The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of "brown adipocytes" within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional "brown-like" adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK-dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C -/-mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote "browning" of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology. IntroductionThe cardiac natriuretic peptides (NPs), atrial NP (ANP) and its ventricular companion (BNP), are key hormones in fluid and hemodynamic homeostasis. Their actions are mediated by binding to NP receptor A (NPRA), whose intracellular domain possesses guanylyl cyclase activity to generate the second messenger cGMP (1, 2). Another member of the NP receptor family (NPRC, which is referred to as the clearance receptor) also binds ANP and BNP to remove them from circulation (3). Almost 2 decades ago, NP receptors were unexpectedly found to be expressed in adipose tissue of both rats (4) and humans (5), and, interestingly, levels of NPRC in adipose tissue were found to be sharply decreased by fasting in rats (6). Together, these were some of the first results to suggest that perhaps cardiac NPs have a metabolic role in adipocytes, including a putative role for adipose tissue in the clearance of these peptides from the circulation (7).ANP was subsequently shown to increase lipolysis in human adipocytes, with a potency similar to that of catecholamines (8), which are the well-established physiological pathway controlling lipolysis through activation of the β-adrenergic receptors (β-ARs). Interestingly, the ability of NPs to stimulate lipolysis was reported to be primate specific and apparently absent from rodent adipose tissue (9). To understand this process mechanistically, recall that β-ARs, as the classic stimulator o...

This study confirmed the validity of the CIRS as an indicator of health status and demonstrated its ability to predict 18-month mortality and rehospitalization in hospitalized elderly patients. The availability of detailed guidelines for scoring the CIRS can improve its usefulness and facilitate more-widespread use for research and clinical aims.

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The elderly are an ever increasing population in overcrowded emergency departments (EDs) in many countries. They have multiple health problems and consume more time and resources than younger patients. They are more frequently admitted and experience adverse outcomes after they are discharged from the ED. These frail patients could require specific skills, instruments and organisational models of emergency care in order to look after their complex needs. As such, several approaches have been tried and tested to improve emergency care for them. This article analyses the epidemiological load and problems faced when confronted with elder ED patients. We critically review organisational models, clinical approaches and methodologies in order to reduce ED physicians' difficulties and to improve quality of care and outcomes for elder patients. Triage, clinical assessment and discharge are identified as critical moments during an emergency care process, and interesting and useful instruments are proposed as possible solutions.