11 research outputs found
Fasting and High-Fat Diet Alter Histone Deacetylase Expression in the Medial Hypothalamus
Increasing attention is now being given to the epigenetic regulation of animal and human behaviors including the stress response and drug addiction. Epigenetic factors also influence feeding behavior and metabolic phenotypes, such as obesity and insulin sensitivity. In response to fasting and high-fat diets, the medial hypothalamus changes the expression of neuropeptides regulating feeding, metabolism, and reproductive behaviors. Histone deacetylases (HDACs) are involved in the epigenetic control of gene expression and alter behavior in response to a variety of environmental factors. Here, we examined the expression of HDAC family members in the medial hypothalamus of mice in response to either fasting or a high-fat diet. In response to fasting, HDAC3 and β4 expression levels increased while HDAC10 and β11 levels decreased. Four weeks on a high-fat diet resulted in the increased expression of HDAC5 and β8. Moreover, fasting decreased the number of acetylated histone H3- and acetylated histone H4-positive cells in the ventrolateral subdivision of the ventromedial hypothalamus. Therefore, HDACs may be implicated in altered gene expression profiles in the medial hypothalamus under different metabolic states
HDAC immunoreactivities in the medial hypothalamus.
<p>A) HDAC4-immunoreactive cells were found throughout the hypothalamus including the ARH, VMHdm, VMHvl, and DMH of fed mice. B) The PVH of fed mice was immunoreactive for HDAC5. C, D) HDAC8-positive cells were found in the anterior parvicellular and periventricular subdivisions of the PVH of fed (C) and fasting mice (D). E, F) A small number of HDAC10-immunoreactive cells were seen in the DMH (E) and LHA (F). G) Graphs showing the number of HDAC4, β8, and β10 positive cells in the nuclei of the medial hypothalamus. The number of HDAC8-positive cells in the PVH of fasting or high-fat fed mice was significantly larger than that of mice fed a low-fat diet (nβ=β5). Scale bars: 250 Β΅m (A, B); 100 Β΅m (C); 50 Β΅m (E). *P<0.05. ARH: arcuate nucleus, dm: dorsomedial subdivision, DMH: dorsomedial hypothalamic nucleus, LHA: lateral hypothalamic area, PVH: paraventricular nucleus, PVHap: anterior parvicellular subdivion of PVH, PVHpv: periventricular subdivision of PVH, vl: ventrolateral subdivision, VMH: ventromedial hypothalamic nucleus, III: the third ventricle.</p
Expression of <i>HDACs</i> in the medial hypothalamus of fed mice.
<p>The medial hypothalamus of fed mice showed similar expression levels of <i>HDAC1, β2, β3, β4, β5, β6, β7, β8,</i> and <i>β9</i>. The expressions of <i>HDAC10</i> and <i>β11</i> were significantly higher than those of other HDACs. <i>HDAC</i> expression levels (nβ=β10) were normalized using <i>GAPDH</i> (gray bars) or<i>Ξ²-actin</i> expression levels (black bars). Reference gene selection did not affect the measurements of normalized <i>HDAC</i> levels. <i>HDAC</i> expression was also normalized based on the average of all <i>HDAC</i> levels. *P<0.05.</p
Expressions of HDAC4, β5, AcH3, and AcH4s in POMC neurons in the ARH.
<p>A, B, C) HDAC4-positive nuclei were found in POMC-positive cells (arrow in B) and POMC-negative cells (arrowhead in B) in the ARH of a high-fat fed mouse. D, E, F) HDAC5-immunoreactivities were found in the cytoplasm of POMC-positive cells (arrows in E) of a fed mouse. G, H, I) AcH3-positive nuclei were found in POMC-positive cells (arrows in H) of a fed mouse. J, K, L) AcH4-immunoreactivities were found in the nuclei of strongly POMC-positive cells (arrows in K), scattered moderate POMC-positive cells (open arrow in K), and POMC-negative cells (arrowhead in K) of a high-fat fed mouse. Scale bars: 50 Β΅m.</p
Fasting affects the expression of certain HDAC members family in the medial hypothalamus.
<p>After 16-hours of fasting, the expression levels of <i>HDAC3, β4,</i> and <i>Agrp</i> in the medial hypothalamus were increased, and <i>HDAC10</i> and β<i>11</i> levels decreased when compared with levels measured under fed conditions (8β10 mice per group). Data are presented as the expression level relative to the fed condition. *P<0.05.</p
A high-fat diet affects the expression of certain HDAC family members in the medial hypothalamus.
<p>After 4-weeks on a high-fat diet, the expression levels of <i>HDAC5</i> and β<i>8</i> increased when compared to those measured from mice fed a low-fat diet (8β10 mice per group). Data are presented as an expression level relative to the low-fat diet condition. *P<0.05.</p
Fasting decreases the number of acetylated histone-positive cells in the VMHvl.
<p>A) Schematic illustration of the ARH, VMHdm, VMHvl, and DMH (right) and Nissl-stained section (left) of the coronal section of the medial hypothalamus. The third ventricle is in the midline. BβG) Immunoreactive cells for acetylated histone H3 on lysine 14 (AcH3; B, C, D) and acetylated histone H4 on lysine 12 (AcH4; E, F, G) under fed (B, E), fasting (C, F), and high-fat feeing (D, G), were visualized using DAB. The third ventricle is to the left. In mice fed a low-fat diet (B, E) or a high-fat diet (D, G), most cells in the ARH, VMH, and DMH were positive for AcH3 (B, D) and AcH4 (E, G). In fasting mice, a small numbers of cells in the VMHvl were positive for AcH3 (C) and AcH4 (F). H) A graph showing the number of AcH3- and AcH4-positive cells in the ARH, VMHdm, VMHvl, DMH, and LHA. The numbers of AcH3- and AcH4-positive cells in the VMHvl of fasting mice were significantly smaller than those of fed mice (nβ=β6). Scale bar: 250 Β΅m. *P<0.05.</p