Obesity is a major public health problem for which there are few approved medical therapies. Considerable interest exists in the outcome of new drug trials, understanding the mechanisms of obesity and the search for new potential therapeutic targets. Bariatric surgery is a popular obesity therapy and several procedures exist, including gastric bypass, gastric banding and sleeve gastrectomy. Additional approaches, such as adipose tissue transplantation and stem-cell therapy, have also been explored. This article collection from Nature Reviews Endocrinology and Nature Reviews Gastroenterology & Hepatology provides a comprehensive overview of the plethora of current and future approaches to treating obesity.

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REVIEWS

Assessment and management of obesity in childhood and adolescence

Louise A. Baur, Briony Hazelton & Vanessa A. Shrewsbury

doi:10.1038/nrgastro.2011.165

Nature Reviews Gastroenterology & Hepatology 8, 635-645 (2011)

The prevalence of childhood and adolescent obesity is increasing. Although obesity is preventable, effective management in those individuals already affected is crucial as the condition is associated with serious long-term complications. Baur and colleagues address the assessment and management of obesity in children and adolescents, describing key features in the diagnosis, treatment and management of these patients.

Targeting gut microbiota in obesity: effects of prebiotics and probiotics

Nathalie M. Delzenne, Audrey M. Neyrinck, Fredrik Bäckhed & Patrice D. Cani

doi:10.1038/nrendo.2011.126

Nature Reviews Endocrinology 7, 639-646 (2011)

Gut microbes act as an environmental factor that affects an individual's physiology and metabolism, particularly in the context of obesity and its related metabolic disorders. This Review highlights how gut microbes alter the expression of genes involved in the development of obesity and inflammation and focuses on the potential role of specific nutrients that target the gut microbiota.

GLP-1 and energy balance: an integrated model of short-term and long-term control

Jason G. Barrera, Darleen A. Sandoval, David A. D'Alessio & Randy J. Seeley

doi:10.1038/nrendo.2011.77

Nature Reviews Endocrinology 7, 507-516 (2011)

The authors of this Review integrate contributions of both central and peripheral glucagon-like peptide 1 (GLP-1), which is secreted from the intestine in response to nutrient ingestion, in a model of short-term and long-term control of energy balance. This model is discussed with respect to current GLP-1-based therapies and ongoing research that may help maximize the effectiveness of GLP-1-based treatment of obesity.

Surgical approaches to the treatment of obesity

John B. Dixon, Nora E. Straznicky, Elisabeth A. Lambert, Markus P. Schlaich & Gavin W. Lambert

doi:10.1038/nrgastro.2011.112

Nature Reviews Gastroenterology & Hepatology 8, 429-437 (2011)

Bariatric surgery is emerging as an important and broadly available treatment for people with severe and complex obesity that has not responded adequately to other therapy. Gastroenterologists need to be aware of the risks and benefits of current and emerging procedures as they are likely to be increasingly involved in the integrated care of patients. This Review summarizes the evidence for the safety, efficacy and cost-effectiveness of bariatric surgery, as well as discussing mechanisms of action and future directions for surgery.

RNAi-based therapeutic strategies for metabolic disease

Michael P. Czech, Myriam Aouadi & Gregory J. Tesz

doi:10.1038/nrendo.2011.57

Nature Reviews Endocrinology 7, 473-484 (2011)

RNA interference (RNAi) is a robust gene silencing mechanism that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs. This Review describes the current status of research and clinical trials on RNAi-based therapeutics and addresses novel potential targets for the treatment of metabolic disease.

Prospective influences of circadian clocks in adipose tissue and metabolism

Jeffrey M. Gimble, Gregory M. Sutton, Bruce A. Bunnell, Andrey A. Ptitsyn & Z. Elizabeth Floyd

doi:10.1038/nrendo.2010.214

Nature Reviews Endocrinology 7, 98-107 (2011)

Circadian rhythms make a critical contribution to endocrine functions that involve adipose tissue at the systemic, organ and stem cell levels. This Review examines the data that link circadian biology to adipose tissue and its related metabolic organs, such as the liver and pancreas. These findings might affect clinical practice in the coming years.

