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food intake gcn2

Thomas Laeger, Diana C Albarado, Susan J Burke, Lexus Trosclair, John W Hedgepeth, Hans-Rudolf Berthoud, Thomas W Gettys, J Jason Collier, Heike Münzberg, Christopher D Morrison
FGF21 contributes to the metabolic response to dietary protein restriction, and prior data implicate GCN2 as the amino acid sensor linking protein restriction to FGF21 induction. Here, we demonstrate the persistent and essential role of FGF21 in the metabolic response to protein restriction. We show that Fgf21 KO mice are fully resistant to low protein (LP)-induced changes in food intake, energy expenditure (EE), body weight gain, and metabolic gene expression for 6 months. Gcn2 KO mice recapitulate this phenotype, but LP-induced effects on food intake, EE, and body weight subsequently begin to appear after 14 days on diet...
July 19, 2016: Cell Reports
Jong Gab Jung, Sang-A Yi, Sung-E Choi, Yup Kang, Tae Ho Kim, Ja Young Jeon, Myung Ae Bae, Jin Hee Ahn, Hana Jeong, Eun Sook Hwang, Kwan-Woo Lee
The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice...
December 2015: Molecules and Cells
Gabriel J Wilson, Brittany A Lennox, Pengxiang She, Emily T Mirek, Rana J T Al Baghdadi, Michael E Fusakio, Joseph L Dixon, Gregory C Henderson, Ronald C Wek, Tracy G Anthony
The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake...
February 15, 2015: American Journal of Physiology. Endocrinology and Metabolism
Thomas Laeger, Tara M Henagan, Diana C Albarado, Leanne M Redman, George A Bray, Robert C Noland, Heike Münzberg, Susan M Hutson, Thomas W Gettys, Michael W Schwartz, Christopher D Morrison
Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet...
September 2014: Journal of Clinical Investigation
Anne-Catherine Maurin, Alexandre Benani, Anne Lorsignol, Xavier Brenachot, Laurent Parry, Valérie Carraro, Christophe Guissard, Julien Averous, Céline Jousse, Alain Bruhat, Cédric Chaveroux, Wafa B'chir, Yuki Muranishi, David Ron, Luc Pénicaud, Pierre Fafournoux
The reversible phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) is a highly conserved signal implicated in the cellular adaptation to numerous stresses such as the one caused by amino acid limitation. In response to dietary amino acid deficiency, the brain-specific activation of the eIF2α kinase GCN2 leads to food intake inhibition. We report here that GCN2 is rapidly activated in the mediobasal hypothalamus (MBH) after consumption of a leucine-deficient diet. Furthermore, knockdown of GCN2 in this particular area shows that MBH GCN2 activity controls the onset of the aversive response...
February 13, 2014: Cell Reports
Marianne Bjordal, Nathalie Arquier, Julie Kniazeff, Jean Philippe Pin, Pierre Léopold
The brain is the central organizer of food intake, matching the quality and quantity of the food sources with organismal needs. To ensure appropriate amino acid balance, many species reject a diet lacking one or several essential amino acids (EAAs) and seek out a better food source. Here, we show that, in Drosophila larvae, this behavior relies on innate sensing of amino acids in dopaminergic (DA) neurons of the brain. We demonstrate that the amino acid sensor GCN2 acts upstream of GABA signaling in DA neurons to promote avoidance of the EAA-deficient diet...
January 30, 2014: Cell
Jordan Gallinetti, Eylul Harputlugil, James R Mitchell
DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR...
January 1, 2013: Biochemical Journal
Christopher D Morrison, Scott D Reed, Tara M Henagan
Free-living organisms must procure adequate nutrition by negotiating an environment in which both the quality and quantity of food vary markedly. Recent decades have seen marked progress in our understanding of neural regulation of feeding behavior. However, this progress has occurred largely in the context of energy intake, despite the fact that food intake is influenced by more than just the energy content of the diet. A large number of behavioral studies indicate that both the quantity and quality of dietary protein can markedly influence food intake...
April 15, 2012: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Wei Peng, Lauren Robertson, Jordan Gallinetti, Pedro Mejia, Sarah Vose, Allison Charlip, Timothy Chu, James R Mitchell
Dietary restriction, or reduced food intake without malnutrition, increases life span, health span, and acute stress resistance in model organisms from yeast to nonhuman primates. Although dietary restriction is beneficial for human health, this treatment is not widely used in the clinic. Here, we show that short-term, ad libitum feeding of diets lacking essential nutrients increased resistance to surgical stress in a mouse model of ischemia reperfusion injury. Dietary preconditioning by 6 to 14 days of total protein deprivation, or removal of the single essential amino acid tryptophan, protected against renal and hepatic ischemic injury, resulting in reduced inflammation and preserved organ function...
January 25, 2012: Science Translational Medicine
Anne-Catherine Maurin, Cédric Chaveroux, Sarah Lambert-Langlais, Valérie Carraro, Céline Jousse, Alain Bruhat, Julien Averous, Laurent Parry, David Ron, Josette Alliot, Pierre Fafournoux
PURPOSE: Selection of a balanced diet has a determinant impact on human health. Individual food preferences involve socio-cultural as well as physiological factors and evolve during aging. In mammals, physiological mechanisms governing food choices appear to require the sensing of nutrient concentrations in diet. This is particularly the case for dietary amino acids that are sensed by the protein kinase GCN2. It has been reported that GCN2 is involved in the adaptive response to amino acid imbalanced diets at the level of food intake and lipid metabolism...
February 2012: European Journal of Nutrition
Piyawan Bunpo, Judy K Cundiff, Rachel B Reinert, Ronald C Wek, Carla J Aldrich, Tracy G Anthony
Amino acid starvation by asparaginase (ASNase) enhances phosphorylation of eukaryotic initiation factor 2 (eIF2) by general control nonderepressible 2 (GCN2) kinase, leading to reduced global mRNA translation rates. This conserves energy and allows cells time to reprogram stress-related gene expression to alleviate cell injury. This study addressed the importance of GCN2 for the immune system to adapt to amino acid starvation by ASNase. GCN2(+/+) and GCN2(-/-) mice were injected once daily with ASNase or saline for up to 7 d...
November 2010: Journal of Nutrition
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