Diet composition, not calorie intake, rapidly alters intrinsic excitability of hypothalamic AgRP/NPY neurons in mice

Obesity is a chronic condition resulting from a long-term pattern of poor diet and lifestyle. Long-term consumption of high-fat diet (HFD) leads to persistent activation and leptin resistance in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH). Here, for the first time, we demonstrate a...

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Bibliographic Details
Published in:Scientific reports 2015-11, Vol.5 (1), p.16810-16810, Article 16810
Main Authors: Wei, Wei, Pham, Kevin, Gammons, Jesse W, Sutherland, Daniel, Liu, Yanyun, Smith, Alana, Kaczorowski, Catherine C, O'Connell, Kristen M S
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Acute effects
Agouti-Related Protein - genetics
Agouti-Related Protein - metabolism
Animals
Arcuate nucleus
Arcuate Nucleus of Hypothalamus - drug effects
Arcuate Nucleus of Hypothalamus - physiopathology
Body weight
Body weight gain
Chronic illnesses
Diet, High-Fat - adverse effects
Dietary Fats - adverse effects
Energy Intake
Excitability
Firing pattern
Firing rate
Gene Expression Regulation
High fat diet
Hypothalamus
Leptin
Leptin - genetics
Leptin - metabolism
Long-term effects
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Mice, Transgenic
Neurons
Neurons - drug effects
Neuropeptide Y
Neuropeptide Y - genetics
Neuropeptide Y - metabolism
Obesity
Rodents
Signal Transduction
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Summary:Obesity is a chronic condition resulting from a long-term pattern of poor diet and lifestyle. Long-term consumption of high-fat diet (HFD) leads to persistent activation and leptin resistance in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH). Here, for the first time, we demonstrate acute effects of HFD on AgRP neuronal excitability and highlight a critical role for diet composition. In parallel with our earlier finding in obese, long-term HFD mice, we found that even brief HFD feeding results in persistent activation of ARH AgRP neurons. However, unlike long-term HFD-fed mice, AgRP neurons from short-term HFD-fed mice were still leptin-sensitive, indicating that the development of leptin-insensitivity is not a prerequisite for the increased firing rate of AgRP neurons. To distinguish between diet composition, caloric intake, and body weight, we compared acute and long-term effects of HFD and CD in pair-fed mice on AgRP neuronal spiking. HFD consumption in pair-fed mice resulted in a significant increase in AgRP neuronal spiking despite controls for weight gain and caloric intake. Taken together, our results suggest that diet composition may be more important than either calorie intake or body weight for electrically remodeling arcuate AgRP/NPY neurons.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep16810