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 −4 expression levels increased while HDAC10 and −11 levels decreased. Four weeks on a high-fat diet resulted in the increased expression of HDAC5 and −8. 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

Ablation of NG2 Proteoglycan Leads to Deficits in Brown Fat Function and to Adult Onset Obesity

Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2-dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O2 consumption and CO2 production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator (PGC)1-α, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre-adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes

Cervical myelopathy caused by soft-tissue mass in diffuse idiopathic skeletal hyperostosis

A rare case of cervical spinal cord compression in diffuse idiopathic skeletal hyperostosis (DISH or Forestier’s Disease) caused by a craniocervical mass of soft-tissue is reported. The objective is to describe an uncommon mechanism of spinal cord compression in DISH. Three weeks after a cardiac infarction a 69-year-old man slowly developed spastic tetraparesis. Magnetic resonance tomography showed a craniocervical tumor compressing the spinal cord and a massive DISH of the cervical spine. An extended mass of yellowish amorphous material was removed from between the dura, the posterior odontoid process and the posterior aspect of vertebral body C2 reaching to the upper part of C3.The histologic appearance indicated connective tissue and cell-degenerated cartilaginous tissue. There was no inflammatory component and no evidence of neoplasia. No ossification of the posterior longitudinal ligament (OPLL) was found. After removal and craniocervical stabilization the patient’s neurologic function improved remarkably. The increase of mechanical stress on the atlantoaxial segment and enhanced proliferation reaction of the connective tissue in DISH are suggested as the underlying pathomechanisms in the formation of this soft-tissue mass

Simultaneous ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum causing upper thoracic myelopathy in DISH: case report and literature review

A rare case of a 44-year-old Chinese male with diffuse idiopathic skeletal hyperostosis (DISH) and simultaneous ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) at T1–2 causing thoracic myelopathy is reported herein. Posterior decompression without extirpating the OPLL was performed at T1–2. Postoperatively, symptoms were greatly improved, with remaining hyperreflexia and Grade 4/5 muscle strength in the lower extremities. The Japanese Orthopedic Association score improved from 5 preoperatively to 9 at final follow-up. The presence of a cyst due to leakage of cerebrospinal fluid was confirmed by MRI at day 27, but it resolved after conservative management. The clinical manifestation of DISH, the relationship among DISH, OPLL, and OLF, and management of thoracic myelopathy due to OPLL and OLF were reviewed