 1253-1259 De Souza, C.T., Frederico, M.J., da Luz, G., Cintra, D.E., Ropelle, E.R., Pauli, J.R., Velloso, L.A., Acute exercise reduces hepatic glucose production through inhibition of the Foxo1/HNF-4alpha pathway in insulin resistant mice (2010) J. Physiol., 588, pp. 2239-2253 Feingold, K.R., Moser, A., Shigenaga, J.K., Grunfeld, C., Inflammation inhibits the expression of phosphoenolpyruvate carboxykinase in liver and adipose tissue (2012) Innate Immun., 18, pp. 231-240 Finck, B.N., Kelley, K.W., Dantzer, R., Johnson, R.W., In vivo and in vitro evidence for the involvement of tumor necrosis factor-alpha in the induction of leptin by lipopolysaccharide (1998) Endocrinology, 139, pp. 2278-2283 Friedman, J.E., Sun, Y., Ishizuka, T., Farrell, C.J., McCormack, S.E., Herron, L.M., Hakimi, P., Yun, J.S., Phosphoenolpyruvate carboxykinase (GTP) gene transcription and hyperglycemia are regulated by glucocorticoids in genetically obese db/db transgenic mice (1997) J. Biol. Chem., 272, pp. 31475-31481 Gamelli, R.L., Liu, H., He, L.K., Hofmann, C.A., Augmentations of glucose uptake and glucose transporter-1 in macrophages following thermal injury and sepsis in mice (1996) J. Leukoc. Biol., 59, pp. 639-647 Gao, S., Kinzig, K.P., Aja, S., Scott, K.A., Keung, W., Kelly, S., Strynadka, K., Moran, T.H., Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake (2007) Proc. Natl. Acad. Sci. USA, 104, pp. 17358-17363 Han, S.M., Namkoong, C., Jang, P.G., Park, I.S., Hong, S.W., Katakami, H., Chun, S., Kim, M.S., Hypothalamic AMP-activated protein kinase mediates counter-regulatory responses to hypoglycaemia in rats (2005) Diabetologia, 48, pp. 2170-2178 Hardie, D.G., Pan, D.A., Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase (2002) Biochem. Soc. Trans., 30, pp. 1064-1070 Hart, B.L., Biological basis of the behavior of sick animals (1988) Neurosci. Biobehav Rev., 12, pp. 123-137 Herzig, S., Long, F., Jhala, U.S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Montminy, M., CREB regulates hepatic gluconeogenesis through the coactivator PGC-1 (2001) Nature, 413, pp. 179-183 Hill, M., McCallum, R., Altered transcriptional regulation of phosphoenolpyruvate carboxykinase in rats following endotoxin treatment (1991) J. Clin. Invest., 88, pp. 811-816 Hosoi, T., Okuma, Y., Kawagishi, T., Qi, X., Matsuda, T., Nomura, Y., Bacterial endotoxin induces STAT3 activation in the mouse brain (2004) Brain Res., 1023, pp. 48-53 Inoue, H., Ogawa, W., Asakawa, A., Okamoto, Y., Nishizawa, A., Matsumoto, M., Teshigawara, K., Kasuga, M., Role of hepatic STAT3 in brain-insulin action on hepatic glucose production (2006) Cell Metab., 3, pp. 267-275 Inoue, H., Ogawa, W., Ozaki, M., Haga, S., Matsumoto, M., Furukawa, K., Hashimoto, N., Kasuga, M., Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo (2004) Nat. Med., 10, pp. 168-174 Kim, E.K., Miller, I., Aja, S., Landree, L.E., Pinn, M., McFadden, J., Kuhajda, F.P., Ronnett, G.V., C75, a fatty acid synthase inhibitor, reduces food intake via hypothalamic AMP-activated protein kinase (2004) J. Biol. Chem., 279, pp. 19970-19976 Kim, K.W., Donato, J., Berglund, E.D., Choi, Y.H., Kohno, D., Elias, C.F., Depinho, R.A., Elmquist, J.K., FOXO1 in the ventromedial hypothalamus regulates energy balance (2012) J. Clin. Invest., 122, pp. 2578-2589 Kim, K.W., Sohn, J.W., Kohno, D., Xu, Y., Williams, K., Elmquist, J.K., SF-1 in the ventral medial hypothalamic nucleus: a key regulator of homeostasis (2011) Mol. Cell Endocrinol., 336, pp. 219-223 