All mammals are provided with two distinct adipose cells, white and brown adipocytes. White adipocytes store lipids to provide fuel to the organism, allowing intervals between meals. Brown adipocytes use lipids to produce heat. Previous descriptions have implied their localization in distinct sites of the body; however, it has been demonstrated that they are present together in many depots, which has led to the new concept of the adipose organ. In order to explain their coexistence the hypothesis of reversible physiological transdifferentiation has been developed, i.e. they are contained together because they are able to convert, one into the other. In effect, if needed the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ is associated with resistance to obesity and its related disorders. A new example of reversible physiological transdifferentiation of adipocytes is offered by the mammary gland during pregnancy, lactation and post-lactation stages. The gravidic hormonal stimulus seems to trigger a transdifferentiation of adipocytes into milk-producing and secreting epithelial glands. In the post-lactation period some of the epithelial cells of the mammary gland seem to transdifferentiate into adipocytes. Recent unpublished results suggest that explanted adipose tissue, as well as explanted isolated mature adipocytes, is able to transdifferentiate into glands with epithelial markers of milk-secreting mammary glands. These findings, if confirmed, seem to suggest new windows into the cell biology frontiers of adipocytes.

Human obesity and its complications are an increasing burden in developed and underdeveloped countries. Adipose tissue mass and the mechanisms that control it are central to elucidating the aetiology of obesity and insulin resistance. Over the past 15 years tremendous progress has been made in several avenues relating to adipose tissue. Knowledge of the lipolytic machinery has grown with the identification of new lipases, cofactors and interactions between proteins and lipids that are central to the regulation of basal and stimulated lipolysis. The dated idea of an inert lipid droplet has been appropriately revamped to that of a dynamic and highly-structured organelle that in itself offers regulatory control over lipolysis. The present review provides an overview of the numerous partners and pathways involved in adipose tissue lipolysis and their interaction under various metabolic states. Integration of these findings into whole adipose tissue metabolism and its systemic effects is also presented in the context of inflammation and insulin resistance.

Adipose tissue has a key role in the development of metabolic syndrome (MS), which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of MS in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose tissue and secretion of pro-inflammatory adipokines. Development of MS could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of MS. The n-3 long-chain (LC) PUFA, EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus, n-3 LC PUFA represent healthy constituents of diets for patients with MS. In rodents n-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects of n-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 LC PUFA.

Expansion of adipose tissue mass, the distinctive feature of obesity, is associated with low-grade inflammation. White adipose tissue secretes a diverse range of adipokines, a number of which are inflammatory mediators (such as TNFα, IL-1β, IL-6, monocyte chemoattractant protein 1). The production of inflammatory adipokines is increased with obesity and these adipokines have been implicated in the development of insulin resistance and the metabolic syndrome. However, the basis for the link between increased adiposity and inflammation is unclear. It has been proposed previously that hypoxia may occur in areas within adipose tissue in obesity as a result of adipocyte hypertrophy compromising effective O2 supply from the vasculature, thereby instigating an inflammatory response through recruitment of the transcription factor, hypoxic inducible factor-1. Studies in animal models (mutant mice, diet-induced obesity) and cell-culture systems (mouse and human adipocytes) have provided strong support for a role for hypoxia in modulating the production of several inflammation-related adipokines, including increased IL-6, leptin and macrophage migratory inhibition factor production together with reduced adiponectin synthesis. Increased glucose transport into adipocytes is also observed with low O2 tension, largely as a result of the up-regulation of GLUT-1 expression, indicating changes in cellular glucose metabolism. Hypoxia also induces inflammatory responses in macrophages and inhibits the differentiation of preadipocytes (while inducing the expression of leptin). Collectively, there is strong evidence to suggest that cellular hypoxia may be a key factor in adipocyte physiology and the underlying cause of adipose tissue dysfunction contributing to the adverse metabolic milieu associated with obesity.

A strong causal link between increased adipose tissue mass and insulin resistance in tissues such as liver and skeletal muscle exists in obesity-related disorders such as type 2 diabetes. Increased adipose tissue mass in obese patients and patients with diabetes is associated with altered secretion of adipokines, which also includes chemotactic proteins. Adipose tissue releases a wide range of chemotactic proteins including many chemokines and chemerin, which are interesting targets for adipose tissue biology and for biomedical research in obesity and obesity-related diseases. This class of adipokines may be directly linked to a chronic state of low-grade inflammation and macrophage infiltration in adipose tissue, a concept intensively studied in adipose tissue biology in recent years. The inflammatory state of adipose tissue in obese patients may be the most important factor linking increased adipose tissue mass to insulin resistance. Furthermore, chemoattractant adipokines may play an important role in this situation, as many of these proteins possess biological activity beyond the recruitment of immune cells including effects on adipogenesis and glucose homeostasis in insulin-sensitive tissues. The present review provides a summary of experimental evidence of the role of adipose tissue-derived chemotactic cytokines and their function in insulin resistance in vivo and in vitro.

