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Metabolic Health and Weight II

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A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 31719

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Dr. Isabel Moreno-Indias

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1. Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, 29010 Málaga, Spain
2. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, 28029 Madrid, Spain
Interests: obesity; adipose tissue; gut microbiota; diet; bariatric surgery
Special Issues, Collections and Topics in MDPI journals

Dr. Carolina GUtiérrez-Repiso

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Guest Editor

Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain
Interests: intestine flora; ruminococcaceae; dysbiosis 4 documents adipose tissues; adipocytes; obese mice 4 documents thyroid function

Special Issue Information

Dear Colleagues,

Obesity and its comorbidities are a global problem. The classic view about the imbalance in what we eat and what we burn is obsolete and needs to be reviewed. Based on the complex network of the body’s metabolism, metabolites have become an essential part of exploring metabolic health and weight. Increasing evidence provides information about the role of a wide range of metabolites in homeostasis, especially, but not only, those from adipose tissue and gut microbiota. Rapid weight variation (increasing as well as decreasing) implies a loss in homeostasis, and the causes are diverse, not only arising from an imbalance. Multiple aspects are implied, with a key role played by adipose tissue and emerging evidence about the implication of gut microbiota. This Special Issue of Metabolites, "Metabolic Health and Weight," will be dedicated to any aspect related to weight maintenance and homeostasis and the implication of metabolites. The topics that will be covered by this Special Issue include, but are not limited to, the identification of metabolites with biological and/or clinical relevance in obesity and its comorbidities, with a special interest in adipose tissue metabolites and metabolites derived from gut microbiota. Weight variations (weight gain and especially weight loss interventions) and their implications for the weight management and metabolic health are particularly of interest. Manuscripts dealing with other pertinent challenging issues are also highly desired.

Dr. Isabel Moreno-Indias
Dr. Carolina GUtiérrez-Repiso
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Research

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16 pages, 3620 KiB

Open AccessArticle

Independent and Interactive Effects of Genetic Background and Sex on Tissue Metabolomes of Adipose, Skeletal Muscle, and Liver in Mice

by Ann E. Wells, William T. Barrington, Stephen Dearth, Nikhil Milind, Gregory W. Carter, David W. Threadgill, Shawn R. Campagna and Brynn H. Voy

Metabolites 2022, 12(4), 337; https://doi.org/10.3390/metabo12040337 - 08 Apr 2022

Viewed by 2316

Abstract

Genetics play an important role in the development of metabolic diseases. However, the relative influence of genetic variation on metabolism is not well defined, particularly in tissues, where metabolic dysfunction that leads to disease occurs. We used inbred strains of laboratory mice to evaluate the impact of genetic variation on the metabolomes of tissues that play central roles in metabolic diseases. We chose a set of four common inbred strains that have different levels of susceptibility to obesity, insulin resistance, and other common metabolic disorders. At the ages used, and under standard husbandry conditions, these lines are not overtly diseased. Using global metabolomics profiling, we evaluated water-soluble metabolites in liver, skeletal muscle, and adipose from A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ mice fed a standard mouse chow diet. We included both males and females to assess the relative influence of strain, sex, and strain-by-sex interactions on metabolomes. The mice were also phenotyped for systems level traits related to metabolism and energy expenditure. Strain explained more variation in the metabolite profile than did sex or its interaction with strain across each of the tissues, especially in liver. Purine and pyrimidine metabolism and pathways related to amino acid metabolism were identified as pathways that discriminated strains across all three tissues. Based on the results from ANOVA, sex and sex-by-strain interaction had modest influence on metabolomes relative to strain, suggesting that the tissue metabolome remains largely stable across sexes consuming the same diet. Our data indicate that genetic variation exerts a fundamental influence on tissue metabolism. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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14 pages, 3385 KiB

Open AccessArticle

Gut Microbiota Metabolism of Bile Acids Could Contribute to the Bariatric Surgery Improvements in Extreme Obesity

by Luis Ocaña-Wilhelmi, Gracia María Martín-Núñez, Patricia Ruiz-Limón, Juan Alcaide, Eduardo García-Fuentes, Carolina Gutiérrez-Repiso, Francisco J. Tinahones and Isabel Moreno-Indias

Metabolites 2021, 11(11), 733; https://doi.org/10.3390/metabo11110733 - 27 Oct 2021

