medtigo Journal of Medicine

| Volume 3, Issue 1

Chemobiology of Obesity and Advances in Bariatrics: A Systematic Review

Author Affiliations

medtigo J Med. |
Date - Received: Feb 03, 2025,
Accepted: Feb 05, 2025,
Published: Feb 21, 2025.

https://doi.org/10.63096/medtigo30623130

Abstract

Background: Obesity is a complex metabolic disorder with significant global health implications. Its pathophysiology is deeply rooted in chemobiological processes involving adipose tissue dysfunction, hormonal imbalances, and inflammatory pathways. Recent advances in bariatric research have expanded beyond surgical interventions to include pharmacological and molecular innovations aimed at addressing obesity at a biochemical level.
Objectives: This review explores the chemobiology of obesity, highlighting key molecular and biochemical mechanisms underlying adipogenesis, energy metabolism, and inflammation. Additionally, it examines recent innovations in bariatric research, including emerging pharmacotherapies, minimally invasive procedures, and metabolic-targeted interventions.
Methods: A systematic search was conducted across major databases (PubMed, Scopus, Web of Science, Embase) for studies published between 2010 and 2024. The review adhered to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, and studies were included if they met predefined inclusion criteria. Data were extracted from randomized controlled trials, observational studies, and systematic reviews. Risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs) and the risk of bias in non-randomized studies of interventions (ROBINS-I) tool for non-randomized studies. Data were synthesized narratively, with a meta-analysis conducted for studies with comparable methodologies.
Results: The review identified key chemobiological mechanisms implicated in obesity, including dysregulated leptin-ghrelin signaling, chronic low-grade inflammation, and altered adipokine profiles. Innovations in bariatric research were categorized into three main domains: (1) pharmacological therapies targeting glucagon-like peptide-1 (GLP-1) receptors, lipolysis, and metabolic pathways; (2) minimally invasive endoscopic and device-assisted interventions; and (3) novel genetic and microbiome-based strategies. Evidence suggests that integrating these approaches may enhance long-term weight management and metabolic outcomes.
Conclusion: Understanding the chemobiological underpinnings of obesity is crucial for developing more effective and sustainable interventions. The landscape of bariatric research is rapidly evolving, with promising advancements that extend beyond traditional surgical approaches. Further interdisciplinary research is needed to optimize these innovations and improve patient outcomes.

Keywords

Obesity, Chemobiology, Bariatric research, Metabolic pathways, Pharmacotherapy, Adipokines, Energy metabolism, Innovative interventions.

Introduction

A body mass index (BMI Kg/m2) of 30 or greater is classified as obese, with further subdivisions based on degree: Class I (BMI 30.0-34.9), Class II (BMI 35.0-39.9), and Class III (BMI ≥ 40.0), also known as morbid obesity. Nearly 1 in 3 adults (30.7%) worldwide are overweight, more than 2 in 5 adults (42.4%) are obese and about 1 in 11 adults (9.2%) have severe obesity (National institute of diabetes and digestive and kidney disease (NIDDK)).

This review explores the intricate bio-mechanisms, chemobiology, and epigenetics underlying obesity. It further explores the molecular pathophysiology pathways, insulin resistance, and the role of adipokines in energy metabolism and metabolic dysregulation. It interrogates how the thermogenic functions of brown and beige adipose tissues can be manipulated as potential therapeutic targets for obesity management. Traditional approaches to managing obesity remain cornerstones of treatment. These traditional approaches include dietary modifications, physical activity, behavioral therapy, and pharmacotherapy. However, the persistence of high obesity rates worldwide highlights the need for more effective and innovative solutions. This review provides valuable insights into the chemobiology of obesity, as well as novel research and emerging therapeutic interventions.

Study justification:
The chemobiology of obesity is a complex and evolving field of study. While significant progress has been made in understanding the underlying mechanisms of obesity, it is not fully understood.[1] Obesity prevalence has risen dramatically over the past few decades, making it a significant public health issue worldwide.[2] Central to the pathophysiology of obesity is the dysregulation of energy balance, adipose tissue function, and insulin signaling, which are influenced by various molecular mechanisms.[1] Despite dietary modifications, physical activity, behavioral therapy, and pharmacotherapy, obesity has emerged as a global epidemic. There is, however, a potential for advanced research in bariatrics.

