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Treatment of Obesity and Its Metabolic Complications

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A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 22917

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Dr. Anna Ferrulli

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1. Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, MI, Italy
2. Clinical Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS Multimedica, 20099 Sesto San Giovanni and Ospedale San Giuseppe, Milan, MI, Italy
Interests: obesity; type 2 diabetes; metabolic diseases; obesity treatment; neuromodulation; eating behavior

Special Issue Information

Dear Colleagues,

Obesity and its main metabolic complications have attained the status of a global pandemic. Despite significant investments into obesity research, its prevalence continues to rise at alarming rates, and it remains an extremely complex phenomenon. In order to counteract its consequences, the obesity epidemic should be strategically tackled at the global level. There is a thus need for novel strategies aimed at treating obesity and preventing the development of complications. From the medical management perspective, pharmacotherapy can help maintain patient compliance, ameliorate obesity-related health risks, and improve quality of life.

Recently, several non-drug therapies have been recently tested in obesity, such as non-invasive neurostimulation, with promising results.

In this Special Issue, we will deepen the current knowledge on available therapeutic strategies to counteract obesity and its complications, but above all, we will highlight future perspectives, with particular emphasis on the treatment of special types of obesity, such as syndromic and monogenic forms of obesity, or sarcopenic obesity. In fact, up to now, the management of genetic obesity only focused on controlling the patient's environment, which involves limiting access to food and the practice of adapted, physical activity.

Articles for this Special Issue will cover: 1. An update on the strategies currently available for the management of obesity and its complications; 2. New promising pharmacological and nonpharmacological targets for the treatment of obesity; 3) Novel strategies for special types of obesity, such as syndromic and monogenic forms of obesity, or sarcopenic obesity; 4) and nutraceutical approaches for treating and preventing obesity.

Dr. Anna Ferrulli
Guest Editor

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Keywords

obesity
pharmacological treatment
obesity complication
neuromodulation
nutraceutical approach
sarcopenic obesity
genetic obesity

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Published Papers (8 papers)

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Research

14 pages, 1693 KiB

Open AccessArticle

Baseline Serum Biomarkers Predict Response to a Weight Loss Intervention in Older Adults with Obesity: A Pilot Study

by David H. Lynch, Blake R. Rushing, Wimal Pathmasiri, Susan McRitchie, Dakota J. Batchek, Curtis L. Petersen, Danae C. Gross, Susan C. J. Sumner and John A. Batsis

Metabolites 2023, 13(7), 853; https://doi.org/10.3390/metabo13070853 - 17 Jul 2023

Cited by 5 | Viewed by 2044

Abstract

Caloric restriction and aerobic and resistance exercise are safe and effective lifestyle interventions for achieving weight loss in the obese older population (>65 years) and may improve physical function and quality of life. However, individual responses are heterogeneous. Our goal was to explore the use of untargeted metabolomics to identify metabolic phenotypes associated with achieving weight loss after a multi-component weight loss intervention. Forty-two older adults with obesity (body mass index, BMI, ≥30 kg/m²) participated in a six-month telehealth-based weight loss intervention. Each received weekly dietitian visits and twice-weekly physical therapist-led group strength training classes with a prescription for aerobic exercise. We categorized responders’ weight loss using a 5% loss of initial body weight as a cutoff. Baseline serum samples were analyzed to determine the variable importance to the projection (VIP) of signals that differentiated the responder status of metabolic profiles. Pathway enrichment analysis was conducted in Metaboanalyst. Baseline data did not differ significantly. Weight loss was 7.2 ± 2.5 kg for the 22 responders, and 2.0 ± 2.0 kg for the 20 non-responders. Mummichog pathway enrichment analysis revealed that perturbations were most significant for caffeine and caffeine-related metabolism (p = 0.00028). Caffeine and related metabolites, which were all increased in responders, included 1,3,7-trimethylxanthine (VIP = 2.0, p = 0.033, fold change (FC) = 1.9), theophylline (VIP = 2.0, p = 0.024, FC = 1.8), paraxanthine (VIP = 2.0, p = 0.028, FC = 1.8), 1-methylxanthine (VIP = 1.9, p = 0.023, FC = 2.2), 5-acetylamino-6-amino-3-methyluracil (VIP = 2.2, p = 0.025, FC = 2.2), 1,3-dimethyl uric acid (VIP = 2.1, p = 0.023, FC = 2.3), and 1,7-dimethyl uric acid (VIP = 2.0, p = 0.035, FC = 2.2). Increased levels of phytochemicals and microbiome-related metabolites were also found in responders compared to non-responders. In this pilot weight loss intervention, older adults with obesity and evidence of significant enrichment for caffeine metabolism were more likely to achieve ≥5% weight loss. Further studies are needed to examine these associations in prospective cohorts and larger randomized trials. Full article

