Neuropeptide Y (NPY) stimulates feeding and weight gain, but deletion of the NPY gene does not affect food intake and body weight in mice bred on a mixed genetic background. We reasoned that the orexigenic action of NPY would be evident in C57Bl/6J mice susceptible to obesity. NPY deficiency has no significant effect in mice fed a normal rodent diet. However, energy expenditure is elevated during fasting, and hyperphagia and weight gain are blunted during refeeding. Expression of agouti-related peptide (AGRP) in the hypothalamus is increased in NPY knockout (NPYko) than wild-type mice, but unlike wild type there is no further increase in AGRP when NPYko mice are fasted. Moreover, NPYko mice have higher oxygen consumption and uncoupling protein-1 expression in brown adipose tissue during fasting. The failure of an increase in orexigenic peptides and higher thermogenesis may contribute to attenuation of weight gain when NPYko mice are refed. C57Bl/6J mice lacking NPY are also less susceptible to diet-induced obesity (DIO) as a result of reduced feeding and increased energy expenditure. The resistance to DIO in NPYko mice is associated with a reduction in nocturnal feeding and increased expression of anorexigenic hypothalamic peptides. Insulin, leptin, and triglyceride levels increase with adiposity in both wild-type and NPYko mice. Diabetes 55:3091-3098, 2006 E nergy balance involves a complex interaction between hormones, such as leptin, insulin, and glucocorticoids, and key neurons in the hypothalamus, brainstem, and other areas of the central nervous system (1). Neuropeptide Y (NPY) is expressed in the hypothalamus, stimulates food intake, decreases energy expenditure, and increases body weight when administered in the brain (1). Consistent with its role as an orexigenic peptide, hypothalamic NPY expression is increased during fasting and hypoglycemia and suppressed by feeding, leptin, and insulin (1). Despite the strong pharmacological evidence supporting its role in energy balance, genetic disruption of NPY did not affect feeding or body weight in mice bred on a mixed 129J-C57Bl/6J background (2). Paradoxically, deletion of NPY or the Y1 and Y5 receptors that mediate effects of NPY on energy balance resulted in mild obesity (3-6). Nonetheless, loss of NPY attenuated hyperphagia and obesity in Lep ob/ob mice (7). Others have also shown that NPY deficiency decreases hyperphagia after fasting and hypoglycemia (8 -10). Furthermore, deletion of NPY Y2/Y4 receptors prevents diet-induced obesity (DIO) (11).We reasoned that the controversies surrounding the actions of NPY in these genetic models are partly due to the use of the 129 mouse strain, which is resistant to obesity (12). The seemingly normal phenotype of NPYdeficient mice could also result from compensatory developmental changes. For example, ablation of hypothalamic neurons expressing NPY/AGRP did not alter feeding in neonatal mice, whereas ablation in adults caused starvation (13,14). AGRP is coexpressed with NPY in the arcuate nucleus, and both peptides ...

Neuropeptide Y (NPY), whose role in appetite regulation is well known, is also expressed in pancreatic islets. Although previous studies indicated that application of NPY to pancreatic islets inhibits insulin secretion, its physiological role in the regulation of insulin secretion is not fully understood. We hypothesized that NPY in islets tonically suppresses insulin secretion and the reduction of islet NPY increases insulin secretion. To address the hypothesis, islet function of NPY-deficient mice was analyzed. Although there was little change in glucose homeostasis in vivo, pancreatic islets from NPY-deficient mice had higher basal insulin secretion (1.5 times), glucose-stimulated insulin secretion (1.5 times), and islet mass (1.7 times), compared with wild-type mouse. Next we sought to determine whether the expression of NPY and Y(1) receptor in islets was altered in hyperinsulinemia associated with obesity. Islets from C57BL/6J mice on a high-fat diet had 1.9 times higher basal insulin secretion and 2.4 times higher glucose-stimulated insulin secretion than control mice, indicating islet adaptation to obesity. Expression of NPY and Y(1) receptor mRNA levels was decreased by 70 and 64%, respectively, in high-fat diet islets, compared with controls. NPY and Y(1) receptor in islets were also reduced by 91 and 80%, respectively, in leptin-deficient ob/ob mice that showed marked hyperinsulinemia. Together these results suggest that endogenous NPY tonically inhibits insulin secretion from islets and a reduction of islet NPY may serve as one of the mechanisms to increase insulin secretion when islets compensate for insulin resistance associated with obesity.

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A comprehensive strategy is important for ensuring reproducible and safe acetabular component sizing and positioning. Presented here is our approach for anatomic acetabular component positioning in direct anterior total hip arthroplasty. This strategy has evolved with our understanding of the ramifications of socket sizing and positioning on instability and impingement. Data collected by a single surgeon (J.A.R.) between 2009 and 2011 influenced our current paradigm. We compare the sizing and positioning parameters of the anterior and posterior approach, thus demonstrating how the 2 are different. By highlighting these differences, we hope to provide a clear, defined approach to acetabular placement and sizing for direct anterior-approach total hip arthroplasty.