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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 ghrelin. (A–F) cfos expression in the arcuate nucleus was mainly colocalized to AgRp neurons after ghrelin injection. (G–I) cfos immunostaining in the arcuate nucleus after ghrelin injection in DTR vs. AgRP DTR animals (DTR 137.5 ± 15.39 vs AgRP DTR 23.33 ± 5.365, p < 0.01). n = 4 in each group (J) Food intake of DTR and AgRP DTR animals after either PBS or ghrelin injection. n ≥ 8 in each group. Scale bar = 50 μm.
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fig5: Response of AgRP DTR animals to ghrelin. (A–F) cfos expression in the arcuate nucleus was mainly colocalized to AgRp neurons after ghrelin injection. (G–I) cfos immunostaining in the arcuate nucleus after ghrelin injection in DTR vs. AgRP DTR animals (DTR 137.5 ± 15.39 vs AgRP DTR 23.33 ± 5.365, p < 0.01). n = 4 in each group (J) Food intake of DTR and AgRP DTR animals after either PBS or ghrelin injection. n ≥ 8 in each group. Scale bar = 50 μm.

Mentions: Because AgRP neurons also express the ghrelin receptor (Ghsr), we also assayed the response of AgRP DTR animals to ghrelin. We found that most of the cfos immunoreactivity in the arcuate nucleus colocalized with AgRP and NPY (Figure 5A–F). Similar to the case for food restriction, ghrelin injection during the light phase resulted in much a smaller number of cfos positive cells in the arcuate of AgRP DTR animals (Figure 5G–I). However, despite the decreased number of cfos positive cells, the food intake of AGRP DTR animals after ghrelin treatment was indistinguishable from that of control animals (Figure 5J). Taken together, these results show that animals with AgRP ablation do not show alterations of baseline food intake and weight and that their responses to leptin treatment, leptin withdrawal, fasting and ghrelin treatment are all normal.


Ablation of AgRP neurons impairs adaption to restricted feeding.

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

Response of AgRP DTR animals to ghrelin. (A–F) cfos expression in the arcuate nucleus was mainly colocalized to AgRp neurons after ghrelin injection. (G–I) cfos immunostaining in the arcuate nucleus after ghrelin injection in DTR vs. AgRP DTR animals (DTR 137.5 ± 15.39 vs AgRP DTR 23.33 ± 5.365, p < 0.01). n = 4 in each group (J) Food intake of DTR and AgRP DTR animals after either PBS or ghrelin injection. n ≥ 8 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

fig5: Response of AgRP DTR animals to ghrelin. (A–F) cfos expression in the arcuate nucleus was mainly colocalized to AgRp neurons after ghrelin injection. (G–I) cfos immunostaining in the arcuate nucleus after ghrelin injection in DTR vs. AgRP DTR animals (DTR 137.5 ± 15.39 vs AgRP DTR 23.33 ± 5.365, p < 0.01). n = 4 in each group (J) Food intake of DTR and AgRP DTR animals after either PBS or ghrelin injection. n ≥ 8 in each group. Scale bar = 50 μm.
Mentions: Because AgRP neurons also express the ghrelin receptor (Ghsr), we also assayed the response of AgRP DTR animals to ghrelin. We found that most of the cfos immunoreactivity in the arcuate nucleus colocalized with AgRP and NPY (Figure 5A–F). Similar to the case for food restriction, ghrelin injection during the light phase resulted in much a smaller number of cfos positive cells in the arcuate of AgRP DTR animals (Figure 5G–I). However, despite the decreased number of cfos positive cells, the food intake of AGRP DTR animals after ghrelin treatment was indistinguishable from that of control animals (Figure 5J). Taken together, these results show that animals with AgRP ablation do not show alterations of baseline food intake and weight and that their responses to leptin treatment, leptin withdrawal, fasting and ghrelin treatment are all normal.

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