Articles in 2015

Lysosomal acid lipase deficiency can lead to liver failure and early death. A recently published placebo-controlled trial shows that enzyme-replacement therapy improves plasma levels of lipids and aminotransferases, and reduces liver fat content. However, the effect on clinical end points and an appropriate indication for treatment remain to be established.

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.

The past decade has witnessed incredible advances in the field of reproductive endocrinology. The use of new genetic and genomic tools has had a particular impact, leading to advances in our understanding, diagnosis and treatment of reproductive endocrine disorders, particularly those related to the neuroendocrine control of reproduction and ovarian biology.

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.

Here, five of our Advisory Board Members look back at the past decade of endocrinology research, highlighting key advances and identifying roadblocks. They also discuss where effort and money should be invested now and speculate on where progress might be made in the coming decade.

The past decade has seen exciting progress in the field of thyroid disease, especially in the evaluation of thyroid nodules, the genomic characterization of carcinomas and the treatment of carcinomas after surgery. An improved understanding of hyperthyroidism during pregnancy, as well as the causes of 'low T₃ syndrome' and consumptive hypothyroidism have also been achieved.

The mechanistic link between the FTO locus and risk of obesity has remained elusive. However, a new study presents compelling evidence suggesting that the browning of white adipocytes into beige adipocytes (together with regulation of thermogenesis), might be an important and potentially modifiable pathway for development of obesity therapeutics.

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.