Celebrating and reflecting on 15 years of Nature Reviews Endocrinology, and looking towards to next 15 years.
To celebrate the 15th anniversary of Nature Reviews Endocrinology, we have collated a collection of some of our most popular articles, as well as a series of Comments discussing six key articles from the past 15 years.
Commentaries and opinions
Islet inflammation (insulitis) in type 1 diabetes mellitus is triggered by a deleterious dialogue between β-cells and the immune system, inducing β-cell dysfunction and death. This concept, outlined in our 2009 Review, has been confirmed and extended. Here, we provide a brief update of the field and outline key pending questions.
In 2012, we were invited by Nature Reviews Endocrinology to write a Review titled ‘Muscles, exercise and obesity: skeletal muscle as a secretory organ’. At the time, following our findings in the 2000s, we knew the concept of skeletal muscle as an endocrine organ was important. Eight years on, the magnitude of the importance of this concept surprises us.
In 2019, we published a Review on the relevance of gut microbial metabolites in obesity, non-alcoholic fatty liver disease and type 2 diabetes mellitus. Here, we highlight the importance of the balance between colonic proteolytic and saccharolytic metabolite production for metabolic health and the need to focus on more subgroup-based or personalized nutritional approaches.
In the past decade, the prevalence of obesity and related comorbidities has continued to increase across the globe, prompting many countries to adopt policies to improve diet quality. Here, we discuss key nutrition policies that have been implemented in the past few years and consider future priorities for global obesity prevention.
This Comment article provides a behind-the-scenes perspective and update of our 2016 Review, which discussed possible factors contributing to thyroid cancer incidence trends worldwide. We also highlight promising research directions that are improving the understanding of thyroid cancer aetiology.
The first International Symposium on Phaeochromocytoma in 2005 was followed by considerable progress in the field, largely owing to the many collaborations and networks stimulated by that and subsequent meetings. The rich hereditary background of phaeochromocytomas has since provided for strong interdisciplinary links of genetics with personalized diagnostics, imaging and therapeutic interventions.
The prevalence of obesity has increased worldwide in the past ~50 years, reaching pandemic levels. Remarkable regional differences exist in obesity prevalence and trends, which might help to identify societal causes of obesity and provide guidance for the most promising intervention strategies.
In this Review, the authors explore the role of gut microbial metabolites derived from carbohydrate fermentation and protein fermentation in body weight control, nonalcoholic fatty liver disease, insulin resistance and type 2 diabetes mellitus.
Animal models are necessary for the discovery, validation and optimization of novel therapeutics. Here, Matthias Tschöp and colleagues consolidate the key information on the currently available animal models of obesity and diabetes mellitus and highlight the advantages, limitations and important caveats of each of these models.
The global epidemic of type 2 diabetes mellitus (T2DM) and its complications is a major threat to public health. This Review provides an updated view of the global epidemiology of T2DM and the dietary, lifestyle and other risk factors for T2DM and its complications.
Targeting the immune system in tumour cells has become a central therapy for cancer treatment, but such drugs can lead to adverse effects. In this Review, the authors describe the immune-related endocrinopathies, such as hypophysitis, thyroid dysfunction and the development of diabetes mellitus that can result from cancer immunotherapy.
Adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Here, Reilly and Saltiel review the cellular and molecular mechanisms of obesity-induced inflammation in adipose tissue and discuss potential therapeutic approaches.
The incidence of thyroid cancer has increased substantially in many countries over the past few decades. In this Review, Kitahara and Sosa describe the changing incidence of the disease and suggest possible explanations for the trends, emphasizing implications for patients and ongoing strategies to combat this growing public health issue.
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.
European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment
Congenital hypogonadotropic hypogonadism (CHH)—a rare disorder caused by deficient production, secretion or action of gonadotropin-releasing hormone—results in an absence of puberty and infertility. Here, Ulrich Boehm and colleagues summarize approaches for the diagnosis and treatment of CHH in light of recent discoveries. This Consensus Statement differs from existing guidelines for the treatment of hypogonadism as it focuses exclusively on CHH.
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.
Clinical manifestations of hypovitaminosis D, a highly prevalent disorder worldwide, include musculoskeletal disorders as well as nonclassical manifestations, such as increased risk of respiratory infections, diabetes mellitus and possibly cardiovascular diseases. This Review discusses the prevalence of hypovitaminosis D across the lifecycle, and risk factors and health outcomes associated with it in developing countries.
An increased incidence of malformations of the genital tract, and neoplasms of the testis, uterus, and breast has been observed during the past half century following the introduction of endocrine disrupting chemicals into the environment. This Review discusses the theoretical underpinnings and corresponding evidence connecting development and carcinogenesis. The data gathered thus far linking exposure to these chemicals to cancer warrant action to protect public health.
Knowledge of genetic alterations occurring in thyroid cancer has rapidly expanded in the past decade. This Review discusses genetic alterations in follicular cell-derived thyroid cancers and outlines new insights into thyroid cancer etiology; in addition, the article describes how mutational markers can be used to improve cancer diagnosis and prognostication.
This Review discusses the genetic, prenatal and environmental antecedents of polycystic ovary syndrome. The reproductive, metabolic, cardiovascular, psychiatric and neoplastic complications of this common condition are presented, followed by a comprehensive discussion of diagnostic and therapeutic measures.
