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Ablation of AgRP neurons impairs adaption to restricted feeding.

Tan K, Knight ZA, Friedman JM - Mol Metab (2014)

Bottom Line: We found that the activity of AgRP/NPY neurons changed rhythmically during RF suggesting that these neurons are a component of the FEO.However, ablated animals showed 30% mortality within 4 days of RF.These findings identify AgRP/NPY neurons as a key cellular component of the food-entrained oscillator.

View Article: PubMed Central - PubMed

Affiliation: The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.

ABSTRACT
While the SCN controls the circadian clock, further evidence suggests the existence of a food-entrainable oscillator (FEO) that links behavior to changes in food availability such as during restricted feeding (RF). We found that the activity of AgRP/NPY neurons changed rhythmically during RF suggesting that these neurons are a component of the FEO. We next ablated AgRP/NPY neurons in neonates with diphtheria toxin resulting in the loss of ∼50% of AgRP/NPY neurons. Body weight and food intake were unchanged in adult animals after neonatal ablation, as were the responses to leptin treatment, leptin withdrawal, food deprivation and ghrelin treatment. However, ablated animals showed 30% mortality within 4 days of RF. Moreover, the recovery of body weight and food intake in surviving animals lagged behind controls with an absence of food anticipatory activity even after three days. These findings identify AgRP/NPY neurons as a key cellular component of the food-entrained oscillator.

No MeSH data available.


Related in: MedlinePlus

Response of AgRP DTR animals to overnight fast. (A–F) Overnight deprivation of food induced expression of cfos was mainly localized to AgRP neurons. (G–I) cfos immunostaining in the arcuate nucleus after overnight fast in control vs. AgRP DTR animals (DTR 67.75 ± 11.12 vs AgRP 30.33 ± 5.364, p < 0.05). n = 4 in each group (J) Food intake of DTR and AgRP DTR animals after overnight fast. n ≥ 10 in each group. Scale bar = 50 μm.
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fig4: Response of AgRP DTR animals to overnight fast. (A–F) Overnight deprivation of food induced expression of cfos was mainly localized to AgRP neurons. (G–I) cfos immunostaining in the arcuate nucleus after overnight fast in control vs. AgRP DTR animals (DTR 67.75 ± 11.12 vs AgRP 30.33 ± 5.364, p < 0.05). n = 4 in each group (J) Food intake of DTR and AgRP DTR animals after overnight fast. n ≥ 10 in each group. Scale bar = 50 μm.

Mentions: AgRP neurons become activated when animals are food restricted (Figure 4A–F) so we next assayed the response of AgRP DTR animals to a 24 h fast. We first assayed cfos expression in these neurons after food restriction and found that there were significantly fewer cfos positive cells in the arcuate nucleus of AgRP DTR animals compared to controls (Figure 4G–I). Note the reduction in the number of cells expressing cfos was consistent with the loss of AGRP neurons suggesting that the cfos response in surviving cells was unchanged. Despite of the loss of AgRP neurons and the similarly low number of cfos positive cells in AgRP DTR animals, the food intake of these animals after an 18 h fast was unaltered compared to controls (Figure 4J).


Ablation of AgRP neurons impairs adaption to restricted feeding.

Tan K, Knight ZA, Friedman JM - Mol Metab (2014)

Response of AgRP DTR animals to overnight fast. (A–F) Overnight deprivation of food induced expression of cfos was mainly localized to AgRP neurons. (G–I) cfos immunostaining in the arcuate nucleus after overnight fast in control vs. AgRP DTR animals (DTR 67.75 ± 11.12 vs AgRP 30.33 ± 5.364, p < 0.05). n = 4 in each group (J) Food intake of DTR and AgRP DTR animals after overnight fast. n ≥ 10 in each group. Scale bar = 50 μm.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4209355&req=5

fig4: Response of AgRP DTR animals to overnight fast. (A–F) Overnight deprivation of food induced expression of cfos was mainly localized to AgRP neurons. (G–I) cfos immunostaining in the arcuate nucleus after overnight fast in control vs. AgRP DTR animals (DTR 67.75 ± 11.12 vs AgRP 30.33 ± 5.364, p < 0.05). n = 4 in each group (J) Food intake of DTR and AgRP DTR animals after overnight fast. n ≥ 10 in each group. Scale bar = 50 μm.
Mentions: AgRP neurons become activated when animals are food restricted (Figure 4A–F) so we next assayed the response of AgRP DTR animals to a 24 h fast. We first assayed cfos expression in these neurons after food restriction and found that there were significantly fewer cfos positive cells in the arcuate nucleus of AgRP DTR animals compared to controls (Figure 4G–I). Note the reduction in the number of cells expressing cfos was consistent with the loss of AGRP neurons suggesting that the cfos response in surviving cells was unchanged. Despite of the loss of AgRP neurons and the similarly low number of cfos positive cells in AgRP DTR animals, the food intake of these animals after an 18 h fast was unaltered compared to controls (Figure 4J).

Bottom Line: We found that the activity of AgRP/NPY neurons changed rhythmically during RF suggesting that these neurons are a component of the FEO.However, ablated animals showed 30% mortality within 4 days of RF.These findings identify AgRP/NPY neurons as a key cellular component of the food-entrained oscillator.

View Article: PubMed Central - PubMed

Affiliation: The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.

ABSTRACT
While the SCN controls the circadian clock, further evidence suggests the existence of a food-entrainable oscillator (FEO) that links behavior to changes in food availability such as during restricted feeding (RF). We found that the activity of AgRP/NPY neurons changed rhythmically during RF suggesting that these neurons are a component of the FEO. We next ablated AgRP/NPY neurons in neonates with diphtheria toxin resulting in the loss of ∼50% of AgRP/NPY neurons. Body weight and food intake were unchanged in adult animals after neonatal ablation, as were the responses to leptin treatment, leptin withdrawal, food deprivation and ghrelin treatment. However, ablated animals showed 30% mortality within 4 days of RF. Moreover, the recovery of body weight and food intake in surviving animals lagged behind controls with an absence of food anticipatory activity even after three days. These findings identify AgRP/NPY neurons as a key cellular component of the food-entrained oscillator.

No MeSH data available.


Related in: MedlinePlus