Profound loss of adipose and other tissues is a hallmark of cancer cachexia, a debilitating condition associated with increased morbidity and mortality. Fat loss cannot be attributable to reduced appetite alone as it precedes the onset of anorexia and is much more severe in experimental models of cachexia than in food restriction. Morphological examination has shown marked remodelling of adipose tissue in cancer cachexia. It is characterised by the tissue containing shrunken adipocytes with a major reduction in cell size and increased fibrosis in the tissue matrix. The ultrastructure of ‘slimmed’ adipocytes has revealed severe delipidation and modifications in cell membrane conformation. Although the molecular mechanisms remain to be established, evidence suggests that altered adipocyte metabolism may lead to adipose atrophy in cancer cachexia. Increased lipolysis appears to be a key factor underlying fat loss, while inhibition of adipocyte development and lipid deposition may also contribute. Both tumour and host-derived factors are implicated in adipose atrophy. Zinc-α2-glycoprotein (ZAG), which is overexpressed by certain malignant tumours, has been identified as a novel adipokine. ZAG transcripts and protein expression in adipose tissue are up regulated in cancer cachexia but reduced with adipose tissue expansion in obesity. Studies in vitro demonstrate that recombinant ZAG stimulates lipolysis. ZAG may therefore act locally, as well as systemically, to promote lipid mobilisation in cancer cachexia. Further elucidation of ZAG function in adipose tissue may lead to novel targets for preventing adipose atrophy in malignancy.

The emerging role of adipose tissue as a dynamic endocrine organ with an extent of anatomical and physiological plasticity has generated numerous studies linking early-life events with long-term alterations in adipose tissue structure and function. Coupled with increasing rates of human obesity, which cannot be explained without some genetic component, the role of early programming of adipose tissue may provide an insight into potential mechanisms. The developmental origins of health and disease hypothesis investigates the potential association between a compromised fetal and postnatal environment and later disease, such as obesity and type 2 diabetes, in the offspring. A number of animal models have been developed to examine potential mechanisms that drive these physiological changes, including rodent and large-mammal models that provide mechanistic insights into the epidemiological findings. In utero challenges such as under- or over-provision of nutrients, placental insufficiency and glucocorticoid infusion, as well as postnatal nutritional challenges, can all result in the long-term programming of adipose tissue abundance and function. A range of hormones, enzymes, transcription factors and other metabolic signalling molecules have been implicated in adverse adipose tissue development, including leptin, glucocorticoids, members of the PPAR family, fatty acid-binding proteins and adipokines. The long-term structural and physiological consequences associated with these molecular and cellular changes are less well described. The experimental models, potential mechanisms and regulators of the early programming of adipose tissue in large mammalian species will be summarised in the present review.

According to the adipostat hypothesis for body-weight control, alterations in body weight should always be compensated by adequate alterations in food intake and thermogenesis. Thus, increased thermogenesis should not be able to counteract obesity because food intake would be increased. However evidence is presented here that thermogenesis in different forms (through artificial uncouplers, exercise, cold exposure) may counteract obesity and is not always fully compensated by increased food intake. Correspondingly, a decreased capacity for metaboloregulatory thermogenesis (i.e. non-functional brown adipose tissue) may in itself lead to obesity. This is evident in mice and may be valid for human subjects, as a substantial proportion of adults possess brown adipose tissue, and those with less or without brown adipose tissue would seem to be more prone to obesity. Thus, increased thermogenesis may counteract obesity, without dietary intervention.

Nutrition can affect the brain throughout the life cycle, with profound implications for mental health and degenerative disease. Many aspects of nutrition, from entire diets to specific nutrients, affect brain structure and function. The present short review focuses on recent insights into the role of nutrition in cognition and mental health and is divided into four main sections. First, the importance of nutritional balance and nutrient interactions to brain health are considered by reference to the Mediterranean diet, energy balance, fatty acids and trace elements. Many factors modulate the effects of nutrition on brain health and inconsistencies between studies can be explained in part by differences in early environment and genetic variability. Thus, these two factors are considered in the second and third parts of the present review. Finally, recent findings on mechanisms underlying the actions of nutrition on the brain are considered. These mechanisms involve changes in neurotrophic factors, neural pathways and brain plasticity. Advances in understanding the critical role of nutrition in brain health will help to fulfil the potential of nutrition to optimise brain function, prevent dysfunction and treat disease.