There is an epidemic of type 2 diabetes mellitus in nearly every nation in the world. This Review gives an overview of the current trends of the diabetes epidemic in a world scenario and discusses the associated major risk factors, particularly genetic and epigenetic factors. The potential impact of the use of HbA1cas an alternative diagnostic tool on global diabetes surveillance is also discussed.
Skeletal muscle has the capacity to produce, express and release several hundred secreted peptides, so-called myokines. This finding provides a conceptual basis and a new paradigm for understanding the role of skeletal muscle in organ crosstalk, including muscle–liver and muscle–adipose tissue crosstalk. This Review highlights the clinical role of myokines in mediating the multiple health benefits of exercise.
Measuring circulating levels of microRNAs is a promising strategy for identifying people at risk of developing diabetes mellitus; however, several obstacles still need to be overcome before this strategy can be used in clinical practice. This Review summarizes the weaknesses of current biomarkers and discusses the potential use of microRNAs as novel biomarkers.
The worldwide increase in obesity has been driven by global trade liberalization, economic growth and rapid urbanization. Owing to the scope and complexity of the obesity epidemic, prevention strategies and policies across multiple levels are needed in order to have a measurable effect. Although many putative causes of the obesity epidemic exist, in this Review the effect of globalization on global trends in obesity prevalence is discussed and population-based interventions from several countries are reviewed. The authors make broad policy recommendations for obesity and chronic disease prevention at the global population level.
This Review discusses the molecular mechanisms through which metformin acts on metabolism, mainly focussing on liver gluconeogenesis, and on tumourigenesis. In addition, the authors review the potential implications of new discoveries about the molecular targets of metformin for the development of antidiabetic and anticancer therapies.
Endometriosis is a chronic inflammatory disease affecting around 5% of reproductive age women, often causing pelvic pain and infertility. This Review addresses current knowledge on the pathogenesis of the condition, medical, surgical and potential new treatments, the role of assisted reproduction, prevention of recurrences, and the association with ovarian cancer.
Thyroid-cell proliferation depends on TSH; suppression of TSH with levothyroxine decreases progression and recurrence rates for thyroid cancer. Long-term TSH suppression benefits patients at high risk of cancer recurrence but not low-risk patients, so TSH levels should be targeted accordingly.
Proglucagon-derived peptides from the pancreas and gut regulate various aspects of energy homeostasis, with many potential therapeutic applications—glucagon is used to treat hypoglycemia, and researchers are testing glucagon antagonists and glucagon-derived peptide 1 receptor (GLP-1R) agonists to treat type 2 diabetes, and a GLP-2 analogue to treat short-bowel syndrome.
Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging
Testosterone use as anabolic therapy is controversial. Here, meta-analyses show that testosterone increases skeletal muscle mass and strength in androgen-deficient young men, older men and men with chronic illness; these data provide a compelling rationale for the development of selective androgen receptor modulators that mimic testosterone's effects without its side effects.
Excess free fatty acids, an imbalance of adipocytokines and mitochondrial dysfunction all contribute to abnormalities in hepatocellular lipid content in diabetes and can lead to steatosis and insulin resistance. Thus liver fat is a novel target for therapies such as fat-reduced diets and thiazolidendiones.
Pheochromocytomas are rare, often hereditary, catecholamine producing tumors that can be difficult to diagnose and manage. This Review summarizes the recommendations for biochemical and genetic testing, localization and treatment, and is based on discussions at the First International Symposium on Pheochromocytoma, held in October 2005.
Mechanisms of Disease: glucocorticoids, their placental metabolism and fetal 'programming' of adult pathophysiology
This Review describes effects of maternal factors such as diet and glucocorticoid levels on disease development later in the child's life. In particular, the barrier function of placental 11β-hydroxysteroid dehydrogenase type 2 in controlling fetal glucocorticoid exposure, and mechanisms that affect glucocorticoid receptor promoter usage and gene methylation are discussed.
Mechanisms of Disease: advanced glycation end-products and their receptor in inflammation and diabetes complications
Injury to the vasculature is an important adverse outcome in diabetes. In this Review, Yan et al. explore how advanced glycation end-products and their main receptor, RAGE, might have roles in the development of diabetes and some of its complications–nephropathy, atherosclerosis and inflammatory response–through activation of inflammatory signaling cascades.
Between 20% and 40% of patients with diabetes ultimately develop nephropathy. The bank of data on the multiple and complex mechanisms, disease markers and disease progression continues to grow. This article provides an overview of the current status of findings relating to underlying mechanisms and genetic susceptibility.
Innate immunity and inflammatory mediators have been suggested to have a much broader role in type 1 diabetes mellitus than initially assumed. Inflammation might contribute to early induction and amplification of the immune assault against pancreatic β-cells and, at later stages, to the stabilization and maintenance of insulitis. This review summarizes the latest findings that demonstrate the role of inflammation in the different phases of the course of type 1 diabetes mellitus.
Physical or emotional effects that potentially threaten homeostasis activate various compensatory mechanisms coordinated by the stress system. This article provides an overview of the conceptual evolution and current understanding of homeostasis and stress, the main effectors and targets of the stress response and the effects of stress on the organism.