Obesity | Nature Medicine

Comment | 03 January 2024

Inequalities in the provision of GLP-1 receptor agonists for the treatment of obesity

GLP-1 receptor agonists are effective treatments for obesity but are less accessible worldwide than pharmacological treatments for diabetes, reflecting biases and lack of education, and perpetuating health inequalities.

Stephanie W. Waldrop
, Veronica R. Johnson
& Fatima Cody Stanford

Research Highlight | 30 November 2023

Semaglutide offers new route to cardiovascular risk reduction

In people with cardiovascular disease (without diabetes) and overweight or obesity, the GLP-1 receptor agonist semaglutide significantly reduced the risk of major cardiovascular events.

Karen O’Leary

Article
15 October 2023 | Open Access

Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial

In the SURMOUNT-3 trial, once-weekly treatment with tirzepatide was demonstrated to result in clinically meaningful additional weight loss in adults with overweight or obesity following initial successful weight loss of at least 5% body weight with intensive lifestyle intervention.

Thomas A. Wadden
, Ariana M. Chao
& Tammy Forrester

Research Highlight | 21 September 2023

Prescription for a healthy diet

Produce prescriptions improved fruit and vegetable intake, reduced food insecurity and improved biomarkers of cardiometabolic health, according to a large, retrospective, US-based study.

Karen O’Leary

News & Views | 21 September 2023

A revolution in obesity treatment

Mounting evidence, including the recent (and unprecedented) phase 2 data on retatrutide, supports a role for incretin hormone agonists in treating obesity. But with great power comes great responsibility.

Ildiko Lingvay
& Shubham Agarwal

Article
17 April 2023 | Open Access

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

Modeling analysis from the Global Dietary Database estimated that 70% of new global cases of type 2 diabetes are attributable to suboptimal intake of 11 dietary factors, with substantial differences in dietary risks across world regions and nations.

Meghan O’Hearn
, Laura Lara-Castor
& Rubina Hakeem

Article | 06 April 2023

Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial

Comparison of intermittent fasting plus early time-restricted eating (iTRE) to calorie restriction, as well as standard care, in adults at risk of type 2 diabetes in a three-arm randomized controlled study demonstrated that iTRE was associated with greater improvements in postprandial glucose metabolism at 6 months.

Xiao Tong Teong
, Kai Liu
& Leonie K. Heilbronn

Research Highlight | 30 January 2023

Benefits of bariatric surgery prevail

Despite concerns that bariatric surgery may increase patients’ risk of esophageal or gastric cancers, a large retrospective study offers reassurance that this is not the case.

Karen O’Leary

Article
10 October 2022 | Open Access

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

Results from the STEP 5 trial, testing semaglutide as an adjunct to behavioral interventions in adults with overweight or obesity, demonstrate sustained weight loss over a period of 104 weeks.

W. Timothy Garvey
, Rachel L. Batterham
& Sean Wharton

Article | 25 July 2022

Genetic risk score enhances the risk prediction of severe obesity in adult survivors of childhood cancer

A report from large cohorts of adult survivors of childhood cancer demonstrates that genetic risk scores improve the risk prediction of developing severe obesity, providing opportunities for surveillance and mitigation interventions

Yadav Sapkota
, Weiyu Qiu
& Yutaka Yasui

Research Highlight | 27 June 2022

An anti-obesity drug from the diabetes toolbox

In a phase 3 study, the diabetes drug tirzepatide brought about substantial and sustained weight reduction in adults with obesity.

Karen O’Leary

Article | 04 October 2021

Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce

Studies in mature human adipocytes demonstrate that obesity and hyperinsulinemia can induce reentry into the cell cycle and induce senescence.

Qian Li
, Carolina E. Hagberg
& Kirsty L. Spalding

Research Highlight | 29 July 2021

Obesity genes open new avenues of research

A large-scale genetic sequencing study reveals a potential new therapeutic target in obesity.

Karen O’Leary

Article | 27 May 2021

Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort

Analysis of mutations in MC4R and associated anthropometric phenotypes in the ALSPAC birth cohort reveals a prevalence of heterozygous loss of function of 0.30% and provides evidence that these mutations are associated with substantial excess adiposity in early life.