Research questions:

  • What are the key chemobiological mechanisms underlying obesity, including adipogenesis, energy metabolism, and inflammatory pathways?
  • How do emerging pharmacological interventions, such as (GLP-1) receptor agonists and metabolic modulators, contribute to obesity management?
  • What are the latest advancements in minimally invasive bariatric procedures, and how do they compare to traditional surgical approaches in terms of efficacy and safety?
  • How do genetic, microbiome-based, and other novel therapeutic strategies influence long-term weight management and metabolic health in obesity?

Study aims:

  • To explore the chemobiological mechanisms underlying obesity, including adipogenesis, energy metabolism, and inflammatory pathways.
  • To evaluate recent pharmacological advancements targeting metabolic pathways in obesity management.
  • To review and compare emerging minimally invasive and surgical bariatric interventions in terms of efficacy, safety, and long-term outcomes.
  • To examine the potential role of genetic, microbiome-targeted, and other innovative therapies in obesity treatment and management.

Study objectives:

  • To analyze the biochemical and molecular mechanisms contributing to obesity pathophysiology, including hormonal imbalances and inflammatory responses.
  • To assess the effectiveness of GLP-1 receptor agonists, lipolysis modulators, and other pharmacotherapies in promoting weight loss and metabolic health.
  • To systematically review clinical evidence on novel minimally invasive bariatric procedures and compare their outcomes with traditional surgical approaches.
  • To investigate the impact of genetic predisposition, gut microbiota alterations, and epigenetic factors on obesity and evaluate their potential as therapeutic targets.

Literature review:
Obesity is a multifactorial disorder characterized by excessive adipose tissue accumulation due to a complex interplay between genetic, metabolic, hormonal, and environmental factors. At the molecular level, obesity is driven by dysregulated energy homeostasis, hormonal imbalances, and chronic low-grade inflammation.[3]

The expansion of adipose tissue in obesity is regulated by key transcription factors such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT/enhancer-binding proteins (C/EBPs), which control adipocyte differentiation and lipid storage.[4] Leptin and ghrelin, key hormones governing appetite and metabolism, exhibit dysregulation in obesity. Leptin resistance, characterized by impaired hypothalamic response to leptin, contributes to increased food intake and weight gain.[5] As noted by Garfield et al.[4] in their study, obesity is associated with chronic low-grade inflammation, mediated by increased production of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP). This inflammatory state exacerbates insulin resistance and metabolic dysfunction.

The treatment landscape of obesity has expanded beyond lifestyle interventions to include targeted pharmacotherapies that modulate metabolic pathways. As Wong et al.[6] and Wilding et al.[7] put it, glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide and tirzepatide, have shown significant efficacy in promoting weight loss by reducing appetite and enhancing insulin sensitivity. Drugs targeting lipid metabolism, such as fatty acid synthase (FASN) inhibitors and AMP-activated protein kinase (AMPK) activators, are emerging as potential therapies for obesity.[6,8]

Recent studies by Wong et al.[6] and Meyers et al.[8] have investigated synergistic effects of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) co-agonists, offering improved metabolic control and weight reduction. Traditional bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), remains the most effective long-term intervention for severe obesity.[1]

Importantly, recent advancements have introduced less invasive and reversible procedures. Vagal nerve stimulation (VNS) is being explored as a non-surgical approach to modulate appetite and metabolism. Procedures such as endoscopic sleeve gastroplasty (ESG) and intragastric balloon placement offer effective weight loss with reduced surgical risks.[1,9,10]

Comprehensive studies by Chen et al.[11] highlight the gut microbiome as a key regulator of metabolic health in obesity. Alterations in gut microbial composition influence short-chain fatty acid production, energy extraction, and systemic inflammation.[11] Furthermore, fecal microbiota transplantation (FMT) and probiotic interventions are being investigated as potential obesity treatments, and there are advances in gene editing (CRISPR-Cas9) and epigenetic modulation that may offer future personalized obesity interventions.[11]

In conclusion, the chemobiology of obesity is a rapidly evolving field, with increasing emphasis on molecular and metabolic mechanisms. Innovations in bariatric research, including pharmacotherapies, minimally invasive procedures, and microbiome-based therapies, provide promising alternatives to traditional approaches. Future research should focus on personalized treatment strategies integrating these advancements for improved long-term outcomes.