(This article belongs to the Special Issue Treatment of Obesity and Its Metabolic Complications)

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20 pages, 2552 KiB

Open AccessArticle

Metabolomic Study of Aging in fa/fa Rats: Multiplatform Urine and Serum Analysis

by Helena Pelantová, Petra Tomášová, Blanka Šedivá, Barbora Neprašová, Lucia Mráziková, Jaroslav Kuneš, Blanka Železná, Lenka Maletínská and Marek Kuzma

Metabolites 2023, 13(4), 552; https://doi.org/10.3390/metabo13040552 - 12 Apr 2023

Cited by 2 | Viewed by 1694

Abstract

Zucker fatty (fa/fa) rats represent a well-established and widely used model of genetic obesity. Because previous metabolomic studies have only been published for young fa/fa rats up to 20 weeks of age, which can be considered early maturity in male fa/fa rats, the aim of our work was to extend the metabolomic characterization to significantly older animals. Therefore, the urinary profiles of obese fa/fa rats and their lean controls were monitored using untargeted NMR metabolomics between 12 and 40 weeks of age. At the end of the experiment, the rats were also characterized by NMR and LC-MS serum analysis, which was supplemented by a targeted LC-MS analysis of serum bile acids and neurotransmitters. The urine analysis showed that most of the characteristic differences detected in young obese fa/fa rats persisted throughout the experiment, primarily through a decrease in microbial co-metabolite levels, the upregulation of the citrate cycle, and changes in nicotinamide metabolism compared with the age-related controls. The serum of 40-week-old obese rats showed a reduction in several bile acid conjugates and an increase in serotonin. Our study demonstrated that the fa/fa model of genetic obesity is stable up to 40 weeks of age and is therefore suitable for long-term experiments. Full article

(This article belongs to the Special Issue Treatment of Obesity and Its Metabolic Complications)

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14 pages, 1489 KiB

Open AccessArticle

Role of Insulin Resistance as a Mediator of the Relationship between Body Weight, Waist Circumference, and Systolic Blood Pressure in a Pediatric Population

by Simonetta Genovesi, Laura Montelisciani, Marco Giussani, Giulia Lieti, Ilenia Patti, Antonina Orlando, Laura Antolini and Gianfranco Parati

Metabolites 2023, 13(3), 327; https://doi.org/10.3390/metabo13030327 - 23 Feb 2023

Cited by 4 | Viewed by 1854

Abstract

Excess weight and high waist circumference (WC) are associated with increased blood pressure (BP), starting from the pediatric age. Insulin resistance is associated with elevated BP in childhood. The aim of the study was to assess the role of insulin resistance in mediating the relationship between body mass index (BMI), WC, and BP values in a pediatric population referred to a cardio-pediatric center for the presence of one or more cardiovascular risk factors. In 419 children (mean age 10.7 [standard deviation, SD 2.5] years), the following parameters were collected both in basal conditions and after 18.6 (SD 9.3) months of follow-up during which a treatment based on lifestyle and dietary modifications was given: systolic and diastolic BP (SBP and DBP), WC, plasma glucose, and insulin values. The HOMA (Homeostasis Model Assessment)-index was considered as an expression of insulin resistance. At baseline there was a significant correlation between HOMA-index and SBP z-score (β = 0.081, p = 0.003), and insulin resistance was a mediator of the relationship between BMI and SBP z-score (p = 0.015), and between waist circumference to height (WtHr) and SBP z-score (p = 0.008). The effect of BMI z-score modifications on SBP z-score changes from baseline to follow-up was totally mediated by HOMA-index changes (p = 0.008), while HOMA-index only partially mediated the effect of WtHr modifications on SBP z-score changes (p = 0.060). Our study strongly suggests that, in a pediatric population at cardiovascular risk, the HOMA-index is an important mediator of the relationship between BMI, WC and SBP. Full article

