The Rapid Anorectic Response to a Threonine Imbalanced Diet is decreased by Injection of Threonine into the Anterior Piriform Cortex of Rats

Russell, Matthew; Koehnle, Thomas J.; Barrett, Jennifer; Blevins, James E.; Gietzen, Dorothy W.

doi:10.1080/1028415031000151567

Cited by 27 publications

(22 citation statements)

References 8 publications

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“…This learned aversion is mediated by critical molecular events within the anterior piriform cortex (APC), in particular, the accumulation of uncharged tRNAs and the resultant activation of the GCN2 kinase (52,112). Replacement of the missing amino acid locally within the APC, or deletion of GCN2, is sufficient to attenuate this learned aversion (52,74,113). These observations provide clear support for a detection of protein quality (amino acid profile).…”

Section: Effects Of High-protein Diets On Food Intakementioning

confidence: 63%

“…Interestingly, in this case, the detection is not of amino acid excess or deficiency, but the imbalance of the amino acid profile, which results in an accumulation of uncharged tRNAs for the missing amino acid (52). This accumulation of uncharged tRNA activates the kinase GCN2 locally within the APC, and replacement of the missing amino acid locally within the APC or deletion of GCN2 is sufficient to attenuate this learned aversion (52,74,113). As such, these observations clearly demonstrate a physiologically relevant effect of amino acids acting directly in the brain.…”

Section: Physiological Signals Of Proteinmentioning

confidence: 90%

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Homeostatic regulation of protein intake: in search of a mechanism

Morrison

Reed

Henagan

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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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. High-protein diets tend to reduce intake, low-protein diets tend to increase intake, and rodent models seem to self-select between diets in order to meet protein requirements and avoid diets that are imbalanced in amino acids. Recent work suggests that the amino acid leucine regulates food intake by altering mTOR and AMPK signaling in the hypothalamus, while activation of GCN2 within the anterior piriform cortex contributes to the detection and avoidance of amino acid-imbalanced diets. This review focuses on the role that these and other signaling systems may play in mediating the homeostatic regulation of protein balance, and in doing so, highlights our lack of knowledge regarding the physiological and neurobiological mechanisms that might underpin such a regulatory phenomenon.

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Section: Effects Of High-protein Diets On Food Intakementioning

confidence: 63%

Section: Physiological Signals Of Proteinmentioning

confidence: 90%

Homeostatic regulation of protein intake: in search of a mechanism

Morrison

Reed

Henagan

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Injection of nmol amounts of L-threoninol or L-leucinol, but neither Dthreoninol nor a dispensable AA, into the APC decreases food intake at 20 min, the same as eating an IAA-devoid diet. These are the reciprocal of studies in which nmols of the limiting IAA, microinjected into the APC, restore feeding of an IAA-deficient or -imbalanced diet (10,82,96). The next step in the yeast GCN pathway is the activation of the GCN2 kinase (52), which dimerizes and autophosphorylates when uncharged tRNA binds to a nonselective histidine tRNA site (HisRS; 88,110).…”

Section: General Amino Acid-control Pathwaymentioning

confidence: 99%

Mechanisms of Food Intake Repression in Indispensable Amino Acid Deficiency

2007

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Animals reject diets that lead to indispensable amino acid (IAA) depletion or deficiency. This behavior is adaptive, as continued IAA depletion is incompatible with maintenance of protein synthesis and survival. Following rejection of the diet, animals begin foraging for a better IAA source and develop conditioned aversions to cues associated with the deficient diet. These responses require a sensory system to detect the IAA depletion and alert the appropriate neural circuitry for the behavior. The chemosensor for IAA deprivation is in the highly excitable anterior piriform cortex (APC) of the brain. Recently, the well-conserved general AA control non-derepressing system of yeast was discovered to be activated by IAA deprivation via uncharged tRNA in mammalian APC. This system provides the sensory limb of the mechanism for recognition of IAA depletion that leads to activation of the APC, diet rejection, and subsequent adaptive strategies.

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“…A large body of literature indicates that changes in dietary protein influence feeding behavior (1,3,17,25,28,(33)(34)(35). In addition, variations in individual amino acids are also detected by a central nutrient-sensing system, as illustrated by the rapid aversion that develops to diets that are severely imbalanced for an essential amino acid (12,16,29,31) and by the fact that rats will preferentially self-select between two imbalanced diets to meet amino acid requirements (11). Taken together, the above observations support the existence of neural mechanisms that sense and respond to changes in protein or amino acid availability.…”

mentioning

confidence: 99%

Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism

Morrison¹,

Xi²,

White³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

159

115

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Metabolic fuels act on hypothalamic neurons to regulate feeding behavior and energy homeostasis, but the signaling mechanisms mediating these effects are not fully clear. Rats placed on a low-protein diet (10% of calories) exhibited increased food intake ( P < 0.05) and hypothalamic Agouti-related protein ( Agrp) gene expression ( P = 0.002). Direct intracerebroventricular injection of either an amino acid mixture (RPMI 1640) or leucine alone (1 μg) suppressed 24-h food intake ( P < 0.05), indicating that increasing amino acid concentrations within the brain is sufficient to suppress food intake. To define a cellular mechanism for these direct effects, GT1–7 hypothalamic cells were exposed to low amino acids for 16 h. Decreasing amino acid availability increased Agrp mRNA levels in GT1–7 cells ( P < 0.01), and this effect was attenuated by replacement of the amino acid leucine ( P < 0.05). Acute exposure to elevated amino acid concentrations increased ribosomal protein S6 kinase phosphorylation via a rapamycin-sensitive mechanism, suggesting that amino acids directly stimulated mammalian target of rapamycin (mTOR) signaling. To test whether mTOR signaling contributes to amino acid inhibition of Agrp gene expression, GT1–7 cells cultured in either low or high amino acids for 16 h and were also treated with rapamcyin (50 nM). Rapamycin treatment increased Agrp mRNA levels in cells exposed to high amino acids ( P = 0.01). Taken together, these observations indicate that amino acids can act within the brain to inhibit food intake and that a direct, mTOR-dependent inhibition of Agrp gene expression may contribute to this effect.

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The Rapid Anorectic Response to a Threonine Imbalanced Diet is decreased by Injection of Threonine into the Anterior Piriform Cortex of Rats

Cited by 27 publications

References 8 publications

Homeostatic regulation of protein intake: in search of a mechanism

Homeostatic regulation of protein intake: in search of a mechanism

Mechanisms of Food Intake Repression in Indispensable Amino Acid Deficiency

Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism

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