Fsp27 is a lipid droplet-associated protein almost exclusively expressed in adipocytes where it facilitates unilocular lipid droplet formation. In mice, Fsp27 deficiency is associated with increased basal lipolysis, ‘browning’ of white fat and a healthy metabolic profile, whereas a patient with congenital CIDEC deficiency manifested an adverse lipodystrophic phenotype. Here we reconcile these data by showing that exposing Fsp27-null mice to a substantial energetic stress by crossing them with ob/ob mice or BATless mice, or feeding them a high-fat diet, results in hepatic steatosis and insulin resistance. We also observe a striking reduction in adipose inflammation and increase in adiponectin levels in all three models. This appears to reflect reduced activation of the inflammasome and less adipocyte death. These findings highlight the importance of Fsp27 in facilitating optimal energy storage in adipocytes and represent a rare example where adipose inflammation and hepatic insulin resistance are disassociated.
Obesity is characterized by excessive accumulation of lipid metabolites in adipose tissues as well as in nonadipose tissues, such as liver, muscle, and pancreas ( 1 ). Because obesity is considered as a major risk factor for most metabolic diseases, including hyperlipidemia, hypercholesterolemia, type 2 diabetes, hypertension, and cardiovascular disease ( 2-4 ), numerous investigations have been conducted to elucidate the key components in energy homeostasis, which is crucial to develop therapeutic agents for obesity and obesity-associated metabolic disorders.AMP-activated protein kinase (AMPK) is a master energy sensor that integrates nutrients, hormones, and stress signals to maintain whole-body energy homeostasis ( 5, 6 ). Under various stress conditions, AMPK is activated by allosteric stimulation in response to an increased AMP/ATP ratio or mitochondria activity change. AMPK activation also is induced by upstream stress kinases, such as liver kinase B1 (LKB1) or calcium/calmodulin-dependent protein kinase kinase (CaMKK) ( 7-10 ). Activated AMPK is involved in the regulation of diverse metabolic pathways.
Effective modulus of elasticity Finite-element analysis Ligament efficiency Natural frequency Perforated plate RayleigheRitz method Square plate a b s t r a c t In this study, the natural frequencies of the perforated square plate with a square penetration pattern are obtained as a function of ligament efficiency using the commercial finite-element analysis code ANSYS. In addition, they are used to extract the effective modulus of elasticity under an assumption of a constant Poisson's ratio. The effective modulus of elasticity of the fully perforated square plate is applied to the modal analysis of a partially perforated square plate using a homogeneous finite-element analysis model.The natural frequencies and the corresponding mode shapes of the homogeneous model are compared with the results of the detailed finite-element analysis model of the partially perforated square plate to check the validity of the effective modulus of elasticity. In addition, the theoretical method to calculate the natural frequencies of a partially perforated square plate with fixed edges is suggested according to the RayleigheRitz method.
This is the first study demonstrating that ACE shedding is regulated by NQO1 activation, which is possibly correlated with relieving hypertension in SHR. These findings provide strong evidence suggesting that NQO1 might be a new target for ACE modulation and BP control.
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