(This article belongs to the Special Issue Treatment of Obesity and Its Metabolic Complications)

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21 pages, 2793 KiB

Open AccessArticle

Application of Artificial Neural Networks (ANN) to Elucidate the Connections among Smell, Obesity with Related Metabolic Alterations, and Eating Habit in Patients with Weight Excess

by Fernanda Velluzzi, Andrea Deledda, Mauro Lombardo, Michele Fosci, Roberto Crnjar, Enzo Grossi and Giorgia Sollai

Metabolites 2023, 13(2), 206; https://doi.org/10.3390/metabo13020206 - 30 Jan 2023

Cited by 11 | Viewed by 3300

Abstract

Obesity is a severe health problem linked to an increased risk of comorbidity and mortality and its etiopathogenesis includes genetic, epigenetic, microbiota composition, and environmental factors, such as dietary habits. The olfactory system plays an important role in controlling food intake and meal size, influencing body weight and energy balance. This study aims to identify the connection between olfactory function and clinical and nutritional aspects related to weight excess in a group of 68 patients with overweight or obesity. All participants underwent the evaluation of olfactory function, anthropometric data (weight, height, BMI, waist circumference), clinical data (hypertension, disglycemia, dyslipidemia, metabolic syndrome), and adherence to the Mediterranean diet (Mediterranean Diet Score). A fourth-generation artificial neural network data mining approach was used to uncover trends and subtle associations between variables. Olfactory tests showed that 65% of patients presented hyposmia. A negative correlation was found between olfactory scores and systolic blood pressure, fasting plasma glucose, and triglycerides levels, but a positive correlation was found between olfactory scores and the Mediterranean diet score. The methodology of artificial neural networks and the semantic connectivity map “Auto-Contractive Map” highlighted the underlying scheme of the connections between the variables considered. In particular, hyposmia was linked to obesity and related metabolic alterations and the male sex. The female sex was connected with normosmia, higher adherence to the Mediterranean diet, and normal values of blood pressure, lipids, and glucose levels. These results highlight an inverse correlation between olfactory skills and BMI and show that a normosmic condition, probably because of greater adherence to the Mediterranean diet, seems to protect not only from an excessive increase in body weight but also from associated pathological conditions such as hypertension and metabolic syndrome. Full article

(This article belongs to the Special Issue Treatment of Obesity and Its Metabolic Complications)

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15 pages, 3064 KiB

Open AccessArticle

Effect of Linoleic Acid on Cholesterol Levels in a High-Fat Diet-Induced Hypercholesterolemia Rat Model

by Nurul Adila Azemi, Ahmad Khusairi Azemi, Luqman Abu-Bakar, Vigneswari Sevakumaran, Tengku Sifzizul Tengku Muhammad and Noraznawati Ismail

Metabolites 2023, 13(1), 53; https://doi.org/10.3390/metabo13010053 - 30 Dec 2022