The metabolic actions of glucagon revisited

Kirk M. Habegger, Kristy M. Heppner, Nori Geary, Timothy J. Bartness, Richard DiMarchi & Matthias H. Tschöp

doi:10.1038/nrendo.2010.187

Nature Reviews Endocrinology 6, 689-697 (2010)

The diabetogenic effect of glucagon has long overshadowed the potential of this pancreatic hormone as an endogenous satiety and anti-obesity factor. This Review discusses the role of glucagon as a beneficial endocrine factor in lipid and energy metabolism and its potential as a therapeutic agent on the basis of studies that combine the agonism of glucagon receptor and glucagon-like peptide 1 receptor.

Addressing childhood obesity through increased physical activity

Andrew P. Hills, Anthony D. Okely & Louise A. Baur

doi:10.1038/nrendo.2010.133

Nature Reviews Endocrinology 6, 543-549 (2010)

Obesity is affecting an increasing proportion of children globally. A multifactorial approach to encouraging young people to be physically active is urgently needed to counteract the obesity epidemic. This Review describes the context of the relationship between obesity and physical inactivity in children, and provides suggestions for a way forward.

Morbid obesity in pediatric diabetes mellitus: surgical options and outcomes

Mary L. Brandt, Carroll M. Harmon, Michael A. Helmrath, Thomas H. Inge, Siripoom V. McKay & Marc P. Michalsky

doi:10.1038/nrendo.2010.167

Nature Reviews Endocrinology 6, 637-645 (2010)

With the growing epidemic of obesity, the number of bariatric surgeries in adolescent patients has continuously increased over the past years. This Review addresses the indications for and against bariatric surgery in adolescents, as well as currently available evidence on clinical outcomes, and summarizes measures to provide adequate postoperative care in this patient population.

Bowels control brain: gut hormones and obesity

Benjamin C. T. Field, Owais B. Chaudhri & Stephen R. Bloom

doi:10.1038/nrendo.2010.93

Nature Reviews Endocrinology 6, 444-453 (2010)

The gastrointestinal tract is an important source of endocrine signals. Gut hormones such as glucagon-like peptide 1, peptide YY, and islet amyloid polypeptide act in an integrated fashion to modulate appetite and energy expenditure. This Review addresses the physiological roles of gut hormones and discusses their potential as targets for the development of novel treatments for obesity, on the basis of pharmacological mimicry of the hormonal milieu after bariatric surgery.

Brown adipose tissue—a new role in humans?

Martin E. Lidell & Sven Enerbäck

doi:10.1038/nrendo.2010.64

Nature Reviews Endocrinology 6, 319-325 (2010)

Several independent studies have shown the presence of functional brown adipose tissue in adult humans. Its innate ability to expend energy via heat production is a feature that could be used to develop new regimens to treat obesity and type 2 diabetes mellitus. This Review outlines the current knowledge on the transcriptional regulation and development of brown adipose tissue and addresses possible targets that may be useful for the expansion and/or activation of brown adipose tissue by pharmacological means.

Managing medical and surgical disorders after divided Roux-en-Y gastric bypass surgery

Bikram Bal, Timothy R. Koch, Frederick C. Finelli & Michael G. Sarr

doi:10.1038/nrgastro.2010.60

Nature Reviews Gastroenterology & Hepatology 7, 320-334 (2010)

This Review provides an overview of the symptoms, complications, nutritional deficiencies and medical disorders associated with Roux-en-Y gastric bypass—the most frequently performed bariatric procedure in the USA and Canada. Although some symptoms are expected and predictable, some complications may require active medical or surgical intervention. Physicians should be able to predict and manage most postoperative medical and nutritional disorders and should be prepared to assess patients for potential referral for surgical intervention or revision.

