Obesity is an epidemic in Western society, and causes rapidly accelerating rates of type 2 diabetes and cardiovascular disease. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a 'fuel gauge' to monitor cellular energy status. We investigated the potential role of AMPK in the hypothalamus in the regulation of food intake. Here we report that AMPK activity is inhibited in arcuate and paraventricular hypothalamus (PVH) by the anorexigenic hormone leptin, and in multiple hypothalamic regions by insulin, high glucose and refeeding. A melanocortin receptor agonist, a potent anorexigen, decreases AMPK activity in PVH, whereas agouti-related protein, an orexigen, increases AMPK activity. Melanocortin receptor signalling is required for leptin and refeeding effects on AMPK in PVH. Dominant negative AMPK expression in the hypothalamus is sufficient to reduce food intake and body weight, whereas constitutively active AMPK increases both. Alterations of hypothalamic AMPK activity augment changes in arcuate neuropeptide expression induced by fasting and feeding. Furthermore, inhibition of hypothalamic AMPK is necessary for leptin's effects on food intake and body weight, as constitutively active AMPK blocks these effects. Thus, hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance.

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Numerous cardiac output (CO) monitors have been produced that provide continuous rather than intermittent readings. Bland and Altman has become the standard method for validating their performance against older standards. However, the Bland and Altman method only assesses precision and does not assess how well a device detects serial changes in CO (trending ability). Currently, there is no consensus on how trending ability, or trend analysis, should be performed. Therefore, we performed a literature review to identify articles published between 1997 and 2009 that compared methods of continuous CO measurement. Identified articles were grouped according to measurement technique and statistical methodology. Articles that analyzed trending ability were reviewed with the aim of finding an acceptable statistical method. Two hundred two articles were identified. The most popular methods were pulse contour (69 articles), Doppler (54), bioimpedance (38), and transpulmonary or continuous thermodilution (27). Forty-one articles addressed trending, and of these only 23 provided an in-depth analysis. Several common statistical themes were identified: time plots, regression analysis, Bland and Altman using change in CO (ΔCO), and the 4-quadrant plot, which used direction of change of ΔCO to determine the concordance. This plot was further refined by exclusion of data when values were small. Receiver operating characteristic curves were used to define the exclusion zone. In animal studies, a reliable reference standard such as an aortic flowprobe was frequently used, and regression or time plots could be used to show trending. Clinical studies were more problematic because data collection points were fewer (8-10 per subject). The consensus was to use the 4-quadrant plot with exclusion zones and apply concordance analysis. A concordance rate of >92% when using a 15% zone indicated good trending. A new method of presenting trend data (ΔCO) on a polar plot is proposed. Agreement was shown by the angle with the horizontal axis and ΔCO by the distance from the center. Trending can be assessed by the vertical limits of the data, similar to the Bland and Altman method.