Koo, S.H., Flechner, L., Qi, L., Zhang, X., Screaton, R.A., Jeffries, S., Hedrick, S., Montminy, M., The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism (2005) Nature, 437, pp. 1109-1111 Krinsley, J.S., Grover, A., Severe hypoglycemia in critically ill patients: risk factors and outcomes (2007) Crit. Care Med., 35, pp. 2262-2267 Lam, T.K., Gutierrez-Juarez, R., Pocai, A., Rossetti, L., Regulation of blood glucose by hypothalamic pyruvate metabolism (2005) Science, 309, pp. 943-947 Lam, T.K., Pocai, A., Gutierrez-Juarez, R., Obici, S., Bryan, J., Aguilar-Bryan, L., Schwartz, G.J., Rossetti, L., Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis (2005) Nat. Med., 11, pp. 320-327 Lang, C.H., Spolarics, Z., Ottlakan, A., Spitzer, J.J., Effect of high-dose endotoxin on glucose production and utilization (1993) Metabolism, 42, pp. 1351-1358 Lopez, M., Varela, L., Vazquez, M.J., Rodriguez-Cuenca, S., Gonzalez, C.R., Velagapudi, V.R., Morgan, D.A., Vidal-Puig, A., Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance (2010) Nat. Med., 16, pp. 1001-1008 Maitra, S.R., Gestring, M.L., El-Maghrabi, M.R., Lang, C.H., Henry, M.C., Endotoxin-induced alterations in hepatic glucose-6-phosphatase activity and gene expression (1999) Mol. Cell Biochem., 196, pp. 79-83 Mastronardi, C.A., Yu, W.H., Rettori, V., McCann, S., Lipopolysaccharide-induced leptin release is not mediated by nitric oxide, but is blocked by dexamethasone (2000) Neuroimmunomodulation, 8, pp. 91-97 McCrimmon, R.J., Fan, X., Ding, Y., Zhu, W., Jacob, R.J., Sherwin, R.S., Potential role for AMP-activated protein kinase in hypoglycemia sensing in the ventromedial hypothalamus (2004) Diabetes, 53, pp. 1953-1958 McCrimmon, R.J., Shaw, M., Fan, X., Cheng, H., Ding, Y., Vella, M.C., Zhou, L., Sherwin, R.S., Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia (2008) Diabetes, 57, pp. 444-450 McKinley, M.J., Allen, A.M., May, C.N., McAllen, R.M., Oldfield, B.J., Sly, D., Mendelsohn, F.A., Neural pathways from the lamina terminalis influencing cardiovascular and body fluid homeostasis (2001) Clin. Exp. Pharmacol. Physiol., 28, pp. 990-992 Melo, A.M., Bittencourt, P., Nakutis, F.S., Silva, A.P., Cursino, J., Santos, G.A., Ashino, N.G., Torsoni, M.A., Solidago chilensis Meyen hydroalcoholic extract reduces JNK/IkappaB pathway activation and ameliorates insulin resistance in diet-induced obesity mice (2011) Exp. Biol. Med. (Maywood)., 236, pp. 1147-1155 Michelotto, J.B., Carvalheira, J.B., Saad, M.J., Gontijo, J.A., Effects of intracerebroventricular insulin microinjection on renal sodium handling in kidney-denervated rats (2002) Brain Res. Bull., 57, pp. 613-618 Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.B., Lee, A., Xue, B., Mu, J., Kahn, B.B., AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus (2004) Nature, 428, pp. 569-574 Namkoong, C., Kim, M.S., Jang, P.G., Han, S.M., Park, H.S., Koh, E.H., Lee, W.J., Lee, K.U., Enhanced hypothalamic AMP-activated protein kinase activity contributes to hyperphagia in diabetic rats (2005) Diabetes, 54, pp. 63-68 Obici, S., Feng, Z., Arduini, A., Conti, R., Rossetti, L., Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production (2003) Nat. Med., 9, pp. 756-761 Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., Rossetti, L., Central administration of oleic acid inhibits glucose production and food intake (2002) Diabetes, 51, pp. 271-275 Obici, S., Zhang, B.B., Karkanias, G., Rossetti, L., Hypothalamic insulin signaling is required