Ectopic fat deposition and global cardiometabolic risk : New paradigm in cardiovascular medicine

The obesity epidemic is a global public health concern that increases the likelihood of morbidity and mortality of metabolic and cardiovascular disease (CVD) and threatens to reduce life expectancy around the world. The concept of the metabolic syndrome (MetS) takes into account that visceral fat plays an essential role in the development of metabolic and cardiovascular diseases. However, MetS cannot be used to assess global CVD risk but is at best one more modifiable CVD risk factor. Thus, global cardiometabolic risk (the global risk of cardiovascular disease resulting from traditional risk factors combined with the additional contribution of the metabolic syndrome and/or insulin resistance) should be considered individually. There is solid evidence supporting the notion that excess abdominal fat is predictive of insulin resistance and the presence of related metabolic abnormalities currently referred to as MetS. Despite the fact that abdominal obesity is a highly prevalent feature of MetS, the mechanisms by which abdominal obesity is causally related to MetS are not fully elucidated. Besides visceral fat accumulation, ectopic lipid deposition, especially in liver and skeletal muscle, has been implicated in the pathophysiology of diabetes, insulin resistance and obesity-related disorders. Also, ectopic fat deposition could be deteriorated in the heart components such as (1) circulatory and locally recruited fat, (2) intra- and extra-myocellular fat, (3) perivascular fat, and (4) pericardial fat. In this review, the contribution of ectopic lipid deposition to global cardiometabolic risk is reviewed and also discussed are potential underlying mechanisms including adipocytokine, insulin resistance and lipotoxicity

イショセイ シボウ ト 2ガタ トウニョウビョウ シンゾウ ケッカンビョウ

There is evidence supporting the notion that excess abdominal fat is predictive of insulin resistance and the presence of related metabolic abnormalities currently referred to as the metabolic syndrome (MetS). Despite the fact that abdominal obesity is a highly prevalent feature of MetS, the mechanisms by which abdominal obesity is causally related to MetS are not fully elucidated. Besides visceral fat accumulation, ectopic lipid deposition, especially in the liver and skeletal muscle, has been implicated in the pathophysiology of diabetes, insulin resistance and obesity-related disorders. In addition, ectopic fat deposition play a critical role in the heart components such as (1) circulatory and locally recruited fat, (2) intra-and extra-myocellular fat, (3) perivascular fat, and (4) pericardial fat. In this review, the contribution of ectopic lipid deposition to global cardiometabolic risk is discussed via possible mechanisms including adipocytokine, insulin resistance and lipotoxicity

Two cases of low back pain of unknown etiology diagnosed as multiple myeloma

We report two cases of patients complaining of lumbar back pain of unknown etiology which were finally diagnosed as multiple myeloma. The first case was a woman in her 80s with a chief complaint of lumbar back pain. The second case was a male in his 70s. He also consulted our institution because his pain did not subside despite receiving increased doses of oral medication and nerve blocks from his previous doctor. Both patients presented with compression fractures on plain radiography, and additionally with cytopenia, hyperproteinemia, and hypoalbuminemia in blood tests. Further tests were conducted due to suspected multiple myeloma, revealing a punched-out legion in the skull and elevated levels of β2 microglobulin and Immunoglobulin G. Subsequently, both patients were transferred to the hematology department. In these two cases, we had predicted the presence of multiple myeloma from the results of initial testing and subsequently successfully provided definitive diagnoses following additional examinations

Micro-DC rotary-motor working smoothly with neither contact brush nor fixed-axis

Successful construction of a simple sub-millimeter micromotor is reported, which operates under stationary direct current (DC) voltage, with neither a fixed rotational axis nor contacting brush. The screw-shaped chiral rotor undergoes a spinning motion when stationary DC voltage is applied using a pair of cone-shaped electrodes with a staggered arrangement. Analysis of the fluid motion revealed the occurrence of inward-swirling flow in between the electrode tips, which generates a stable spinning motion under the DC voltage. This simple DC micromotor could be beneficial for the advancement of microfluidics, microrobots, etc

Disease Outcome and Brain Metabolomics of Cyclophilin-D Knockout Mice in Sepsis

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction resulting from a systemic inflammatory response to infection, but the mechanism remains unclear. The mitochondrial permeability transition pore (MPTP) could play a central role in the neuronal dysfunction, induction of apoptosis, and cell death in SAE. The mitochondrial isomerase cyclophilin D (CypD) is known to control the sensitivity of MPTP induction. We, therefore, established a cecal ligation and puncture (CLP) model, which is the gold standard in sepsis research, using CypD knockout (CypD KO) mice, and analyzed the disease phenotype and the possible molecular mechanism of SAE through metabolomic analyses of brain tissue. A comparison of adult, male wild-type, and CypD KO mice demonstrated statistically significant differences in body temperature, mortality, and histological changes. In the metabolomic analysis, the main finding was the maintenance of reduced glutathione (GSH) levels and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the KO animals following CLP. In conclusion, we demonstrate that CypD is implicated in the pathogenesis of SAE, possibly related to the inhibition of MPTP induction and, as a consequence, the decreased production of ROS and other free radicals, thereby protecting mitochondrial and cellular function

MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism.

AIMS: Mechanisms regulating adiponectin expression have not been fully clarified. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are involved in biological processes, including obesity and insulin resistance. We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression. METHODS AND RESULTS: First, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3'-UTR binding site. Addition of tumor necrosis factor-α (TNFα) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r = -0.624, p = 0.004). CONCLUSIONS: We found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence-binding site. Our findings warrant further investigations into the role of miRNAs in regulating the adiponectin expression