PT  - JOURNAL ARTICLE
AU  - Tariq Zaman
AU  - Xun Zhou
AU  - Nihar R. Pandey
AU  - Zhaohong Qin
AU  - Kianoosh Keyhanian
AU  - Kendall Wen
AU  - Ryan D. Courtney
AU  - Alexandre F.R. Stewart
AU  - Hsiao-Huei Chen
TI  - LMO4 Is Essential for Paraventricular Hypothalamic Neuronal Activity and Calcium Channel Expression to Prevent Hyperphagia
AID  - 10.1523/JNEUROSCI.3419-13.2014
DP  - 2014 Jan 01
TA  - The Journal of Neuroscience
PG  - 140--148
VI  - 34
IP  - 1
4099  - http://www.jneurosci.org/content/34/1/140.short
4100  - http://www.jneurosci.org/content/34/1/140.full
SO  - J. Neurosci.2014 Jan 01; 34
AB  - The dramatic increase in the prevalence of obesity reflects a lack of progress in combating one of the most serious health problems of this century. Recent studies have improved our understanding of the appetitive network by focusing on the paraventricular hypothalamus (PVH), a key region responsible for the homeostatic balance of food intake. Here we show that mice with PVH-specific ablation of LIM domain only 4 (Lmo4) become rapidly obese when fed regular chow due to hyperphagia rather than to reduced energy expenditure. Brain slice recording of LMO4-deficient PVH neurons showed reduced basal cellular excitability together with reduced voltage-activated Ca2+ currents. Real-time PCR quantification revealed that LMO4 regulates the expression of Ca2+ channels (Cacna1h, Cacna1e) that underlie neuronal excitability. By increasing neuronal activity using designer receptors exclusively activated by designer drugs technology, we could suppress food intake of PVH-specific LMO4-deficient mice. Together, these results demonstrate that reduced neural activity in LMO4-deficient PVH neurons accounts for hyperphagia. Thus, maintaining PVH activity is important to prevent hyperphagia-induced obesity.