Cited by 10 | Viewed by 2306

Abstract

Bariatric surgery is the only procedure to obtain and maintain weight loss in the long term, although the mechanisms driving these benefits are not completely understood. In the last years, gut microbiota has emerged as one of the drivers through its metabolites, especially secondary bile acids. In the current study, we have compared the gut microbiota and the bile acid pool, as well as anthropometric and biochemical parameters, of patient with morbid obesity who underwent bariatric surgery by two different techniques, namely Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Gut microbiota populations differed after the respective procedures, particularly with respect to the Enterobacteriaceae family. Both techniques resulted in changes in the bile acids pool, but RYGB was the procedure which suffered the greatest changes, with a reduction in most of their levels. Blautia and Veillonella were the two genera that more relationships showed with secondary bile acids, indicating a possible role in their formation and inhibition, respectively. Correlations with the anthropometric and biochemical variables showed that secondary bile acids could have a role in the amelioration of the glucose and HDL-cholesterol levels. Thus, we have observed a possible relationship between the interaction of the bile acids pool metabolized by the gut microbiota in the metabolic improvements obtained by bariatric surgery in the frame of morbid obesity, deserving further investigation in greater cohorts to decipher the role of each bile acid in the homeostasis of the host for their possible use in the development of microbiota-based therapeutics, such as new drugs, postbiotics or probiotics. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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12 pages, 2161 KiB

Open AccessArticle

Osteocalcin Is Independently Associated with C-Reactive Protein during Lifestyle-Induced Weight Loss in Metabolic Syndrome

by Silke Zimmermann, Maria Beatriz Walter Costa, Akash Mathew, Shruthi Krishnan, Jochen G. Schneider, Kirsten Roomp, Berend Isermann and Ronald Biemann

Metabolites 2021, 11(8), 526; https://doi.org/10.3390/metabo11080526 - 09 Aug 2021

Cited by 5 | Viewed by 2448

Abstract

Bone-derived osteocalcin has been suggested to be a metabolic regulator. To scrutinize the relation between osteocalcin and peripheral insulin sensitivity, we analyzed changes in serum osteocalcin relative to changes in insulin sensitivity, low-grade inflammation, and bone mineral density following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). Participants with MetS were randomized to a weight loss program or to a control group. Before and after the 6-month intervention period, clinical and laboratory parameters and serum osteocalcin levels were determined. Changes in body composition were analyzed by dual-energy X-ray absorptiometry (DXA). In participants of the intervention group, weight loss resulted in improved insulin sensitivity and amelioration of inflammation. Increased serum levels of osteocalcin correlated inversely with BMI (r = −0.63; p< 0.001), total fat mass (r = −0.58, p < 0.001), total lean mass (r = −0.45, p < 0.001), C-reactive protein (CRP) (r = −0.37; p < 0.01), insulin (r = −0.4; p < 0.001), leptin (r = −0.53; p < 0.001), triglycerides (r = −0.42; p < 0.001), and alanine aminotransferase (ALAT) (r = −0.52; p < 0.001). Regression analysis revealed that osteocalcin was independently associated with changes in CRP but not with changes in insulin concentration, fat mass, or bone mineral density, suggesting that weight loss-induced higher serum osteocalcin is primarily associated with reduced inflammation. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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16 pages, 6080 KiB

Open AccessArticle

Serum Metabolites Responding in a Dose-Dependent Manner to the Intake of a High-Fat Meal in Normal Weight Healthy Men Are Associated with Obesity

by Ueli Bütikofer, David Burnand, Reto Portmann, Carola Blaser, Flurina Schwander, Katrin A. Kopf-Bolanz, Kurt Laederach, René Badertscher, Barbara Walther and Guy Vergères

Metabolites 2021, 11(6), 392; https://doi.org/10.3390/metabo11060392 - 16 Jun 2021

Cited by 4 | Viewed by 3440

Abstract

Although the composition of the human blood metabolome is influenced both by the health status of the organism and its dietary behavior, the interaction between these two factors has been poorly characterized. This study makes use of a previously published randomized controlled crossover acute intervention to investigate whether the blood metabolome of 15 healthy normal weight (NW) and 17 obese (OB) men having ingested three doses (500, 1000, 1500 kcal) of a high-fat (HF) meal can be used to identify metabolites differentiating these two groups. Among the 1024 features showing a postprandial response, measured between 0 h and 6 h, in the NW group, 135 were dose-dependent. Among these 135 features, 52 had fasting values that were significantly different between NW and OB men, and, strikingly, they were all significantly higher in OB men. A subset of the 52 features was identified as amino acids (e.g., branched-chain amino acids) and amino acid derivatives. As the fasting concentration of most of these metabolites has already been associated with metabolic dysfunction, we propose that challenging normal weight healthy subjects with increasing caloric doses of test meals might allow for the identification of new fasting markers associated with obesity. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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10 pages, 1320 KiB