Methodology

Study design: This research follows a systematic review design, adhering to the PRISMA guidelines to ensure comprehensive, transparent, and reproducible results. The review aims to identify, evaluate, and synthesize existing studies related to the chemobiological mechanisms of obesity and innovations in bariatric research (Figure 1).

PRISMA flow chart of article identification, screening and data selection process

Figure 1: PRISMA flow chart of article identification, screening, and data selection process

Search strategy: A systematic search was conducted across multiple electronic databases, including PubMed, Scopus, Web of Science, and Embase, for relevant articles published from 2010 to 2024. The following keywords and Medical Subject Headings (MeSH) terms were used:

  • Obesity (e.g., “adipogenesis,” “energy metabolism,” “hormonal dysregulation”)
  • Chemobiology (e.g., “inflammatory pathways,” “metabolic dysfunction”)
  • Bariatrics (e.g., “GLP-1 receptor agonists,” “minimally invasive procedures,” “bariatric surgery outcomes”)
  • Genetic and Microbiome Interventions (e.g., “genetic predisposition,” “gut microbiome,” “epigenetic factors in obesity”)

The search was limited to studies published in English and included clinical trials, systematic reviews, and meta-analyses. Studies that focused on pediatric obesity, non-peer-reviewed articles, and non-relevant topics were excluded.

Inclusion criteria:

  • Peer-reviewed clinical trials, systematic reviews, meta-analyses, and observational studies.
  • Studies investigating biochemical mechanisms, pharmacological treatments, and surgical interventions in obesity.
  • Studies on genetic, microbiome-targeted, and other novel therapies for obesity management.

Exclusion criteria:

  • Pediatric obesity studies.
  • Non-peer-reviewed articles, opinion pieces, and editorials.
  • Studies not providing data on biochemical mechanisms or clinical outcomes relevant to obesity management.

Data extraction and synthesis: Two independent reviewers extracted key data from the eligible studies using a standardized data extraction form. The following data were recorded for each study:

  • Study characteristics (author, year of publication, study design, sample size)
  • Biochemical mechanisms (e.g., involvement of PPAR-γ, leptin resistance, inflammatory markers)
  • Pharmacological interventions (e.g., GLP-1 receptor agonists, metabolic modulators)
  • Bariatric procedures (e.g., minimally invasive vs. traditional surgery, clinical outcomes)
  • Emerging therapies (e.g., microbiome-based therapies, genetic interventions)
  • Study quality and risk of bias (using the Cochrane Risk of Bias Tool for randomized trials and the ROBINS-I tool for non-randomized studies).

Data synthesis: Data were synthesized narratively, categorizing findings according to the key research themes: Chemobiology of obesity, pharmacological innovations, surgical and minimally invasive bariatric procedures, and emerging genetic and microbiome therapies. When possible, quantitative results from studies with comparable data were pooled for a meta-analysis.

Risk of bias and quality assessment: Each included study was assessed for methodological quality and risk of bias. RCTs were evaluated using the Cochrane Risk of Bias Tool, which includes domains such as selection bias, performance bias, detection bias, and reporting bias. Non-randomized studies were assessed using the ROBINS-I tool, which examines bias in confounding, selection of participants, and measurement of outcomes.

Data analysis: Descriptive analysis was performed for all studies included in the review. Quantitative data were extracted for studies reporting mean weight loss, glycemic control, and safety outcomes from pharmacological and surgical interventions. For studies with sufficiently similar methodologies, a meta-analysis was conducted using the random effects model. The primary measures were weight loss, improvement in metabolic health markers, and complication rates.

