Are we close to defining a metabolomic signature of human obesity? A systematic review of metabolomics studies

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Abstract

Introduction

Obesity is a disorder characterized by a disproportionate increase in body weight in relation to height, mainly due to the accumulation of fat, and is considered a pandemic of the present century by many international health institutions. It is associated with several non-communicable chronic diseases, namely, metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cancer. Metabolomics is a useful tool to evaluate changes in metabolites due to being overweight and obesity at the body fluid and cellular levels and to ascertain metabolic changes in metabolically unhealthy overweight and obese individuals (MUHO) compared to metabolically healthy individuals (MHO).

Objectives

We aimed to conduct a systematic review (SR) of human studies focused on identifying metabolomic signatures in obese individuals and obesity-related metabolic alterations, such as inflammation or oxidative stress.

Methods

We reviewed the literature to identify studies investigating the metabolomics profile of human obesity and that were published up to May 7th, 2019 in SCOPUS and PubMed through an SR. The quality of reporting was evaluated using an adapted of QUADOMICS.

Results

Thirty-three articles were included and classified according to four types of approaches. (i) studying the metabolic signature of obesity, (ii) studying the differential responses of obese and non-obese subjects to dietary challenges (iii) studies that used metabolomics to predict weight loss and aimed to assess the effects of weight loss interventions on the metabolomics profiles of overweight or obese human subjects (iv) articles that studied the effects of specific dietary patterns or dietary compounds on obesity-related metabolic alterations in humans.

Conclusion

The present SR provides state-of-the-art information about the use of metabolomics as an approach to understanding the dynamics of metabolic processes involved in human obesity and emphasizes metabolic signatures related to obesity phenotypes.

Electronic supplementary material

The online version of this article (10.1007/s11306-019-1553-y) contains supplementary material, which is available to authorized users.

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Most cited references 153

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Recent advances in the relationship between obesity, inflammation, and insulin resistance.

Jean-Philippe Bastard, Mustapha Maachi, Claire Lagathu … (2006)

It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines. Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are overproduced during obesity, including leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha is overproduced in adipose tissue of several rodent models of obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of cardiovascular complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by triggering different key steps in the insulin signalling pathway. In rodents, resistin can induce insulin resistance, while its implication in the control of insulin sensitivity is still a matter of debate in humans. Adiponectin is highly expressed in WAT, and circulating adiponectin levels are decreased in subjects with obesity-related insulin resistance, type 2 diabetes and coronary heart disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid oxidation in skeletal muscle. In addition, adiponectin counteracts the pro-inflammatory effects of TNF-alpha on the arterial wall and probably protects against the development of arteriosclerosis. In obesity, the pro-inflammatory effects of cytokines through intracellular signalling pathways involve the NF-kappaB and JNK systems. Genetic or pharmacological manipulations of these effectors of the inflammatory response have been shown to modulate insulin sensitivity in different animal models. In humans, it has been suggested that the improved glucose tolerance observed in the presence of thiazolidinediones or statins is likely related to their anti-inflammatory properties. Thus, it can be considered that obesity corresponds to a sub-clinical inflammatory condition that promotes the production of pro-inflammatory factors involved in the pathogenesis of insulin resistance.

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Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies.

Marianne U. Jakobsen, Eilis J O'Reilly, Berit L. Heitmann … (2009)

Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.

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Multicenter, placebo-controlled trial of lorcaserin for weight management.

Steven Smith, Neil Weissman, Christen Anderson … (2010)

Lorcaserin is a selective serotonin 2C receptor agonist that could be useful in reducing body weight. In this double-blind clinical trial, we randomly assigned 3182 obese or overweight adults (mean body-mass index [the weight in kilograms divided by the square of the height in meters] of 36.2) to receive lorcaserin at a dose of 10 mg, or placebo, twice daily for 52 weeks. All patients also underwent diet and exercise counseling. At week 52, patients in the placebo group continued to receive placebo but patients in the lorcaserin group were randomly reassigned to receive either placebo or lorcaserin. Primary outcomes were weight loss at 1 year and maintenance of weight loss at 2 years. Serial echocardiography was used to identify patients in whom valvulopathy (as defined by the Food and Drug Administration) developed. At 1 year, 55.4% of patients (883 of 1595) receiving lorcaserin and 45.1% of patients (716 of 1587) receiving placebo remained in the trial; 1553 patients continued into year 2. At 1 year, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group had lost 5% or more of their body weight (P<0.001), corresponding to an average loss of 5.8+/-0.2 kg with lorcaserin and 2.2+/-0.1 kg with placebo during year 1 (P<0.001). Among the patients who received lorcaserin during year 1 and who had lost 5% or more of their baseline weight at 1 year, the loss was maintained in more patients who continued to receive lorcaserin during year 2 (67.9%) than in patients who received placebo during year 2 (50.3%, P<0.001). Among 2472 patients evaluated at 1 year and 1127 evaluated at 2 years, the rate of cardiac valvulopathy was not increased with the use of lorcaserin. Among the most frequent adverse events reported with lorcaserin were headache, dizziness, and nausea. The rates of serious adverse events in the two groups were similar. In conjunction with behavioral modification, lorcaserin was associated with significant weight loss and improved maintenance of weight loss, as compared with placebo. (Funded by Arena Pharmaceuticals; ClinicalTrials.gov number, NCT00395135.) 2010 Massachusetts Medical Society

