Hypothalamic mTOR Signaling Regulates Food Intake

Cota, Daniela; Proulx, Karine; Smith, Kenneth V.; Kozma, Sara C.; Thomas, George; Woods, Stephen C.; Seeley, Randy J.

doi:10.1126/science.1124147

Cited by 1,136 publications

(1,194 citation statements)

References 26 publications

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“…Injection of L-Leu, but not of L-Val, in the third ventricle of the brain activated the mammalian target of rapamycin and resulted in a decrease in feed intake (Cota et al, 2006). These observations suggest that there is a specific mechanism that is sensitive to brain Leu concentration that regulates feed intake.…”

Section: Discussionmentioning

confidence: 88%

Response of piglets to the valine content in diet in combination with the supply of other branched-chain amino acids

Gloaguen

Floc'H

Brossard

et al. 2011

Animal

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The branched-chain amino acids (BCAA) valine (Val) and isoleucine (Ile) are considered to be among the next-limiting amino acids for growth in piglets. In earlier studies, we estimated the standardized ileal digestible (SID) Val : Lys (lysine) requirement to be at least 70%, whereas the Ile : Lys requirement may be as low as 50%. Because the BCAA partially share a common route of catabolism, the supply of one BCAA may affect the availability of the other BCAA. Four experiments were conducted to determine the response of 6-week-old piglets to the Val supply in relation to the other BCAA. A deficient supply of Val or Ile typically results in a reduction in average daily feed intake (ADFI). Experiment 1 was designed to determine the effect of a limiting Val supply, independent of the effect on feed intake. In a dose-response study using restrictively fed piglets, nitrogen retention did not increase for an SID Val : Lys supply greater than 64%. In the remaining experiments, piglets were offered feed ad libitum using ADFI, average daily gain (ADG) and gain-to-feed ratio as response criteria. The interaction between the Val and leucine (Leu) was studied in Experiment 2 in a 2 3 2 factorial design (60% and 70% SID Val : Lys, and 111% and 165% SID Leu : Lys). Performance was considerably lower in piglets receiving 60% Val : Lys compared with those receiving 70% Val : Lys and was lowest in piglets receiving the diet with low Val and high Leu content. To further evaluate the interaction between Val and Leu, a dose-response study was carried out in which the response to Val supply was studied in combination with high Leu supply (165% Leu : Lys). Using a curvilinear-plateau model, the average SID Val : Lys requirement was 72%. However, low Val supply (60% SID Val : Lys) reduced performance by 13% to 38%, which was much greater than what we observed in earlier studies. Experiment 4 was carried out to test the hypothesis that the Val requirement is not affected by low Ile supply (50% SID Ile : Lys). Performance was not improved for Val : Lys supplies greater than 65%, which may indicate that Ile (and not Lys) was second-limiting in this study. In conclusion, the first response of piglets to deficient Val supply appears to be a reduction in ADFI, rather than a reduction in ADG or nitrogen retention. A large supply of Leu may not affect the Val requirement per se, but may aggravate the consequences of Val deficiency.

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Section: Discussionmentioning

confidence: 88%

Response of piglets to the valine content in diet in combination with the supply of other branched-chain amino acids

Gloaguen

Floc'H

Brossard

et al. 2011

Animal

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“…Our results show that growth of C4-2 tumor cells in the bone results in decreased body weight of tumor-bearing animals, and that treatment with RAD001 results in maintenance of body weight and lean body mass. The Akt/mTOR pathway has been shown to play a role in anorexia, including, possibly, tumor-related cachexia [42]. Leptin and leucin stimulate hypothalamic mTOR and decrease food intake and body weight in rats.…”

Section: Discussionmentioning

confidence: 99%

RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid

et al. 2008

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“…In the same vein, we have recently obtained evidence that brain signaling through sensors of the intracellular energy state, such as the mammalian target of rapamycin (mTOR) and AMP kinase (AMPK), is likely to play a crucial role in the central control of puberty onset, eventually via modulation of Kiss1 gene expression at the hypothalamus, as we have preliminarily observed at least for mTOR signaling (unpublished data). Of note, both mTOR and AMPK have been proposed as transducer of leptin effects in terms of energy homeostasis [47]. Altogether, these observations disclose an additional level of complexity in the metabolic regulation of hypothalamic KISS1 system, whereby a set of intracellular sensors and transcriptional factors are likely to cooperate in order to mediate the effects of extracellular signals (e.g., leptin) on the expression of KISS1 gene.…”

Section: Molecular Mechanisms For the Metabolic Regulation Of Hypothamentioning

confidence: 92%

Kisspeptin signaling in the brain: Recent developments and future challenges

Tena‐Sempere

2010

Molecular and Cellular Endocrinology

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Kisspeptins, a family of peptides encoded by the KISS1 gene which binds GPR54 (or KISS1 receptor), have recently emerged as essential neuropeptide regulators of key aspects of reproductive maturation and function, including puberty onset, neuroendocrine control of ovulation and metabolic regulation of fertility. Yet, while the neuroanatomy of kisspeptin system has begun to be deciphered, and the involvement of kisspeptins in the above phenomena has been experimentally documented in recent years, precise information on the signaling events underlying these functions has remained scarce. Similarly, the nature and mechanisms of action of most of the regulatory signals of KISS1 expression in the brain are largely unknown. In this review, we will comprehensively summarize some of the recent developments in these areas of kisspeptin physiology, with the ultimate aim to delineate unresolved questions and future pathways for the progression of this active field of Neuroendocrinology.

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Hypothalamic mTOR Signaling Regulates Food Intake

Cited by 1,136 publications

References 26 publications

Response of piglets to the valine content in diet in combination with the supply of other branched-chain amino acids

Response of piglets to the valine content in diet in combination with the supply of other branched-chain amino acids

RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid

Kisspeptin signaling in the brain: Recent developments and future challenges

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