Open AccessCommunication

Leaky Gut as a Potential Culprit for the Paradoxical Dysglycemic Response to Gastric Bypass-Associated Ileal Microbiota

by Mohammed K. Hankir, Florian Seyfried, Isabel N. Schellinger, Nicolas Schlegel and Tulika Arora

Metabolites 2021, 11(3), 153; https://doi.org/10.3390/metabo11030153 - 08 Mar 2021

Cited by 3 | Viewed by 1840

Abstract

Altered host-intestinal microbiota interactions are increasingly implicated in the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. We previously found, however, that RYGB-associated ileal microbiota can paradoxically impair host glycemic control when transferred to germ-free mice. Here we present complementary evidence suggesting that this could be due to the heightened development of systemic endotoxemia. Consistently, application of ileal content from RYGB-treated compared with sham-operated rats onto Caco-2 cell monolayers compromised barrier function and decreased expression of the barrier-stabilizing proteins claudin-4 and desmoglein-2. Our findings raise the possibility that RYGB-associated ileal microbiota produce and release soluble metabolites which locally increase intestinal permeability to promote systemic endotoxemia-induced insulin resistance, with potential implications for the treatment of RYGB patients who eventually relapse onto type 2 diabetes. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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15 pages, 745 KiB

Open AccessArticle

Molecular Differences Based on Erythrocyte Fatty Acid Profile to Personalize Dietary Strategies between Adults and Children with Obesity

by Iker Jauregibeitia, Kevin Portune, Sonia Gaztambide, Itxaso Rica, Itziar Tueros, Olaia Velasco, Gema Grau, Alicia Martín, Luis Castaño, Anna Vita Larocca, Federica Di Nolfo, Carla Ferreri and Sara Arranz

Metabolites 2021, 11(1), 43; https://doi.org/10.3390/metabo11010043 - 08 Jan 2021

Cited by 10 | Viewed by 2848

Abstract

As the obesity epidemic continues to grow inexorably worldwide, the need to develop effective strategies to prevent and control obesity seems crucial. The use of molecular tools can be useful to characterize different obesity phenotypes to provide more precise nutritional recommendations. This study aimed to determine the fatty acid (FA) profile of red blood cell (RBC) membranes, together with the evaluation of their dietary intake and biochemical parameters, of children and adults with obesity. An observational study was carried out on 196 children (113 with normal weight and 83 with obesity) and 91 adults (30 with normal weight and 61 with obesity). Mature RBC membrane phospholipids were analyzed for FA composition by gas chromatography-mass spectrometry (GC-MS). Dietary habits were evaluated using validated food frequency questionnaires (FFQ). Children with obesity presented higher levels of ω-6 polyunsaturated FAs (mainly linoleic acid, p = 0.01) and lower values of ω-3 FAs (mainly DHA, p < 0.001) compared with adults. Regarding blood biochemical parameters, children with obesity presented lower levels of glucose, LDL cholesterol, and alanine aminotransferase compared with adults with obesity. These lipidomic differences could be considered to provide specific nutritional recommendations for different age groups, based on an adequate fat intake. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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Review

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24 pages, 1456 KiB

Open AccessReview

Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity

by Klaudia Antoniak, Rita Hansdorfer-Korzon, Małgorzata Mrugacz and Katarzyna Zorena

Metabolites 2021, 11(9), 617; https://doi.org/10.3390/metabo11090617 - 11 Sep 2021

Cited by 9 | Viewed by 5096

Abstract

The World Health Organization (WHO) has recognised obesity as one of the top ten threats to human health. Obesity is not only a state of abnormally increased adipose tissue in the body, but also of an increased release of biologically active metabolites. Moreover, obesity predisposes the development of metabolic syndrome and increases the incidence of type 2 diabetes (T2DM), increases the risk of developing insulin resistance, atherosclerosis, ischemic heart disease, polycystic ovary syndrome, hypertension and cancer. The lymphatic system is a one-directional network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells that provides a unidirectional conduit to return filtered arterial and tissue metabolites towards the venous circulation. Recent studies have shown that obesity can markedly impair lymphatic function. Conversely, dysfunction in the lymphatic system may also be involved in the pathogenesis of obesity. This review highlights the important findings regarding obesity related to lymphatic system dysfunction, including clinical implications and experimental studies. Moreover, we present the role of biological factors in the pathophysiology of the lymphatic system and we propose the possibility of a therapy supporting the function of the lymphatic system in the course of obesity. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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13 pages, 1475 KiB

Open AccessReview

Trefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target

by Abdelaziz Ghanemi, Mayumi Yoshioka and Jonny St-Amand

Metabolites 2021, 11(8), 536; https://doi.org/10.3390/metabo11080536 - 12 Aug 2021

