Genetic variance contributes to ingestive processes: A survey of 2-deoxy-d-glucose-induced feeding in eleven inbred mouse strains

Lewis, Sarah R.; Ahmed, Sabrina; Khaimova, Eleonora; Israel, Yuriy; Singh, Amreeta; Kandov, Yakov; Kest, Benjamin; Bodnar, Richard J.

doi:10.1016/j.physbeh.2005.12.002

Cited by 15 publications

(15 citation statements)

References 61 publications

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“…However, the behavioral effects of decreased glucose concentration do not necessarily require prior experience linking low blood glucose to specific behaviors, suggesting that the behavioral response to glucoprivation is innate. For example, a single injection of 2-deoxyglucose, a non-metabolizable glucose competitor, is sufficient to induce robust increases in food intake in several strains of mice (independent of previous experience associating food pellets with glucoprivation 45 ). A single injection of 2-deoxyglucose is also sufficient to induce substantial increases in licks for glucose in sweet-blind mice that have never received this drug, indicating that the effect is not dependant on taste 3 .…”

Section: Discussionmentioning

confidence: 99%

Leptin regulates the reward value of nutrient

et al. 2011

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We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake.

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Section: Discussionmentioning

confidence: 99%

Leptin regulates the reward value of nutrient

et al. 2011

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“…Glucose is the primary physiological fuel for the brain in the fed state, whereas ketones become primary fuel during prolonged food deprivation or when conditions leading to elevated circulating ketones, e.g., the ketogenic diet, prevail. Glucose rapidly activates or inhibits hypothalamic neuronal firing (28) and has long been known to suppress food intake (19). Although little is known about the molecular mechanism of hypothalamic glucose sensing per se, it is likely that AMPK plays an important role (4,5).…”

Section: Discussionmentioning

confidence: 99%

“…Malonyl-CoA is synthesized de novo from glucose. Glucose inhibits food intake, and blockage of glucose utilization (19) or uptake increases food intake (20) although the precise role for neuronal glucose sensing is not well understood (21). These observations are consistent with a role for malonyl-CoA and suggest that hypothalamic glucose sensing may be a major regulatory mechanism for malonyl-CoA.…”

mentioning

confidence: 81%

Regulation of hypothalamic malonyl-CoA by central glucose and leptin

Wolfgang

Hun

Sidhaye

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

112

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Hypothalamic malonyl-CoA has been shown to function in global energy homeostasis by modulating food intake and energy expenditure. Little is known, however, about the regulation of malonyl-CoA concentration in the central nervous system. To address this issue we investigated the response of putative intermediates in the malonyl-CoA pathway to metabolic and endocrine cues, notably those provoked by glucose and leptin. Hypothalamic malonyl-CoA rises in proportion to the carbohydrate content of the diet consumed after food deprivation. Malonyl-CoA concentration peaks 1 h after refeeding or after peripheral glucose administration. This response depends on the dose of glucose administered and is blocked by the i.c.v. administration of an inhibitor of glucose metabolism, 2-deoxyglucose (2-DG). The kinetics of change in hypothalamic malonyl-CoA after glucose administration is coincident with the suppression of phosphorylation of AMP kinase and acetyl-CoA carboxylase. Blockade of glucose utilization in the CNS by i.c.v. 2-DG prevented the effects of glucose on 5AMP-activated protein kinase, malonyl-CoA, hypothalamic neuropeptide expression, and food intake. Finally, we showed that leptin can increase hypothalamic malonyl-CoA and that the increase is additive with glucose administration. Leptin-deficient ob/ob mice, however, showed no defect in the glucose-or refeeding-induced rise in hypothalamic malonyl-CoA after food deprivation, demonstrating that leptin was not required for this effect. These studies show that hypothalamic malonyl-CoA responds to the level of circulating glucose and leptin, both of which affect energy homeostasis.acetyl-CoA carboxylase ͉ AMP kinase ͉ carnitine palmitoyl-transferase 1c ͉ fatty acid synthase A n interconnected endocrine and neuroendocrine system controls food intake and energy expenditure (1). Recently, a new pathway for maintaining energy homeostasis has become evident that relies on an ancient nutrient-sensing pathway whereby the CNS directly monitors energy needs by sampling cellular adenine nucleotide levels and responds by directing hunger and peripheral energy expenditure (2, 3). Neural cellular energy status is monitored through AMPK, which directly senses the [AMP]/[ATP] ratio. The AMPK system provides a rapid means of detecting energy status not reliant directly on endocrine signals. The activation of AMPK leads to the inhibition of the key regulatory enzyme of fatty acid synthesis, acetyl-CoA carboxylase (ACC). The activity of this enzyme is an indicator of energy surplus and is thought to be one of the mechanisms by which energy homeostasis is mediated. Several enzymes that are involved in fatty acid metabolism have been implicated in the CNS control of energy homeostasis including AMPK (4-7), ACC (8, 9), fatty acid synthase (FAS) (8, 10), carnitine palmitoyltransferase 1 (CPT1) (11, 12), and stearoyl-CoA desaturase 1 (13). Because fatty acid synthesis is a process that occurs primarily during energy surplus, it is not surprising that this system has evolved as a means to r...