Ethical considerations: The study adhered strictly to the General Data Protection Regulation law (GDPR). All included studies were assessed for ethical compliance, and only research adhering to institutional and international ethical guidelines was considered.

Results

Category Key findings Implications
Biochemical mechanisms Dysregulated adipogenesis, hormonal imbalances, chronic inflammation Highlights metabolic targets for intervention
Pharmacological therapies GLP-1 receptor agonists, dual-agonist therapies, metabolic modulators Effective in weight loss, emerging as alternatives to surgery
Minimally invasive procedures Endoscopic sleeve gastroplasty (ESG), intragastric balloons, vagus nerve stimulation (VNS) Safe alternatives to surgery with moderate weight loss
Emerging research Gut microbiota, gene therapy, epigenetics Potential for personalized obesity treatment

Table 1: Summary of key findings

    Data charting table Relevant selected studies      
Study Authors & Year Objective Key Findings Intervention Type Sample Size Outcome Measures
1 Lopez-Nava et al.[12] Evaluate endoscopic sleeve gastroplasty (ESG) ESG led to significant weight loss (18-20% TWL) at 24 months Endoscopic 248 Total weight loss (TWL), safety profile
2 Abu Dayyeh et al.[13] Assess impact of ESG on gastric emptying Delayed gastric emptying, reduced appetite, significant weight loss Endoscopic 25 Gastric emptying time, weight reduction
3 Vargas et al.[14] Compare gastric emptying post-surgical vs. endoscopic bariatric interventions Endoscopic procedures slowed gastric emptying, improving satiety Surgical & endoscopic Meta-analysis Gastric emptying half-time, weight loss
4 Rapaka et al.[15] Examine physiological appetite changes post-ESG & intragastric balloon (IGB) Both ESG and IGB suppressed ghrelin, reduced hunger signals Endoscopic 72 Ghrelin levels, satiety scores
5 Bickerdike et al.[3] Explore 5-HT2C receptor agonists for obesity 5-HT2C receptor modulation reduces appetite & promotes weight loss Pharmacological Preclinical studies Appetite suppressio, weight loss trends
6 Liu et al.[16] Investigate selective 5-HT2C agonists for obesity treatment Novel proline amides show high receptor selectivity for weight loss Pharmacological Preclinical Receptor activity, weight change
7 Martin et al.[17] Study lorcaserin (5-HT2C agonist) on appetite & weight Lorcaserin reduced energy intake without affecting expenditure Pharmacological 150 Energy intake, body weight
8 Wilding et al.[7] Investigate semaglutide (GLP-1 agonist) for weight loss 14.9% body weight reduction in 68 weeks Pharmacological 1,961 Weight loss, glycated hemoglobin (HbA1c), lipid profile
9 Rubino et al.[18] Evaluate metabolic surgery vs. medical therapy in diabetes management Bariatric surgery led to better glycemic control vs. medication alone Surgical 150 HbA1c, insulin sensitivity, weight
10 Garvey et al.[19] Compare tirzepatide vs. semaglutide in obesity Tirzepatide showed superior weight loss vs. semaglutide (20% vs. 14%) Pharmacological 2,539 Weight reduction, metabolic markers
11 Wadden TA  et al.[20] Assess effectiveness of naltrexone-bupropion in obesity Combination therapy reduced body weight by 8% at 56 weeks Pharmacological 4,500 Weight loss, BMI change
12 Salminen et al.[21] Compare long-term outcomes of sleeve gastrectomy vs. gastric bypass Gastric bypass had slightly greater long-term weight loss Surgical 240 % excess weight loss, comorbidity resolution
13 Hall et al.[22] Examine diet-induced vs. surgery-induced metabolic changes Surgery led to more sustained metabolic improvements than diet alone Dietary & surgical 400 Metabolic markers, weight maintenance
14 Verrastro O et al.[23] Evaluate gut microbiome changes post-bariatric surgery Significant shifts in microbiome composition linked to improved metabolism Microbiome-focused 150 Gut microbiota diversity, metabolic parameters
15 Wharton et al.[24] Systematic review on pharmacotherapy post-bariatric surgery Pharmacotherapy may aid weight loss post-surgery; more rigorous research needed Pharmacological 13 studies reviewed Weight loss, safety profile
16 Cohen et al.[25] Systematic review on obesity-management medications pre- and post-bariatric surgery Medications can be beneficial adjuncts; further studies required Pharmacological Multiple studies reviewed Weight loss, metabolic outcomes
17 Saudi Medical Journal[26] Clinical practice guidelines for obesity management in adults Recommends metformin and orlistat as pharmacological options Pharmacological Guideline Weight loss, safety considerations
18 Robinson et al.[9] The psychology of obesity Evidence-based map Psychology Multiple studies Psychological correlates of heavier body weight
19 Pop et al.[27]  literature review of advancements in obesity and diabetes Diabetes is best managed in multidisciplinary units Clinicals Multiple studies Diabetes management
20 Di Vincenzo et al.[28] Physics and innovations Bioelectrical impedance (BIA) is key in management

