This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity. Material and Methods: Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos, a neural activator. The distributional relationships of SGLT-2 and c-Fos were examined by immunofluorescence. Results: Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin. Conclusion: This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function.

Background: Obesity and hyperuricemia mutually influence metabolic syndrome. This study discusses the metabolic relationships between obesity and hyperuricemia in terms of pathophysiology, complications, and treatments. Methods: We searched for preclinical or clinical studies on the pathophysiology, complications, and therapy of obesity and hyperuricemia on the PubMed database. Results: In this systemic review, we summarized our searching results on topics of pathophysiology, complications and therapeutic strategy. In pathophysiology, we firstly introduce genetic variations for obesity, hyperuricemia and their relationships by genetic studies. Secondly, we talk about the epigenetic influences on obesity and hyperuricemia. Thirdly, we describe the central metabolic regulation and the role of hyperuricemia. Then, we refer to the character of adipose tissue inflammation and oxidative stress in the obesity and hyperuricemia. In the last part of this topic, we reviewed the critical links of gut microbiota in the obesity and hyperuricemia. In the following part, we review the pathophysiology of major complications in obesity and hyperuricemia including insulin resistance and type 2 diabetes mellitus, chronic kidney disease, cardiovascular diseases, and cancers. Finally, we recapitulate the therapeutic strategies especially the novel pharmaceutic interventions for obesity and hyperuricemia, which concurrently show the mutual metabolic influences between two diseases. Conclusion: The data reviewed here delineate the metabolic relationships between obesity and hyperuricemia, and provide a comprehensive overview of the therapeutic targets for the management of metabolic syndromes.

Splenomegaly with sea-blue histiocytes is not associated with dyslipidemia, except in severe cases of hypertriglyceridemia, Tangier disease, or lecithin cholesterol acyltransferase deficiency. We describe two kindreds in which the sea-blue histiocyte syndrome was associated with an apoE variant in the absence of severe dyslipidemia. Both patients presented with mild hypertriglyceridemia and splenomegaly. After splenectomy both patients developed severe hypertriglyceridemia. Pathological evaluation of the spleen revealed the presence of sea-blue histiocytes. A mutation of apoE was demonstrated, with a 3-bp deletion resulting in the loss of a leucine at position 149 in the receptor-binding region of the apoE molecule [apoE (delta149 Leu)]. Although both probands were unrelated, they were of French Canadian ancestry, suggesting the possibility of a founder effect. In summary, we describe two unrelated probands with primary sea-blue histiocytosis who had normal or mildly elevated serum triglyceride concentrations that markedly increased after splenectomy. In addition, we provide evidence linking the syndrome to an inherited dominant mutation in the apoE gene, a 3-bp deletion on the background of an apoE 3 allele that causes a derangement in lipid metabolism and leads to splenomegaly in the absence of severe hypertriglyceridemia.

Objective: We aimed to evaluate the relationship between thyroid-stimulating hormone (TSH) and bone mineral density (BMD) in euthyroid type 2 diabetes (T2D). Methods: This retrospective analysis enrolled 439 T2D patients with normal thyroid function, including 226 males and 213 females. All the female patients were postmenopausal. Serum glycosylated hemoglobin A1c (HbA1c), TSH, free triiodothyronine (FT 3 ), and free thyroxine (FT 4 ) concentrations were analyzed. BMD of the lumbar spine (L 1 -L 4 ), femoral neck, and hip joint was determined using dual-energy X-ray absorptiometry. Results: The patients were grouped based on tri-sectional quantiles of the TSH levels: 0.55~1.70mIU/L (Group 1), 1.71~2.58mIU/L (Group 2), and 2.59~4.74mIU/L (Group 3). Our data showed that, in male patients, no difference in BMD was identified among groups. In postmenopausal women, unlike at the lumbar spine (P = 0.459), the mean BMD at the femoral neck (P = 0.014) and hip joint (P = 0.014) had a statistical difference among groups and increased with TSH level. In addition, our analysis demonstrated that TSH levels shown no correlation with BMD at all sites in males. However, in females, BMD at the femoral neck (r = 0.156, P = 0.023) and hip joint (r = 0.172, P = 0.012) had a positive correlation with TSH levels. After adjusting for age and BMI, multiple regression analysis showed that TSH levels influenced BMD at the femoral neck (β = 0.188, P = 0.001) and hip joint (β = 0.204, P = 0.001) in female patients. Conclusion:In summary, our data demonstrates that low TSH levels are associated with decreased BMD at the femoral neck and hip joint in postmenopausal T2D women with euthyroidism.