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“…Intravenous infusions of 2-DG at the smallest dose known to produce significant behavioral effects in C57BL/6 mice (400 mg/kg) (Lewis et al, 2006) produced a robust decrease in extracellular dopamine levels in striatum (34.7 Ϯ 9.5% dopamine concentration of initial baseline; one-sample t test against baseline concentration level of 100%, t ϭ Ϫ6.8; p Ͻ 0.007) (Fig. 6 B).…”

Section: Disrupting Glucose Metabolism Inhibits Dopamine Release In Dmentioning

confidence: 93%

Nutrient Selection in the Absence of Taste Receptor Signaling

Ren¹,

Ferreira²,

Zhou³

et al. 2010

Journal of Neuroscience

142

161

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When allowed to choose between different macronutrients, most animals display a strong attraction toward carbohydrates compared with proteins. It remains uncertain, however, whether this food selection pattern depends primarily on the sensory properties intrinsic to each nutrient or, alternatively, metabolic signals can act independently of the hedonic value of sweetness to stimulate elevated sugar intake. Here we show that Trpm5 Ϫ/Ϫ mice, which lack the cellular mechanisms required for sweet and several forms of L-amino acid taste transduction, develop a robust preference for D-glucose compared with isocaloric L-serine independently of the perception of sweetness. Moreover, a close relationship was found between glucose oxidation and taste-independent nutrient intake levels, with animals increasing intake as a function of glucose oxidation rates. Furthermore, microdialysis measurements revealed nutrient-specific dopaminergic responses in accumbens and dorsal striatum during intragastric infusions of glucose or serine. Specifically, intragastric infusions of glucose induced significantly higher levels of dopamine release compared with isocaloric serine in both ventral and dorsal striatum. Intragastric stimulation of dopamine release seemed to depend on glucose utilization, because administration of an anti-metabolic glucose analog resulted in lower dopamine levels in striatum, an effect that was reversed by intravenous glucose infusions. Together, our findings suggest that carbohydrate-specific preferences can develop independently of taste quality or caloric load, an effect associated with the ability of a given nutrient to regulate glucose metabolism and stimulate brain dopamine centers.

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Genetic variance contributes to ingestive processes: A survey of 2-deoxy-d-glucose-induced feeding in eleven inbred mouse strains

Cited by 15 publications

References 61 publications

Leptin regulates the reward value of nutrient

Leptin regulates the reward value of nutrient

Regulation of hypothalamic malonyl-CoA by central glucose and leptin

Nutrient Selection in the Absence of Taste Receptor Signaling

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