Kaitlin H. Wade
, Brian Y. H. Lam
& Stephen O’Rahilly

News & Views | 15 April 2021

The STEP 1 trial for weight loss: a step change in treating obesity?

A new trial shows that adding the glucagon‐like peptide 1 analog semaglutide to diet and exercise leads to weight loss.

Amanda I. Adler

News & Views | 01 February 2021

Impact of carbohydrates, fat and energy density on energy intake

People on low-fat, low-energy-density diets have lower ad libitum energy intake than that of those on high-fat, high-energy-density diets.

R. James Stubbs

Article | 21 January 2021

Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake

In an inpatient, randomized controlled crossover trial, participants consumed 550–700 kcal day⁻¹ fewer calories when following a plant-based, low-fat diet with a high glycemic load compared with an animal-based, low-carbohydrate diet with a low glycemic load; weight loss was comparable between the two diets and there were no significant differences in hunger or enjoyment of the meals.

Kevin D. Hall
, Juen Guo
& Stephanie T. Chung

Letter | 04 January 2021

Brown adipose tissue is associated with cardiometabolic health

Retrospective analysis of ¹⁸F-FDG PET/CT scans from over 50,000 patients reveals correlations between presence of brown adipose tissue and lower odds of having cardiometabolic conditions, such as type 2 diabetes, cardiovascular disease and hypertension.

Tobias Becher
, Srikanth Palanisamy
& Paul Cohen

News & Views | 15 October 2020

Weight loss is the major player in bariatric surgery benefits

A metabolic study comparing people who lost weight through dieting or through bariatric surgery shows that the effects on diabetes are due to weight loss.

John Wilding

Article
20 April 2020 | Open Access

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Damaris K. Kinyoki
, Jennifer M. Ross
& Simon I. Hay

Article | 23 March 2020

Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans

A proof-of-concept clinical study shows that perturbations to the gut microbiome affect nutrient absorption in humans.

Alessio Basolo
, Maximilian Hohenadel
& Jonathan Krakoff

Consensus Statement
04 March 2020 | Open Access

Joint international consensus statement for ending stigma of obesity

Francesco Rubino
, Rebecca M. Puhl
& John B. Dixon

Letter | 09 September 2019

Adipose lipid turnover and long-term changes in body weight

Long-term changes in body weight are determined by rates of adipose lipid turnover.

P. Arner
, S. Bernard
& K. L. Spalding

Letter | 09 September 2019

Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease

Analysis of the UK Biobank reveals new genetic loci associated with estimated visceral adipose tissue (VAT) mass, and suggests that VAT is potentially an independent risk factor for various cardiovascular and metabolic diseases, such as hypertension and type 2 diabetes.

Torgny Karlsson
, Mathias Rask-Andersen
& Åsa Johansson

Letter | 01 July 2019

Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study

Supplementation with Akkermansia muciniphila, a gut microbe previously associated with metabolic health in preclinical models, is safe and well tolerated in humans and may improve metabolic parameters in overweight and obese patients.

Clara Depommier
, Amandine Everard
& Patrice D. Cani

Article | 06 March 2019

Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity

Defects in the regulation of leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity.

Olof S. Dallner
, Jill M. Marinis
& Jeffrey M. Friedman

Letter | 04 March 2019

IL1R1 is required for celastrol’s leptin-sensitization and antiobesity effects

IL1R1 is a gatekeeper for celastrol’s metabolic actions.

Xudong Feng
, Dongxian Guan
& Umut Ozcan

Article | 12 November 2018

Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade

Obesity promotes tumor growth yet simultaneously increases susceptibility to PD-1-targeted cancer immunotherapy.

Ziming Wang
, Ethan G. Aguilar
& Arta M. Monjazeb

Article | 25 June 2018

Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women

Metabolic activity of specific human gut microorganisms contributes to liver steatosis in obese women.

Lesley Hoyles
, José-Manuel Fernández-Real
& Marc-Emmanuel Dumas

News & Views | 06 June 2018

Reducing diabetes risk at an early age

A large retrospective study involving 62,565 Danish men shows that those who have been overweight in childhood have a lower risk of having type 2 diabetes in adulthood if they had remission of overweight before 13 years of age.