Cited by 16 | Viewed by 3111

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, accounting for almost one-third of all deaths. The risk factors for developing this disease include high levels of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), alongside low levels of high-density lipoprotein (HDL). Dietary linoleic acid has been suggested to reduce these risk factors. This study aims to determine the effects of linoleic acid on cholesterol levels, liver function tests, and structural changes in liver tissue in comparison with fenofibrate in a hypercholesterolemic rat model. Thirty-six male Sprague Dawley rats (150–180 g) were divided into non-hypercholesterolemic and hypercholesterolemic groups. Hypercholesterolemia was induced in the rats by feeding them with a high-fat diet for two weeks. After two weeks, the non-hypercholesterolemic and hypercholesterolemic rats were equally divided into six groups (n = 6): control non-hypercholesterolemic rats, non-hypercholesterolemic rats treated with fenofibrate (60 mg/kg), non-hypercholesterolemic rats treated with linoleic acid (5 mg/kg), control hypercholesterolemic rats, hypercholesterolemic rats treated with fenofibrate (60 mg/kg), and hypercholesterolemic rats treated with linoleic acid (5 mg/kg). The changes in the rats’ body weight, serum lipid profiles, atherogenic indices, and liver function test results were obtained. The rats’ liver tissues were stained for histopathological analysis. The linoleic acid-treated hypercholesterolemic rats exhibited significantly reduced serum TC, TG, LDL, aspartate aminotransferase, and alanine aminotransferase levels, as well as increased HDL levels compared with the control hypercholesterolemic rats. These linoleic acid effects were comparable to those in the fenofibrate-treated hypercholesterolemic rats. In conclusion, linoleic acid possesses early anti-hypercholesterolemic properties, which may be due to the reductions in serum cholesterol levels and mild early structural changes in the liver tissues of hypercholesterolemic rats. Therefore, continued studies on linoleic acid in atherosclerotic and/or obese animal models are suggested. Full article

(This article belongs to the Special Issue Treatment of Obesity and Its Metabolic Complications)

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12 pages, 1038 KiB

Open AccessArticle

The Role of the GH/IGF1 Axis on the Development of MAFLD in Pediatric Patients with Obesity

by Antonella Mosca, Luca Della Volpe, Anna Alisi, Nadia Panera, Giuseppe Maggiore and Andrea Vania

Metabolites 2022, 12(12), 1221; https://doi.org/10.3390/metabo12121221 - 5 Dec 2022

Cited by 3 | Viewed by 1604

Abstract

The anomalies of the Growth Hormone (GH)/Insulin-like Growth Factor-1 (IGF1) axis are associated with a higher prevalence of Metabolic Associated Fatty Liver Disease (MAFLD) and with a more rapid progression towards fibrosis, cirrhosis, and end-stage liver disease. A total of 191 adolescents with obesity [12–18 years] were consecutively enrolled between January 2014 and December 2020 and underwent liver biopsy to diagnose MAFLD severity. In all patients GH, IGF1 and Insulin-like Growth Factor-Binding Protein 3 (IGFBP3) were measured. Patients with inflammation and ballooning have significantly lower values of GH and IGF1 than those without (GH: 5.4 vs. 7.5 ng/mL; IGF1 245 vs. 284 ng/mL, p < 0.05). GH and IGF1 were also negatively correlated with fibrosis’ degree (r = −0.51, p = 0.001, and r = −0.45, p = 0.001, respectively). Only GH correlated with TNF-a (r = −0.29, p = 0.04) and lobular inflammation (r = −0.36, p = 0.02). At multivariate regression, both GH and IGF1 values, after adjustment for age, sex and BMI, were negatively associated with HOMA-IR but above all with fibrosis (GH→β = −2.3, p = 0.001, IGF1→β = −2.8, p = 0.001). Even in the pediatric population, a reduction of GH input in the liver directly promotes development of de novo hepatic lipogenesis, steatosis, fibrosis and inflammation. The possible role of recombinant GH administration in adolescents with obesity and severe MAFLD deserves to be studied. Full article

(This article belongs to the Special Issue Treatment of Obesity and Its Metabolic Complications)

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14 pages, 3040 KiB

Open AccessArticle

5-Aza-2′-Deoxycytidine Regulates White Adipocyte Browning by Modulating miRNA-133a/Prdm16

by Jia Liang, Ying Jia, Huixin Yu, Haijing Yan, Qingyu Shen, Yong Xu, Yana Li and Meizi Yang

Metabolites 2022, 12(11), 1131; https://doi.org/10.3390/metabo12111131 - 17 Nov 2022