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Author and article information

Contributors

Angel Gil:

ORCID: http://orcid.org/0000-0001-7663-0939

+34 695 466922 , agil@ugr.es

Journal

Journal ID (nlm-ta): Metabolomics

Journal ID (iso-abbrev): Metabolomics

Title: Metabolomics

Publisher: Springer US (New York )

ISSN (Print): 1573-3882

ISSN (Electronic): 1573-3890

Publication date (Electronic): 13 June 2019

Publication date PMC-release: 13 June 2019

Publication date (Print): 2019

Volume: 15

Issue: 6

Electronic Location Identifier: 93

Affiliations

[1 ]ISNI 0000 0004 1936 8921, GRID grid.5510.1, Faculty of Medicine, Department of Nutrition, , University of Oslo, ; Oslo, Norway

[2 ]ISNI 0000 0000 9542 2193, GRID grid.410549.d, Norwegian Veterinary Institute, ; Oslo, Norway

[3 ]ISNI 0000 0004 0477 2585, GRID grid.411095.8, LMU - Ludwig-Maximilians-Universität München, Division of Metabolic and Nutritional Medicine, , Dr. von Hauner Children’s Hospital, University of Munich Medical Center, ; Munich, Germany

[4 ]Institute of Epidemiology, Helmholtz Zentrum München–German Research Centre for Environmental Health, Neuherberg, Germany

[5 ]ISNI 0000000121678994, GRID grid.4489.1, Department of Biochemistry and Molecular Biology II, , Institute of Nutrition and Food Technology “José Mataix, Centre for Biomedical Research, University of Granada”, ; Granada, Spain

[6 ]Instituto de Investigación Biosanitaria ibs-Granada, Granada, Spain

[7 ]Physiopathology of Obesity and Nutrition Networking Biomedical Research Centre (CIBEROBN), Madrid, Spain

Author information

Oscar Daniel Rangel-Huerta http://orcid.org/0000-0001-8585-0108

Belén Pastor-Villaescusa http://orcid.org/0000-0003-0817-6804

Angel Gil http://orcid.org/0000-0001-7663-0939

Article

Publisher ID: 1553

DOI: 10.1007/s11306-019-1553-y

PMC ID: 6565659

PubMed ID: 31197497

SO-VID: d92a4eb2-ed5b-4798-92b8-bc8404a99e5a

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 18 December 2018

Date accepted : 1 June 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100010665, H2020 Marie Skłodowska-Curie Actions;

Award ID: 609020

Award Recipient : Oscar Daniel Rangel-Huerta

Funded by: FundRef http://dx.doi.org/10.13039/100008052, Fundación Alfonso Martín Escudero;

Award ID: postdoctoral researchers at foreign universities

Award Recipient : Belén Pastor-Villaescusa

Custom metadata

ScienceOpen disciplines: Molecular biology

Keywords: metabolomics,obesity and overweight,metabolic profiling,weight loss,dietary intervention

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ScienceOpen disciplines: Molecular biology

Keywords: metabolomics, obesity and overweight, metabolic profiling, weight loss, dietary intervention

Are we close to defining a metabolomic signature of human obesity? A systematic review of metabolomics studies

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Abstract

Introduction

Objectives

Methods

Results

Conclusion

Electronic supplementary material

Related collections

Karger: Nutrition and Dietetics

Most cited references 153

Recent advances in the relationship between obesity, inflammation, and insulin resistance.

Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies.

Multicenter, placebo-controlled trial of lorcaserin for weight management.

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