Review Articles in 2015

Patients with congenital generalized lipodystrophy (CGL) have a near total absence of body fat owing to mutations in genes involved in lipid storage. This Review describes the genetic pathophysiology of the four main forms of CGL and makes recommendations for their appropriate diagnosis and management. Specific therapies for CGL are currently limited, but the authors highlight novel drugs currently in development to treat this condition.

Nicotinamide phosphoribosyltransferase (NAMPT) regulates the biosynthesis of nicotinamide adenine dinucleotide (NAD), levels of which are decreased in various metabolic disorders and during ageing. Here, Antje Garten and colleagues discuss the physiological functions of NAMPT and its relevance in various human diseases and conditions such as obesity, nonalcoholic fatty liver disease, type 2 diabetes mellitus, cancer and ageing.

Increased intake and reduced expenditure of energy results in obesity and must be appropriately controlled to prevent this disease state. In this Review, Denis Richard discusses how the central nervous system and peripheral signals from the gut interact to control energy homeostasis and thermogenesis of brown adipose tissue in states of obesity.

Bariatric and metabolic surgeries are increasingly being used to treat patients with obesity, which is a major public health challenge. In this Review, Gema Frühbeck discusses the current body of evidence related to the outcomes of bariatric and metabolic surgery. Frühbeck suggests that a paradigm shift in eligibility and success criteria is required. She proposes that patient selection and follow-up should no longer focus solely on weight and BMI.

In this Review, Joshua Farr and Sundeep Khosla discuss changes in bone architecture during growth, placing an emphasis on skeletal changes at the distal radius, a clinically relevant site of forearm fractures. The implications of these changes for fracture risk in adolescence and later in life, and the architectural changes in bone with ageing that might contribute to increased fracture risk are also discussed.

All women, regardless of ethnicity, geographic location or culture will transition through perimenopause. Many of the neurological symptoms that emerge during this transition are the result of estrogen depletion in the brain. In this Review, the authors discuss the neurological symptoms associated with perimenopause in the context of estrogen-mediated processes in the brain.

Whole-exome sequencing (WES) can effectively sequence >90% of the coding DNA in an individual, and reveal potential disease-causing genetic variants. In this Review, de Bruin and Dauber discuss the use of WES in the field of endocrinology, how this technique can reveal new insights into both rare and common disorders, and its future use in a clinical environment.

Osteoporosis is a process operative in almost all individuals past middle age and results in fractures in a large proportion of men and women. In this Review, Ian Reid reflects on the nature of the osteoporotic process and its implications for treatment indications, and considers the pros and cons of available interventions to reduce fracture risk.

Although reported to improvein vitrofertilization outcomes, androgen supplementation of women with low functional ovarian reserve (LFOR) has remained controversial. In this Review, Aya Shohat-Tal and colleagues discuss genetic variants and polymorphisms associated with inefficient metabolism of dehydroepiandrosterone (DHEA) to testosterone and how, following DHEA supplementation, the hormonal profiles of hypoandrogenic women reflect their ability to metabolize DHEA to testosterone.

Thyroid hormones regulate many metabolic and developmental processes, including key functions in the brain, and mutations in a transporter specific for thyroid hormone lead to severe neurological impairment. In this Review, Bernal and colleagues discuss the physiological importance and clinical implications of thyroid hormone transport, with a particular focus on brain development.

Disorders of sex development (DSDs) are caused by a broad range of genetic changes, but can be difficult to diagnose. In the past few years, advances have been made in molecular diagnostics that could affect the diagnosis of DSDs. This Review analyses the contribution of molecular biology techniques to the diagnosis and management of DSDs, as well as discussing advances in these techniques.

Epicardial adipose tissue is a multifaceted fat depot with unique metabolic, thermogenic and mechanical properties. Here, Gianluca Iacobellis reviews the pathophysiology of this distinctive fat depot with regard to its function in health and disease, as well as addressing a role for epicardial fat as a biomarker for cardiometabolic disease and measuring the efficacy of treatments that target metabolic diseases.

Islet α cells produce glucagon, which is an important regulator of blood glucose levels under fasting conditions. Dysregulated glucagon secretion is a hallmark of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Here, Campbell and Drucker review current understanding of α cells, as well as glucagon secretion and action in normal physiology and in diabetes mellitus. The consequences of selectively enhancing or attenuating glucagon action for the treatment of T1DM and T2DM are also addressed.

Obesity is associated with inflammatory responses in the brain, particularly the hypothalamus, which could open up new therapeutic targets. This Review will discuss the innate immune response in the hypothalamic neuron–glial circuit to obesity and associated metabolic disorders and propose corresponding strategies for treating obesity.

The role of prolactin in processes such as lactation and reproduction is well established. However, in the past few years, numerous novel functions for this hormone have been elucidated. In this Review, Bernard and colleagues discuss these newly described functions for prolactin, in particular, the mechanisms underlying infertility associated with hyperprolactinaemia, and the discovery of a mutation in the gene that encodes the prolactin receptor.

The extracellular calcium-sensing receptor (CaSR) is a G protein-coupled receptor that has a key role in Ca²⁺homeostasis via its role in the parathyroid glands and kidneys. New evidence has shown that CaSR also regulates skeletal homeostasis. In this Review, David Goltzman and Geoffrey Hendy discuss the role of CaSR in chondrocytes and development of the cartilagenous growth plate, in osteoblasts and osteoclasts, and effects of CaSR on skeletal development and bone turnover.

MicroRNAs (miRNAs) regulate the differentiation of adipoctyes, as well as endocrine and inflammatory processes in adipose tissues. In this Review, Arner and Kulyté addressed the characterization and functions of miRNA regulatory networks in human adipose tissue, in particular the networks that contribute to chronic low-level inflammation. The potential for targeting these networks, as well as individual miRNAs, in obesity and other metabolic disorders is also discussed.

Chylomicronaemia is a challenging metabolic disorder that presents in two distinct primary forms: rare monogenic early-onset chylomicronaemia and polygenic late-onset chylomicronaemia. In this Review, Amanda Brahm and Robert Hegele discuss the genetic basis of the disorder and present a framework for the diagnosis and treatment of patients with severe hypertriglyceridaemia that results from chylomicronaemia.

In contemporary society, the ready availability of calorie-dense, highly palatable foods has contributed to the global obesity epidemic. Individuals with obesity often consume an excess of food, despite knowledge of the associated adverse consequences. In this Review, Santa-Cruz Calvo and Egan explore the physiology of taste perception with regard to taste receptors, neuronal signalling and hormonal control of food intake.

The replacement or regeneration of pancreatic β cells has the potential to reverse the progression of diabetes mellitus. This Review discusses the physiology of normal β-cell replication, the signalling pathways and epigenetic mechanisms that regulate entry to the cell cycle in β cells, and approaches for discovering novel molecules that drive β-cell replication. The potential and challenges of implementing strategies that replace or regenerate β-cells in humans is also discussed.