Cited by 3 | Viewed by 2153

Abstract

The conversion of white adipocytes into brown adipocytes improves their thermogenesis and promotes energy consumption. Epigenetic modifications affect related genes and interfere with energy metabolism, and these are the basis of new ideas for obesity treatment. Neonatal mice show high levels of DNA hypermethylation in white adipose tissue early in life and low levels in brown adipose tissue. Thus, we considered that the regulation of DNA methylation may play a role in the conversion of white adipose to brown. We observed growth indicators, lipid droplets of adipocytes, brown fat specific protein, and miRNA-133a after treatment with 5-Aza-2′-deoxycytidine. The expression of Prdm16 and Ucp-1 in adipocytes was detected after inhibiting miRNA-133a. The results showed a decrease in total lipid droplet formation and an increased expression of the brown fat specific proteins Prdm16 and Ucp-1. This study indicated that 5-Aza-2′-deoxycytidine promotes white adipocyte browning following DNA demethylation, possibly via the modulation of miR-133a and Prdm16. Full article

(This article belongs to the Special Issue Treatment of Obesity and Its Metabolic Complications)

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37 pages, 4355 KiB

Open AccessArticle

Dynamics of Gut Microbiota and Clinical Variables after Ketogenic and Mediterranean Diets in Drug-Naïve Patients with Type 2 Diabetes Mellitus and Obesity

by Andrea Deledda, Vanessa Palmas, Vitor Heidrich, Michele Fosci, Mauro Lombardo, Giulia Cambarau, Alessio Lai, Marietta Melis, Elisabetta Loi, Andrea Loviselli, Aldo Manzin and Fernanda Velluzzi

Metabolites 2022, 12(11), 1092; https://doi.org/10.3390/metabo12111092 - 10 Nov 2022

Cited by 21 | Viewed by 5791

Abstract

Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is a progressive chronic metabolic disease that has increasingly spread worldwide, enhancing the mortality rate, particularly from cardiovascular diseases (CVD). Lifestyle improvement through diet and physical activity is, together with drug treatment, the cornerstone of T2DM management. The Mediterranean diet (MD), which favors a prevalence of unprocessed vegetable foods and a reduction in red meats and industrial foods, without excluding any food category, is usually recommended. Recently, scientific societies have promoted a very low-calorie ketogenic diet (VLCKD), a multiphasic protocol that limits carbohydrates and then gradually re-introduces them, with a favorable outcome on body weight and metabolic parameters. Indeed, gut microbiota (GM) modifications have been linked to overweight/obesity and metabolic alterations typical of T2DM. Diet is known to affect GM largely, but only a few studies have investigated the effects of VLCKD on GM, especially in T2DM. In this study, we have compared anthropometric, biochemical, lifestyle parameters, the quality of life, and the GM of eleven patients with recently diagnosed T2DM and overweight or obesity, randomly assigned to two groups of six and five patients who followed the VLCKD (KETO) or hypocaloric MD (MEDI) respectively; parameters were recorded at baseline (T0) and after two (T2) and three months (T3). The results showed that VLCKD had more significant beneficial effects than MD on anthropometric parameters, while biochemical improvements did not statistically differ. As for the GM, despite the lack of significant results regarding the alpha and beta diversity, and the Firmicutes/Bacteroidota ratio between the two groups, in the KETO group, a significant increase in beneficial microbial taxa such as Verrucomicrobiota phylum with its members Verrucomicrobiae, Verrucomicrobiales, Akkermansiaceae, and Akkermansia, Christensenellaceae family, Eubacterium spp., and a reduction in microbial taxa previously associated with obesity (Firmicutes and Actinobacteriota) or other diseases (Alistipes) was observed both at T2 and T3. With regards to the MEDI group, variations were limited to a significant increase in Actinobacteroidota phylum at T2 and T3 and Firmicutes phylum at T3. Moreover, a metagenomic alteration linked to some metabolic pathways was found exclusively in the KETO group. In conclusion, both dietary approaches allowed patients to improve their state of health, but VLCKD has shown better results on body composition as well as on GM profile. Full article

(This article belongs to the Special Issue Treatment of Obesity and Its Metabolic Complications)

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