for inhibition of glucose production (2002) Nat. Med., 8, pp. 1376-1382 Olson, J.K., Miller, S.D., Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs (2004) J. Immunol., 173, pp. 3916-3924 Pilkis, S.J., Granner, D.K., Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis (1992) Annu. Rev. Physiol., 54, pp. 885-909 Pocai, A., Lam, T.K., Gutierrez-Juarez, R., Obici, S., Schwartz, G.J., Bryan, J., Aguilar-Bryan, L., Rossetti, L., Hypothalamic K(ATP) channels control hepatic glucose production (2005) Nature, 434, pp. 1026-1031 Pocai, A., Morgan, K., Buettner, C., Gutierrez-Juarez, R., Obici, S., Rossetti, L., Central leptin acutely reverses diet-induced hepatic insulin resistance (2005) Diabetes, 54, pp. 3182-3189 Puigserver, P., Rhee, J., Donovan, J., Walkey, C.J., Yoon, J.C., Oriente, F., Kitamura, Y., Spiegelman, B.M., Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction (2003) Nature, 423, pp. 550-555 Puigserver, P., Spiegelman, B.M., Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator (2003) Endocr. Rev., 24, pp. 78-90 Ross, R., Wang, P.Y., Chari, M., Lam, C.K., Caspi, L., Ono, H., Muse, E.D., Lam, T.K., Hypothalamic protein kinase C regulates glucose production (2008) Diabetes, 57, pp. 2061-2065 Saha, A.K., Ruderman, N.B., Malonyl-CoA and AMP-activated protein kinase: an expanding partnership (2003) Mol. Cell Biochem., 253, pp. 65-70 Saltiel, A.R., New perspectives into the molecular pathogenesis and treatment of type 2 diabetes (2001) Cell, 104, pp. 517-529 Soraya, H., Farajnia, S., Khani, S., Rameshrad, M., Khorrami, A., Banani, A., Maleki-Dizaji, N., Garjani, A., Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: Are AMPK and TLRs connected? (2012) Int. Immunopharmacol., 14, pp. 785-791 Steinberg, G.R., Michell, B.J., van Denderen, B.J., Watt, M.J., Carey, A.L., Fam, B.C., Andrikopoulos, S., Kemp, B.E., Tumor necrosis factor alpha-induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling (2006) Cell Metab., 4, pp. 465-474 Stoppa, G.R., Cesquini, M., Roman, E.A., Prada, P.O., Torsoni, A.S., Romanatto, T., Saad, M.J., Torsoni, M.A., Intracerebroventricular injection of citrate inhibits hypothalamic AMPK and modulates feeding behavior and peripheral insulin signaling (2008) J. Endocrinol., 198, pp. 157-168 Tadie, J.M., Bae, H.B., Deshane, J.S., Bell, C.P., Lazarowski, E.R., Chaplin, D.D., Thannickal, V.J., Zmijewski, J.W., Toll-like receptor 4 engagement inhibits adenosine 5'-monophosphate-activated protein kinase activation through a high mobility group box 1 protein-dependent mechanism (2012) Mol Med., 18, pp. 659-668 Vogel, S.N., Henricson, B.E., Neta, R., Roles of interleukin-1 and tumor necrosis factor in lipopolysaccharide-induced hypoglycemia (1991) Infect Immun., 59, pp. 2494-2498 Waeschle, R.M., Moerer, O., Hilgers, R., Herrmann, P., Neumann, P., Quintel, M., The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability (2008) Crit. Care., 12, pp. R129 Xue, B., Yang, Z., Wang, X., Shi, H., Omega-3 polyunsaturated fatty acids antagonize macrophage inflammation via activation of AMPK/SIRT1 pathway (2012) PLoS One., 7, pp. e45990 Yamawaki, Y., Kimura, H., Hosoi, T., Ozawa, K., MyD88 plays a key role in LPS-induced Stat3 activation in the hypothalamus (2010) Am .J. Physiol. Regul. Integr. Comp. Physiol., 298. , R403-10 Yang, C.S., Lam, C.K., Chari, M., Cheung, G.W., Kokorovic, A., Gao, S., Leclerc, I., Lam, T.K., Hypothalamic AMP-activated protein kinase regulates glucose production (2010) Diabetes, 59, pp. 2435-2443