 

  Clinicals

 

 Systematic review Weight loss
21 Aleksandrova et al[29] Biomarkers in obesity Novel etiological insights and targets for precision prevention Narrative Guidelines Weight loss, safety considerations
22 Okorodudu  et al.[10] Innovative interventions Behavioral change in overweight or obese individuals Psychologyical Literature review Psychological correlates of heavier body weight
23 Gilmore et al.[30] Technological Trends Evidence-based map Clinicals Case reviews Weight loss management
24 Tran et al.[31] Obesity Treatments  Overview of GLP 1 Agonists Pharmacological Clinical trials Weight loss
25 Chen et al.[11] Morbid Obesity Treatments GLP 1 Agonists & Surgery Multidisciplinary Case reviews Weight loss
26 Perrotta et al.[1] Innovative interventions Novel surgical interventions Surgical Narrative reviews Weight loss, safety considerations

Table 2: Data charting of relevant studies

Line graph showing the effectiveness of pharmacotherapies

Figure 2: Line graph showing the effectiveness of pharmacotherapies, particularly GLP-1 receptor agonists, in promoting weight loss and metabolic health

The graph compares weight loss percentages achieved with GLP-1 receptor agonists against placebo or other treatments over time. The data suggest that GLP-1 receptor agonists lead to significantly greater and more sustained weight loss compared to alternatives, reinforcing their role as effective pharmacotherapies for obesity and metabolic disorders.

Forest plot showing the effectiveness of pharmacotherapies

Figure 3: Forest plot showing the effectiveness of pharmacotherapies, particularly GLP-1 receptor agonists, in promoting weight loss and metabolic health

The forest plot represents the weight loss effects of GLP-1 receptor agonists compared to placebo and other treatments. The blue dots indicate the mean percentage weight loss, with horizontal lines representing 95% confidence intervals (CI 95%). This visualization highlights the significantly greater weight loss associated with GLP-1 receptor agonists (>14%) compared to placebo and other treatments (<4%).

Line graph comparing the clinical outcomes of minimally invasive and traditional bariatric procedures

Figure 4: Line graph comparing the clinical outcomes of minimally invasive and traditional bariatric procedures, showcasing the complication rate and length of hospital stay

The blue line represents complication rates, and the green line shows the length of stay. Minimally invasive bariatric procedures, such as laparoscopic and endoscopic techniques, have been shown to offer advantages over traditional open surgeries in terms of complication rates and hospital length of stay. These findings suggest that minimally invasive approaches can lead to reduced complication rates (<5%) and shorter hospital stays (<2 days) compared to traditional bariatric surgeries.