Daniel S. Hsia
& Steven B. Heymsfield

Article | 21 May 2018

An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling

Inhibition of immune cell–derived acetylcholine synthesis or of its signaling via CHRNA2 in beige adipocytes reduces thermogenesis and exacerbates diet-induced obesity, suggesting a new mode of immuno–fat communication in energy metabolism.

Heejin Jun
, Hui Yu
& Jun Wu

Brief Communication | 07 May 2018

MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency

Treatment with setmelanotide, a new-generation MC4R agonist, provides durable weight loss in hyperphagic, leptin receptor–deficient patients, suggesting a pharmacological avenue to treat patients with various MC4R pathway defects.

Karine Clément
, Heike Biebermann
& Peter Kühnen

Editorial | 07 December 2017

Cutting out the liver fat

Better animal models of nonalcoholic steatohepatitis are needed to more fully understand the disease and to identify potential new therapeutic treatments for this increasingly common condition.

News & Views | 07 December 2017

Fattening the role of Ca²⁺ cycling in adaptive thermogenesis

A new study shows that deleting uncoupling protein 1 activates Ca²⁺ cycling thermogenesis within beige fat, protecting mice against cold-induced hypothermia and dysglycemia following diet-induced obesity.

Daniel Gamu
& A Russell Tupling

News & Views | 01 November 2017

Macrophages dispose of catecholamines in adipose tissue

Recent research has identified sympathetic neuron–associated macrophages in adipose tissue that take up and degrade catecholamines released from neurons. Obesity and aging enhance this system, decreasing responses to cold stress and starvation.

Michael P Czech

News & Views | 01 October 2017

GDF15 and energy balance: homing in on a mechanism

Three recent studies in mice have identified a specific receptor, GFRAL, for the known anorectic peptide GDF15. The finding increases mechanistic understanding of its effect and paves the way for the development of novel anti-obesity therapeutics.

Irene Cimino
, Anthony P Coll
& Giles S H Yeo

Article | 28 August 2017

GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates

GDF15 has potent anti-obesity effects, but its receptor was unknown. GFRAL has now been identified as the receptor and mediates GDF15's effects through central actions in the hindbrain.

Shannon E Mullican
, Xiefan Lin-Schmidt
& Shamina M Rangwala

Article | 28 August 2017

GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand

GDF15 has potent anti-obesity effects, but its receptor was unknown. GFRAL has now been identified as the receptor that mediates GDF15's effects via central actions in the hindbrain.

Linda Yang
, Chih-Chuan Chang
& Sebastian Beck Jørgensen

Perspective | 01 July 2017

Insulin action and resistance in obesity and type 2 diabetes

In this Perspective, Michael Czech presents evidence for whether hyperinsulinemia occurs before insulin resistance upon overfeeding or high-fat diet feeding, or whether insulin resistance causes hyperinsulinemia, thus attempting to delineate the relationship between hyperinsulinemia, obesity and insulin resistance.

Michael P Czech

Article | 19 June 2017

Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention

Composition of gut bacteria and serum metabolites in young, obese individuals is partially restored following weight loss surgery, including Bacteroides thetaiotaomicron, which decreases serum glutamate levels and fat mass gain in mice.

Ruixin Liu
, Jie Hong
& Weiqing Wang

Article | 12 June 2017

Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis

During cold stimulation, cholesterol is converted to bile acids in an alternative pathway. The bile acids then alter the microbiota, which in turn promotes more heat generation.

Anna Worthmann
, Clara John
& Joerg Heeren

News & Views | 06 January 2017

A microbial protein that alleviates metabolic syndrome

A recent study shows that pasteurization of Akkermansia muciniphila enhances the bacterium's ability to reduce fat mass and metabolic syndrome in mice with diet-induced obesity, and that Amuc_1100*, a thermostable outer-membrane protein of A. muciniphila, can reproduce these beneficial effects.

Fernando Forato Anhê
& André Marette

News & Views | 07 September 2016

Obesity: will withaferin win the war?

A new study shows that withaferin A, a steroidal lactone isolated from Withania somnifera, can exert profound metabolic benefits in mice, including body-weight loss, reduced hepatic steatosis and improved glucose control.