Cited by 5 | Viewed by 2375

Abstract

Obesity has its epidemiological patterns continuously increasing. With controlling both diet and exercise being the main approaches to manage the energy metabolism balance, a high-fat (HF) diet is of particular importance. Indeed, lipids have a low satiety potential but a high caloric density. Thus, focusing on pharmacologically targetable pathways remains an approach with promising therapeutic potential. Within this context, trefoil factor family member 2 (Tff2) has been characterized as specifically induced by HF diet rather than low-fat diet. TFF2 has also been linked to diverse neurological mechanisms and metabolic patterns suggesting its role in energy balance. The hypothesis is that TFF2 would be a HF diet-induced signal that regulates metabolism with a focus on lipids. Within this review, we put the spotlight on key findings highlighting this line of thought. Importantly, the hypothetical mechanisms pointed highlight TFF2 as an important contributor to obesity development via increasing lipids intestinal absorption and anabolism. Therefore, an outlook for future experimental activities and evaluation of the therapeutic potential of TFF2 inhibition is given. Indeed, its knockdown or downregulation would contribute to an antiobesity phenotype. We believe this work represents an addition to our understanding of the lipidic molecular implications in obesity, which will contribute to develop therapies aiming to manage the lipidic metabolic pathways including the absorption, storage and metabolism via targeting TFF2-related pathways. We briefly discuss important relevant concepts for both basic and clinical researchers. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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27 pages, 2791 KiB

Open AccessReview

The Role of Gut Microbiota and Its Produced Metabolites in Obesity, Dyslipidemia, Adipocyte Dysfunction, and Its Interventions

by Max S. Z. Zwartjes, Victor E. A. Gerdes and Max Nieuwdorp

Metabolites 2021, 11(8), 531; https://doi.org/10.3390/metabo11080531 - 10 Aug 2021

Cited by 25 | Viewed by 6145

Abstract

Obesity is becoming an increasing problem worldwide and is often, but not invariably, associated with dyslipidemia. The gut microbiota is increasingly linked to cardiovascular disease, nonalcoholic fatty liver disease, and type 2 diabetes mellitus. However, relatively little focus has been attributed to the role of gut-microbiota-derived metabolites in the development of dyslipidemia and alterations in lipid metabolism. In this review, we discuss current data involved in these processes and point out the therapeutic potentials. We cover the ability of gut microbiota metabolites to alter lipoprotein lipase action, VLDL secretion, and plasma triglyceride levels, and its effects on reverse cholesterol transport, adipocyte dysfunction, and adipose tissue inflammation. Finally, the current intervention strategies for treatment of obesity and dyslipidemia is addressed with emphasis on the role of gut microbiota metabolites and its ability to predict treatment efficacies. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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7 pages, 733 KiB

Open AccessBrief Report

IL-6 Receptor Blockade Increases Circulating Adiponectin Levels in People with Obesity: An Explanatory Analysis

by Stephan Wueest, Eleonora Seelig, Katharina Timper, Mark P. Lyngbaek, Kristian Karstoft, Marc Y. Donath, Helga Ellingsgaard and Daniel Konrad

Metabolites 2021, 11(2), 79; https://doi.org/10.3390/metabo11020079 - 29 Jan 2021

Cited by 10 | Viewed by 1663

Abstract

Human obesity is associated with decreased circulating adiponectin and elevated leptin levels. In vitro experiments and studies in high fat diet (HFD)-fed mice suggest that interleukin-6 (IL-6) may regulate adiponectin and leptin release from white adipose tissue (WAT). Herein, we aimed to investigate whether IL-6 receptor blockade affects the levels of circulating adiponectin and leptin in obese human individuals. To this end, serum samples collected during a multicenter, double-blind clinical trial were analyzed. In the latter study, obese human subjects with or without type 2 diabetes were randomly assigned to recurrent placebo or intravenous tocilizumab (an IL-6 receptor antibody) administration during a 12-week exercise training intervention. Twelve weeks of tocilizumab administration (in combination with exercise training) trend wise enhanced the decrease in circulating leptin levels (−2.7 ± 8.2% in the placebo vs. −20.6 ± 5.6% in tocilizumab, p = 0.08) and significantly enhanced the increase in circulating adiponectin (3.4 ± 3.7% in the placebo vs. 27.0 ± 6.6% in tocilizumab, p = 0.01). In addition, circulating adiponectin levels were negatively correlated with the homeostatic model assessment of insulin resistance (HOMA-IR), indicating that increased adiponectin levels positively affect insulin sensitivity in people with obesity. In conclusion, IL-6 receptor blockade increases circulating adiponectin levels in people with obesity. Full article

(This article belongs to the Special Issue Metabolic Health and Weight II)

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