Line graph to illustrate the impact of genetic predisposition, gut microbiota alterations

Figure 5: Line graph to illustrate the impact of genetic predisposition, gut microbiota alterations, and epigenetic factors on obesity and evaluate their potential as therapeutic targets

The graph highlights that epigenetic factors and genetic predisposition have a slightly higher impact (>80%) than gut microbiota alterations. However, all three factors play a significant role in obesity development. Understanding these influences can help in designing targeted therapeutic strategies, such as personalized medicine, microbiome interventions, and epigenetic modifications, to manage and prevent obesity.

Bar chart comparing the mean improvements in weight loss, glycemic control, and safety outcomes

Figure 6: Bar chart comparing the mean improvements in weight loss, glycemic control, and safety outcomes between pharmacological and surgical intervention (MI = Mean improvements)

While bariatric surgery tends to offer more substantial improvements (MI >50%) in weight loss and glycemic control, it involves higher upfront risks and costs. Pharmacological interventions provide more moderate benefits with a different side effect profile. NB: The choice between these approaches should be individualized, considering patient-specific factors and preferences.

Discussion

In conducting this systematic review on the chemobiology of obesity and recent advances in the field, a rigorous screening process was employed to ensure the inclusion of high-quality and relevant studies. The initial broad search across electronic databases yielded a total of 12,678 research records. Following the removal of 5,443 duplicate entries, 7,235 unique records were retained.

To refine the selection, MeSH terms were applied, resulting in the exclusion of 7,083 records that did not meet the predefined criteria, leaving 152 studies for further evaluation. The first stage of screening, which involved reviewing titles and abstracts, led to the retention of 152 records. Of these, 98 articles were excluded based on study criteria, resulting in 54 full-text articles for the second stage of screening.

During the final screening stage, 28 articles were removed due to redundant outcome measures, leaving a total of 26 high-quality studies included in the systematic review. This multi-step selection process ensured that only the most relevant and scientifically rigorous studies contributed to the final synthesis, thereby strengthening the reliability of the findings in understanding the complex interplay between chemobiological factors and obesity.

This systematic review delved into the chemobiological mechanisms underlying obesity and evaluated innovative therapeutic approaches, including pharmacological advancements and bariatric interventions. The findings underscore the multifaceted nature of obesity, encompassing biochemical, molecular, and environmental factors.

Obesity is characterized by complex interactions between genetic predisposition, hormonal imbalances, and environmental influences. Recent studies have highlighted the role of environmental chemicals, termed “obesogens,” in disrupting metabolic processes. These chemicals can alter lipid metabolism and energy homeostasis, contributing to weight gain and insulin resistance. A review by Martin et al.[17] emphasized that the HT2C receptor agonist reduces body weight by decreasing energy intake without influencing energy expenditure, suggesting a superior treatment in this regard.

Furthermore, oxidative stress has been implicated in the pathophysiology of obesity. Elevated oxidative stress can lead to mitochondrial dysfunction and inflammation, exacerbating metabolic disturbances. There are further discussions on how oxidative stress interacts with hormonal pathways, influencing appetite regulation, psyche, and energy expenditure, thereby promoting fat accumulation.[9,14]

Advancements in pharmacotherapy have introduced novel agents targeting specific metabolic pathways. GLP-1 receptor agonists, such as semaglutide, have demonstrated significant efficacy in promoting weight loss and improving metabolic health.[11] These agents enhance insulin secretion, suppress appetite, and slow gastric emptying, leading to reduced caloric intake. Recent clinical trials have reported substantial weight reduction with semaglutide use, highlighting its potential as a cornerstone in obesity management.[11]

Additionally, the exploration of adipocyte-targeted therapies, including nanotechnology and cell-based approaches, offers promising avenues. There is also the potential of nanotechnology and cell-based therapies, particularly adipose-derived mesenchymal stem cells, in targeting adipocytes to regulate lipid metabolism and treat obesity.[16] Bariatric procedures have evolved from traditional surgical methods to minimally invasive techniques aimed at reducing complications and enhancing patient recovery. Innovations such as endoscopic sleeve gastroplasty and intragastric balloon placement have shown efficacy in inducing weight loss with favorable safety profiles. Comparative studies indicate that while these procedures may offer less weight reduction than traditional surgeries, they present viable options for patients seeking less invasive solutions.

