Fibroblast growth factors:new insights, new targets in the management of diabetes

The fibroblast growth factor (FGF) family consists of 22 evolutionarily and structurally related proteins (FGF1 to FGF23; with FGF15 being the rodent ortholog of human FGF19). Based on their mechanism of action, FGFs can be categorized into intracrine, autocrine/paracrine and endocrine subgroups. Both autocrine/paracrine and endocrine FGFs are secreted from their cells of origin and exert their effects on target cells by binding to and activating specific single-pass transmembrane tyrosine kinase receptors (FGFRs). Moreover, FGF binding to FGFRs requires specific cofactors, namely heparin/heparan sulfate proteoglycans or Klothos for autocrine/paracrine and endocrine FGF signaling, respectively. FGFs are vital for embryonic development and mediate a broad spectrum of biological functions, ranging from cellular excitability to angiogenesis and tissue regeneration. Over the past decade certain FGFs (e.g. FGF1, FGF10, FGF15/FGF19 and FGF21) have been further recognized as regulators of energy homeostasis, metabolism and adipogenesis, constituting novel therapeutic targets for obesity and obesity-related cardiometabolic disease. Until recently, translational research has been mainly focused on FGF21, due to the pleiotropic, beneficial metabolic actions and the relatively benign safety profile of its engineered variants. However, increasing evidence regarding the role of additional FGFs in the regulation of metabolic homeostasis and recent developments regarding novel, engineered FGF variants have revitalized the research interest into the therapeutic potential of certain additional FGFs (e.g. FGF1 and FGF15/FGF19). This review presents a brief overview of the FGF family, describing the mode of action of the different FGFs subgroups, and focuses on FGF1 and FGF15/FGF19, which appear to also represent promising new targets for the treatment of obesity and type 2 diabetes.

Symptoms of hyperactivity and inattention can mediate deficits of postural stability in developmental dyslexia

DDevelopmental dyslexia is a reading disorder associated with impaired postural control. However, such deficits are also found in attention deficit hyperactivity disorder (ADHD), which is present in a substantial subset of dyslexia diagnoses. Very few studies of balance in dyslexia have assessed ADHD symptoms, thereby motivating the hypothesis that such measures can account for the group differences observed. In this study, we assessed adults with dyslexia and similarly aged controls on a battery of cognitive, literacy and attention measures, alongside tasks of postural stability. Displacements of centre of mass to perturbations of posture were measured in four experimental conditions using digital optical motion capture. The largest group differences were obtained in conditions where cues to the support surface were reduced. Between-group differences in postural sway and in sway variability were largely accounted for by co-varying hyperactivity and inattention ratings, however. These results therefore suggest that postural instability in dyslexia is more strongly associated with symptoms of ADHD than to those specific to reading impairment.

Attitudes towards emotional expression mediate the relationship between childhood invalidation and adult eating concern

Previous research has suggested that invalidating childhood environments are positively related to the symptoms of eating disorders. However, it is unclear how childhood environments might impact upon the development of eating disorder symptoms. This study examined the relationship between parental invalidation and eating disorder-related attitudes in a nonclinical sample and tested the mediating effect of attitudes towards emotional expression. Two hundred women, with a mean age of 21 years, completed measures of invalidating childhood environments, attitudes towards emotional expression, and eating pathology. Eating concerns were positively associated with recollections of an invalidating parental environment. The belief that the expression of emotions is a sign of weakness fully mediated the relationship between childhood maternal invalidation and adult eating concern. Following replication and extension to a clinical sample, these results suggest that targeting the individual's attitude towards emotional expression might reduce eating attitudes among women who have experienced an invalidating childhood environment. © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.

Do obsessive compulsive symptoms mediate the relationship between maternal eating psychopathology and restrictive feeding practices?

Objective: Symptoms of maternal eating disorders have been linked with the use of maladaptive restrictive child feeding practices. However, how these symptoms impact upon restriction in child feeding is poorly understood. The aims of this research were to assess whether symptoms of obsessive compulsiveness, which are often comorbid with eating disorder symptoms, mediate the relationships between maternal eating disorder symptoms and the use of restrictive feeding practices. Method: A total of 128 mothers of children aged 2-6 years completed measures of their restrictive feeding practices, symptoms of eating disorders, and obsessive compulsiveness. Results: Maternal restriction was positively correlated with symptoms of drive for thinness, bulimia, and checking and cleaning obsessions and compulsions. Cleaning obsessions and compulsions mediated the relationships between maternal drive for thinness and feeding restriction. Conclusion: Cleaning obsessions and compulsions may help to explain the relationships between some symptoms of maternal eating disorders and the use of restrictive feeding practices. © 2008 by Wiley Periodicals, Inc.