Altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy.

Monocarboxylate transporter 1 (MCT1) facilitates the transport of monocarboxylate fuels (lactate, pyruvate and ketone bodies) and acidic drugs, such as valproic acid, across cell membranes. We recently reported that MCT1 is deficient on microvessels in the epileptogenic hippocampal formation in patients with medication-refractory temporal lobe epilepsy (TLE). To further define the role of MCT1 in the pathophysiology of TLE, we used immunohistochemistry and stereological analysis to localize and quantify the transporter in the hippocampal formation in three novel and highly relevant rat models of TLE and in nonepileptic control animals. One model utilizes methionine sulfoximine to induce brain glutamine synthetase deficiency and recurrent limbic seizures, while two models employ an episode of perforant pathway stimulation to cause epilepsy. MCT1 was lost on microvessels and upregulated on astrocytes in the hippocampal formation in all models of TLE. Notably, the loss of MCT1 on microvessels was not due to a reduction in microvessel density. The similarities in MCT1 expression among human subjects with TLE and several animal models of the disease strongly suggest a critical role of this molecule in the pathogenesis of TLE. We hypothesize that the downregulation of MCT1 may promote seizures via impaired uptake of ketone bodies and antiepileptic drugs by the epileptogenic brain. We also propose that the overexpression of MCT1 on astrocytes may lead to increased uptake or release of monocarboxylates by these cells, with important implications for brain metabolism and excitability. These hypotheses can now be rigorously tested in several animal models that replicate key features of human TLE.

Adiponectin is independently associated with apolipoprotein B to A-1 ratio in Koreans.

Apolipoprotein B to A-1 (apo B/A-1) ratio is reportedly a better predictor of atherosclerotic vascular disease than low-density lipoprotein cholesterol (LDL-C). The aim of this study was to assess the association of serum apo B/A-1 ratio with insulin resistance and adiponectin in patients with different grades of glucose intolerance. Patients were divided according to glucose tolerance into 3 groups: normal glucose tolerance without metabolic syndrome (n = 229), impaired fasting glucose (subjects with fasting plasma glucose level between 100 and 125 mg/dL, n = 658), and type 2 diabetes mellitus (n = 381). Serum concentrations of apo B, apo A-1, glucose, total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDL-C) and adiponectin were measured. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance index (HOMA-IR). There were significant differences in metabolic parameters among the groups, including waist circumference, insulin, HOMA-IR, and apo B/A-1 ratio, which increased sequentially with glucose intolerance, whereas adiponectin level decreased with increasing severity of glucose intolerance. The apo B/A-1 ratio was significantly correlated with TC, triglycerides, LDL-C, HDL-C, adiponectin, and HOMA-IR in normal glucose tolerance, impaired fasting glucose, and type 2 diabetes mellitus. Multiple regression analysis showed that apo B/A-1 ratio was significantly associated with TC, LDL-C, HDL-C, and adiponectin. In conclusion, apo B/A-1 ratio was significantly associated with insulin resistance according to glucose intolerance; and serum adiponectin was an important independent factor associated with apo B/A-1 ratio in Koreans.