mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice

Burke, Luke K.; Darwish, Tamana; Cavanaugh, Althea R.; Virtue, Sam; Roth, Emma; Morro, Joanna; Liu, Shun Mei; Xia, Jing; Dalley, Jeffrey W.; Burling, Keith; Chua, Streamson C.; Vidal-Puig, Toni; Schwartz, Gary J.; Blouet, Clémence

doi:10.7554/elife.22848

Cited by 40 publications

(23 citation statements)

References 69 publications

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“…They are activated upon fasting, inhibited upon refeeding as well as transiently and rapidly inhibited during the sensory perception of food 2 . Here, sensory food perception-dependent regulation of AgRP neurons controls BAT thermogenesis 22 . Interestingly, the ability of sensory food perception to simultaneously activate POMC neurons has been linked to prime liver ER-homeostasis for the postprandial state, in line with the general concept, that melanocortin neurons adapt multiple physiological processes in accordance to anticipated or actual changes in the energy state of the organism 23 .…”

Section: Discussionmentioning

confidence: 99%

NPY mediates the rapid feeding and glucose metabolism regulatory functions of AgRP neurons

Ruud¹,

Pereira²,

Solis³

et al. 2020

Nat Commun

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Activation of Agouti-Related Peptide (AgRP)-expressing neurons promotes feeding and insulin resistance. Here, we examine the contribution of neuropeptide Y (NPY)-dependent signaling to the diverse physiological consequences of activating AgRP neurons. NPYdeficient mice fail to rapidly increase food intake during the first hour of either chemo-or optogenetic activation of AgRP neurons, while the delayed increase in feeding is comparable between control and NPY-deficient mice. Acutely stimulating AgRP neurons fails to induce systemic insulin resistance in NPY-deficient mice, while increased locomotor activity upon AgRP neuron stimulation in the absence of food remains unaffected in these animals. Selective re-expression of NPY in AgRP neurons attenuates the reduced feeding response and reverses the protection from insulin resistance upon optogenetic activation of AgRP neurons in NPY-deficient mice. Collectively, these experiments reveal a pivotal role of NPYdependent signaling in mediating the rapid feeding inducing effect and the acute glucose regulatory function governed by AgRP neurons.

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Section: Discussionmentioning

confidence: 99%

NPY mediates the rapid feeding and glucose metabolism regulatory functions of AgRP neurons

Ruud¹,

Pereira²,

Solis³

et al. 2020

Nat Commun

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show abstract

“…Overexpression of S6K protects high fat feeding induced hyperphagia, fat accumulation and insulin resistance suggesting a critical role of MBH S6K activity in energy homeostasis [ 75 ]. Constitutive activation of mTORC1 signaling in the AgRP neurons modulates sympathetic tone to increase BAT thermogenesis and energy expenditure and protects against diet-induced obesity [ 76 ]. However, a recent study has shown that specific ablation of S6K1 in POMC or AgRP neurons causes no significant change in food intake and body weight.…”

Section: Mtor Signaling In Brainmentioning

confidence: 99%

Role of mTOR in Glucose and Lipid Metabolism

Mao

Zhang

2018

IJMS

211

170

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The mammalian target of rapamycin, mTOR is the master regulator of a cell’s growth and metabolic state in response to nutrients, growth factors and many extracellular cues. Its dysregulation leads to a number of metabolic pathological conditions, including obesity and type 2 diabetes. Here, we review recent findings on the role of mTOR in major metabolic organs, such as adipose tissues, liver, muscle, pancreas and brain. And their potentials as the mTOR related pharmacological targets will be also discussed.

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“…Thus, the signaling molecules of the hypothalamic arcuate nucleus support the search for food, rather than eating (Ammar et al, 2000; Nergårdh et al, 2007; Chen et al, 2015; Dietrich et al, 2015; Burnett et al, 2016). The agouti-related protein neurons of this nucleus can monitor the availability of food in the environment, changing energy utilization from fat to carbohydrate (Chen et al, 2015; Burke et al, 2017; Cavalcanti-de-Albuquerque et al, 2019). Silencing these neurons eliminates the search for food but leaves chewing and swallowing unaffected (Thomas et al, 2018), replicating the effect of dopamine receptor blockade or depletion (Berridge et al, 1989; Bednar et al, 1992; Qian et al, 1998).…”

Section: The Evolutionary Perspectivementioning

confidence: 99%

Eating Behavior and the Evolutionary Perspective on Anorexia Nervosa

et al. 2019

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On the standard perspective, anorexia nervosa and other eating disorders are caused by genetically determined, neurochemically mediated mental illnesses. Standard treatment, cognitive behavioral therapy (CBT), targets cognitive processes thought to maintain the disorders. Effective neurochemically based treatments are not available and the rate of remission is ≤25% 1 year after CBT, with unknown outcomes in the long-term. With starvation as the major threat in biological history, the evolutionary perspective focuses on foraging for food and eating behavior. A neural network, including hypothalamic arcuate peptide-neurons, brainstem serotonin-and dopamine-neurons and their prefrontal cortical projections, mediates (rather than controls) the behavioral adaptations to variations in food availability; activation of the network is associated with opposing behavioral outcomes depending upon external variations. In the clinic, the control of eating behavior is therefore outsourced to a machine that provides feedback on how to eat. Hundreds of eating disorders patients have recovered by practicing eating; the rate of remission is 75% in on average 1 year of treatment, the rate of relapse is 10% over 5 years of follow-up and no patient has died. A two-parameter asymptotic exponential growth curve modeled the eating behavior of 17 healthy women but not that of 17 women with anorexia nervosa. When in remission, the eating behavior of the anorexic women approached that of the healthy women. It is suggested that the treatment of eating disorders should focus on eating behavior.

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mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice

Cited by 40 publications

References 69 publications

NPY mediates the rapid feeding and glucose metabolism regulatory functions of AgRP neurons

NPY mediates the rapid feeding and glucose metabolism regulatory functions of AgRP neurons

Role of mTOR in Glucose and Lipid Metabolism

Eating Behavior and the Evolutionary Perspective on Anorexia Nervosa

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