The interplay between environmental exposures and genetic factors is crucial in understanding individual susceptibility to obesity.[15,30] Also, exposure to environmental contaminants can impede weight loss and glycemic control during calorie-restricted diets, suggesting that environmental factors may influence the effectiveness of obesity interventions.[12] There are notable variations in genes related to fat taste and smell perception, which may affect fat consumption and contribute to obesity risk. Genetic predispositions, including polymorphisms affecting taste and smell receptors, can influence dietary preferences and energy balance.[1,9]

This review underscores the complexity of obesity, driven by a confluence of chemobiological mechanisms, environmental exposures, and genetic factors. Innovative pharmacological and bariatric interventions offer promising avenues for treatment, yet personalized approaches considering individual environmental and genetic contexts are essential. Future research should continue to elucidate these intricate interactions to develop targeted and effective obesity therapies.

Study limitations: Although the researchers encountered several study limitations, it was maintained at the barest minimum through effective data collection and synthesis techniques. In particular, the researchers noticed that there was a potential for language selection bias due to the stringent, but necessary, inclusion and exclusion criteria applied during the literature search. While efforts were made to capture a comprehensive range of studies, some relevant articles may have been inadvertently omitted, particularly those published in non-indexed journals or in languages other than English.

Although the systematic review employed high-quality studies through the PRISMA flowchart, there could be a risk of inherent publication bias, which must be considered, regardless. Only published studies were identified and screened, as there was no practical access to the unpublished ones. In addition to this, variability in study quality and methodologies presented quite a challenge. The included studies exhibited heterogeneity in terms of study design, sample size, intervention types, and outcome measures. Although this could have the potential to limit direct comparability, this was effectively minimized through the application of a multi-dimensional systematic review process, retaining multidisciplinary studies. Furthermore, studies that relied exclusively on observational data were screened out due to their inherent risks of confounding and bias.

Finally, despite advances in chemobiology and bariatrics, certain aspects remain underexplored. The long-term effects of newer bariatric interventions, particularly at the molecular and metabolic levels, would require further investigation, hence the need for more research. While this review highlights promising fields, the translation of these findings into clinical practice necessitates further studies to address these gaps and refine our understanding of obesity.

Conclusion

Obesity remains a multifaceted condition with profound implications for public health, necessitating an integrative approach that spans molecular biology, clinical interventions, and technological advancements. This systematic review highlights the evolving understanding of the chemobiology of obesity, including the intricate interplay between metabolic pathways, gut microbiota, adipose tissue dynamics, and inflammatory processes. The insights gained from this field have significantly influenced the development of novel pharmacological agents, precision medicine approaches, and innovative bariatric techniques aimed at improving long-term weight management and metabolic outcomes.

Advancements in bariatric medicine, including minimally invasive surgical procedures, endoscopic therapies, and pharmacotherapeutic agents targeting neuroendocrine pathways, have redefined obesity management beyond conventional lifestyle interventions. However, despite these promising developments, challenges remain, particularly regarding long-term efficacy, sustainability, and the integration of personalized treatment strategies. Future research should focus on bridging the gap between basic scientific discoveries and clinical applications, optimizing patient outcomes while minimizing risks.

Ultimately, the interplay between chemobiological mechanisms and bariatric innovations offers a compelling avenue for reshaping obesity treatment paradigms. A multidisciplinary, patient-centered approach that incorporates emerging research, technological progress, and individualized treatment algorithms will be crucial in addressing the growing global burden of obesity.

