Review Articles in 2015

Here, Patrice Cani and colleagues discuss interactions between gut microorganisms, the endocannabinoid system and host metabolism, in the context of both physiology and pathophysiology. The authors highlight the importance of gut barrier function by discussing the role of specific factors involved in intestinal permeability and their role in the gut microbiota–endocannabinoid system axis. The therapeutic potential of targeting the endocannabinoid system to treat cardiometabolic disorders and intestinal inflammation is also discussed.

Diabetic cardiomyopathy is a major cause of morbidity and mortality, and its prevalence is increasing. This Review discusses the latest research in diabetic cardiomyopathy, summarizes current understanding of the molecular mechanisms underpinning this condition and explores potential preventive and therapeutic strategies.

This Review outlines the molecular basis of nongenomic mechanisms of thyroid hormone action. Davis and colleagues also discuss the possible physiological or pathophysiological consequences of these actions, as well as the interactions between nongenomic and genomic effects of thyroid hormone.

Statins are widely used to prevent cardiovascular disease, but have been associated with an increased risk of new-onset diabetes mellitus. This Review discusses the evidence for this association, as well as what is known about the potential mechanisms underpinning this effect. The implications for clinical management of individuals at medium-to-high risk of new-onset diabetes mellitus are also discussed.

Medical therapies for patients with acromegaly are limited by variable efficacy, associated adverse effects and the need for frequent injections. This Review outlines the need for new therapeutic agents for patients with acromegaly, reviews clinical trial data of investigational agents and considers how these therapies might best be integrated into clinical practice in the future.

Here, Denise Lackey and Jerrold Olefsky discuss the innate immune cells involved in secreting inflammatory factors during obesity. The role of innate immune cells in maintaining an anti-inflammatory and insulin-sensitive environment in the lean state is also reviewed. This Review also provides an overview of the mechanisms for regulating proinflammatory immune responses that could lead to future therapeutic opportunities to improve insulin sensitivity.

Changes in protein or histone acetylation are key integrators of physiological processes such as the circadian clock, cell cycle and gene regulation. In this Review, the authors describe the role of reversible acetylation in metabolic control and how these processes contribute to adaptive cellular and organismal homeostasis. The potential for modulating these pathways as a treatment for various metabolic diseases is also discussed.

The skeleton has a central role in the development and regulation of bone metastasis. Here, Larry Suva and colleagues review the skeletal consequences of bone metastasis from an orthopaedic perspective. The authors discuss the effects of existing cancer treatments on bone and the bone marrow microenvironment, as well as the mechanisms mediating these effects and the current utility of modern orthopaedic interventions.

Genetic studies have identified dozens of mutations that are associated with reproductive disorders, including common variants associated with the timing of puberty and/or menopause. This Review discusses the contribution of such genetic findings to our understanding of the molecular regulation of reproductive timing and the biological basis of the epidemiological links between reproductive ageing and disease risk.

In this Review, Martin Heni and colleagues outline the effects of insulin in the brain in humans and the relevance of the effects for physiology. The metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.

In this Review, Jeffrey Baron and colleagues explore the latest discoveries in the molecular and cell biology of childhood growth and in the clinical genetics of childhood growth disorders. These findings challenge the established theory that childhood growth is primarily controlled by growth hormone and insulin-like growth factor 1, leading the authors to suggest a broader framework for understanding linear growth disorders.

T cells are generated in the thymus and exported to peripheral lymphoid organs, a process that is under hormonal control. In this article, the authors discuss the mechanisms of thymus-specific T-cell development and how hormone therapy can counteract the effects of ageing and disease on thymus function.

This Review outlines the physiologic role of the iodothyronine deiodinases, as well as the changes that occur in hypothyroidism, with a particular focus on their role in preserving thyroid hormone levels in the brain. Novel findings that underscore the clinical importance of iodothyronine deiodinases in hypothyroidism are also discussed.

A subclass of endocrine-disrupting chemicals, so-called 'obesogens', have been proposed to predispose certain individuals to weight gain, despite their efforts to limit caloric intake and increase levels of physical activity. In this Review, Jerrold Heindel and colleagues discuss the experimental and epidemiological findings on obesogens, their modes of action, and their role in the obesity epidemic.

Long-chain acylcarnitines (LCACs) are widely used as diagnostic markers in several metabolic disorders; however, research into the potential effects of excessive accumulation of LCACs or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders.

Parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR1) is a family B G-protein-coupled receptor and is involved in the regulation of skeletal development, bone turnover and mineral ion homeostasis. This Review discusses fundamental aspects of ligand-binding and signalling mechanisms at PTHR1, highlighting the relationship between ligand structural modification and variation in PTHR1 signalling responses. The action of these signalling mechanisms in disease states in which PTHR1 function has an important role are also discussed.

For individuals with diabetes mellitus, the lifetime risk of developing a foot ulcer can be as high as 25%, but these complications are preventable. Here, Bowling and colleagues discuss the mechanisms that lead to foot ulcers in patients with diabetes mellitus. The authors emphasise the need for a multidisciplinary management strategy to prevent and treat diabetic foot complications.

Paget's disease is a disorder of bone that manifests in one or several bones and is initiated by osteoclast-induced osteolytic lesions. In addition to a genetic cause, environmental factors, including measles virus, have been proposed to have a role in the pathogenesis of Paget's disease. Here, Frederick R. Singer discusses the present knowledge and controversies surrounding the aetiology of Paget's disease.

Fatty acid-binding proteins (FABPs) improve the solubility of fatty acids. Here, Hotamisligil and Bernlohr describe the structure and function of FABPs in the control of fatty acid metabolism and obesity. The authors focus on FABP4 and FABP5, the most abundant FABPs in adipose tissue, and discuss how targeting these proteins might be exploited to treat metabolic diseases.

Short-chain fatty acids (SCFA) are produced by the gut microbiota from indigestible food stuffs, and might have beneficial effects on metabolism and insulin sensitivity. Here, Canfora and colleagues discuss how SCFA can modulate energy homeostasis and metabolism in adipose tissue, muscle and the liver. The authors also discuss whether SCFA might be used to modulate glucose homeostasis in humans.