Pharmacological management of appetite expression in obesity

Jason C. G. Halford, Emma J. Boyland, John E. Blundell, Tim C. Kirkham & Joanne A. Harrold

doi:10.1038/nrendo.2010.19

Nature Reviews Endocrinology 6, 255-269 (2010)

Antiobesity drugs are chosen for their ability to suppress food intake or body weight, with little regard for the psychological factors that influence consumption and weight gain. This Review argues that selective pharmacological targeting of specific emotional and motivational processes that govern appetite and eating may improve outcomes for weight reduction and improved self-control over consumption.

Transplantation of adipose tissue and stem cells: role in metabolism and disease

Thien T. Tran & C. Ronald Kahn

doi:10.1038/nrendo.2010.20

Nature Reviews Endocrinology 6, 195-213 (2010)

Adipose tissue transplantation is increasingly being explored as a treatment strategy for metabolic disease—to promote the beneficial metabolic effects of subcutaneous white adipose tissue and brown adipose tissue, as well as those of adipose-derived stem cells. This Review summarizes the current available data on the biology of different adipose tissue depots and conceptualizes the future of adipose tissue transplantation and ongoing research.

Inflammatory lipid mediators in adipocyte function and obesity

Abishek Iyer, David P. Fairlie, Johannes B. Prins, Bruce D. Hammock & Lindsay Brown

doi:10.1038/nrendo.2009.264

Nature Reviews Endocrinology 6, 71-82 (2010)

Adipocytes store energy and regulate themselves depending on the environment. Clinical studies suggest that excess macronutrient intake may induce cellular lipid loading and promote signs of inflammatory stress, which ultimately leads to metabolic dysfunction. This Review discusses how lipid mediators may act on important immune receptors to induce low-grade tissue inflammation, which leads to adipocyte and metabolic dysfunction in obesity.

YEAR IN REVIEW

Obesity in 2010: The future of obesity medicine: where do we go from here?

Suzanne M. Wright & Louis J. Aronne

doi:10.1038/nrendo.2010.231

Nature Reviews Endocrinology 7, 69-70 (2011)

PERSPECTIVES

Slow food, fast food and the control of food intake

Cees de Graaf & Frans J. Kok

doi:10.1038/nrendo.2010.41

Nature Reviews Endocrinology 6, 290-293 (2010)

In this Perspective, De Graaf and Kok argue that two elements of contemporary eating that facilitate a high energy intake, namely a high eating rate and distraction of attention from eating, undermine the body's capacity to regulate its energy intake at healthy levels because they impair the congruent association between sensory signals during eating and the metabolic consequences after ingestion.

NEWS & VIEWS

Gastrointestinal hormones: Uroguanylin—a new gut-derived weapon against obesity?

Gema Frühbeck

doi:10.1038/nrendo.2011.206

Nature Reviews Endocrinology 8, 5-6 (2012)

Obesity: To be obese—does it matter if you are metabolically healthy?

Antony D. Karelis

doi:10.1038/nrendo.2011.181

Nature Reviews Endocrinology 7, 699-700 (2011)

Obesity: Cure obesity: sleep more, eat out less and turn down the heat?

Hideo Makimura

doi:10.1038/nrendo.2011.55

Nature Reviews Endocrinology 7, 318-319 (2011)

Obesity: Lorcaserin—not a new weapon in the battle with appetite

Jason C. G. Halford

doi:10.1038/nrendo.2010.193

Nature Reviews Endocrinology 6, 663-664 (2010)

Obesity: Maintenance of weight loss: setting our goals higher

George A. Bray

doi:10.1038/nrendo.2010.172

Nature Reviews Endocrinology 6, 657-658 (2010)

Surgery: Bariatric surgery in adolescents—the sooner the better?

Ram Weiss

doi:10.1038/nrendo.2010.1

Nature Reviews Endocrinology 6, 125-126 (2010)

Obesity: Intragastric balloons—a bubble to combat the obesity bubble?

Elisabeth M. H. Mathus-Vliegen

doi:10.1038/nrgastro.2009.214

Nature Reviews Gastroenterology & Hepatology 7, 7-8 (2010)

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