Changes in maternal diet at different stages of reproduction can have pronounced influences on the health and well-being of the resulting offspring, especially following exposure to an obesogenic environment. The mechanisms mediating adaptations in development of the embryo, placenta, fetus and newborn include changes in the maternal metabolic environment. These changes include reductions in a range of maternal counter-regulatory hormones such as cortisol, leptin and insulin. In the sheep, for example, targeted maternal nutrient restriction coincident with the period of maximal placental growth has pronounced effects on the development of the kidney and adipose tissue. As a consequence, the response of these tissues varies greatly following adolescent-onset obesity and ultimately results in these offspring exhibiting all the symptoms of the metabolic syndrome earlier in young adult life. Leptin administration to the offspring after birth can have some long-term differential effects, although much higher amounts are required to cause a response in small compared with large animal models. At the same time, the responsiveness of the offspring is gender dependent, which may relate to the differences in leptin sensitivity around the time of birth. Increasing maternal food intake during pregnancy, either globally or of individual nutrients, has little positive impact on birth weight but does impact on liver development. The challenge now is to establish which components of the maternal diet can be sustainably modified in order to optimise the maternal endocrine environment through pregnancy, thus ensuring feto–placental growth is appropriate in relation to an individual's gender and body composition.

Nutrition in early life, a critical period for human development, can have long-term effects on health in adulthood. Supporting evidence comes from epidemiological studies, animal models and experimental interventions in human subjects. The mechanism is proposed to operate through nutritional influences on growth. Substantial evidence now supports the hypothesis that ‘accelerated’ or too fast infant growth increases the propensity to the major components of the metabolic syndrome (glucose intolerance, obesity, raised blood pressure and dyslipidaemia), the clustering of risk factors that predispose to cardiovascular morbidity and mortality. The association between infant growth and these risk factors is strong, consistent, shows a dose–response effect and is biologically plausible. Moreover, experimental data from prospective randomised controlled trials strongly support a causal link between infant growth and later risk factors for atherosclerosis. Evidence that infant growth affects the development of atherosclerosis therefore suggests that the primary prevention of CVD should begin from as early as the first few months of life. The present review considers this evidence, the underlying mechanisms involved and its implications for public health.

Cystic fibrosis (CF) is a complex multisystem disorder affecting mainly the gastrointestinal tract and respiratory system. Intestinal malabsorption occurs in approximately 90% of patients. In the past, malnutrition was an inevitable consequence of disease progression, leading to poor growth, impaired respiratory muscle function, decreased exercise tolerance and immunological impairment. A positive association between body weight and height and survival has been widely reported. The energy requirements of patients with CF vary widely and generally increase with age and disease severity. For many young adults requirements will be 120–150% of the age-related estimated average requirement. To meet these energy needs patients are encouraged to eat a high-fat high-energy diet with appropriate pancreatic enzyme supplements. Many patients are unable to achieve an adequate intake as a result of a variety of factors including chronic poor appetite, infection-related anorexia, gastro-oesophageal reflux and abdominal pain. Oral energy supplements and enteral tube feeding are widely used. Nutritional support has been shown to improve nutritional status and stabilise or slow the rate of decline in lung function. With such emphasis on nutritional intake and nutritional status throughout life, poor adherence to therapies and issues relating to body image are emerging. The median survival of patients with CF is increasing. CF is now considered a life-limiting disease of adulthood rather than a terminal childhood illness. With increased longevity new challenges are emerging that include the transition of young adults with CF to adult services, CF-related diabetes, disordered eating, osteoporosis, liver disease and transplantation.

Pharmacological, surgical and technological advances have resulted in children now surviving through adolescence into adulthood with conditions that were previously unseen by adult services. Arranging transition for young people on home parenteral nutrition (HPN) to the adult sector is one of greatest challenges for health services that care for young people. Transition is not only a key quality issue for health services, but is a multidimensional process covering psychosocial, educational and vocational aspects. Poorly-planned transition may result in difficulties when young people access adult specialist services. As a consequence, there may be increased risk of non-adherence or lack of follow-up, which carries dangers of morbidity and mortality as well as poor social and educational outcomes. Transition does not end at the exit from the paediatric clinic, but continues into the adult sector, which needs to provide developmentally-appropriate clinical care. Recent Department of Health initiatives are aimed at ensuring that young people do not miss out on healthcare during the transfer between paediatric and adult services. Transfer can be a major, often daunting, event for young people. Parents may also fear transfer and need to learn to ‘let go’ of some control, which may be particularly difficult with a young person on HPN.