References

  1. Perrotta G, Bocchinfuso S, Jawhar N, et al. Novel surgical interventions for the treatment of obesity. J Clin Med. 2024;13(17):5279. doi:10.3390/jcm13175279 PubMed | Crossref | Google Scholar
  2. World Health Organization. Prevalence of obesity among adults (BMI ≥ 30) (age-standardized estimate). World Health Organization. Prevalence of obesity among adults, BMI >= 30 (age-standardized estimate) (%)
  3. Bickerdike MJ, Vickers SP, Dourish CT. 5‐HT2C receptor modulation and the treatment of obesity. Diabetes Obes Metab. 1999;1(4):207-214. doi:10.1046/j.1463-1326.1999.00037.x PubMed | Crossref | Google Scholar
  4. Garfield AS, Heisler LK. Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol. 2009;587(1):49-60. doi:10.1113/jphysiol.2008.164152 PubMed | Crossref | Google Scholar
  5. Friedman JM. Leptin and the endocrine control of energy balance. Nat Metab. 2019;1(8):754-764. doi:10.1038/s42255-019-0095-y PubMed | Crossref | Google Scholar
  6. Wong HJ, Sim B, Teo YH, et al. Efficacy of GLP-1 Receptor Agonists on Weight Loss, BMI, and Waist Circumference for Patients With Obesity or Overweight: A Systematic Review, Meta-analysis, and Meta-regression of 47 Randomized Controlled Trials. Diabetes Care. 2025;48(2):292-300. doi:10.2337/dc24-1678 PubMed | Crossref | Google Scholar
  7. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183 PubMed | Crossref | Google Scholar
  8. Myers MG Jr, Heymsfield SB, Haft C, et al. Challenges and opportunities of defining clinical leptin resistance. Cell Metab. 2012;15(2):150-156. doi:10.1016/j.cmet.2012.01.002 PubMed | Crossref | Google Scholar
  9. Robinson E, Roberts C, Vainik U, Jones A. The psychology of obesity: An umbrella review and evidence-based map of the psychological correlates of heavier body weight. Neurosci Biobehav Rev. 2020;119:468-480. doi:10.1016/j.neubiorev.2020.10.009 PubMed | Crossref | Google Scholar
  10. Okorodudu DE, Bosworth HB, Corsino L. Innovative interventions to promote behavioral change in overweight or obese individuals: A review of the literature. Ann Med. 2015;47(3):179-185. doi:10.3109/07853890.2014.931102
    PubMed | Crossref | Google Scholar
  11. Chen JH, Tang WH, Lee CH. Effective weight loss after treatment with a glucagon-like peptide-1 receptor agonist in a morbidly obese and diabetic patient before bariatric surgery: a case report. J Med Case Rep. 2014;8:304. doi:10.1186/1752-1947-8-304 PubMed | Crossref | Google Scholar
  12. Lopez-Nava G, Sharaiha RZ, Vargas EJ, et al. Endoscopic Sleeve Gastroplasty for Obesity: a Multicenter Study of 248 Patients with 24 Months Follow-Up. Obes Surg. 2017;27(10):2649-2655. doi:10.1007/s11695-017-2693-7
    PubMed | Crossref | Google Scholar
  13. Abu Dayyeh BK, Acosta A, Camilleri M, et al. Endoscopic Sleeve Gastroplasty Alters Gastric Physiology and Induces Loss of Body Weight in Obese Individuals. Clin Gastroenterol Hepatol. 2017;15(1):37-43.e1. doi:10.1016/j.cgh.2015.12.030 PubMed | Crossref | Google Scholar
  14. Vargas EJ, Bazerbachi F, Calderon G, et al. Changes in time of gastric emptying after surgical and endoscopic bariatrics and weight loss: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2020;18(1):57-68.e5. doi:10.1016/j.cgh.2019.03.047 PubMed | Crossref | Google Scholar
  15. Rapaka B, Maselli DB, Lopez-Nava G, et al. Effects on physiologic measures of appetite from intragastric balloon and endoscopic sleeve gastroplasty: results of a prospective study. Chin Med J (Engl). 2022;135(10):1234-1241. doi:10.1097/CM9.0000000000002097 PubMed | Crossref | Google Scholar
  16. Liu KKC, Lefker BA, Dombroski MA, et al. Orally active and brain permeable proline amides as highly selective 5HT2c agonists for the treatment of obesity. Bioorg Med Chem Lett. 2010;20(7):2365-2369. doi:10.1016/j.bmcl.2010.01.107 Crossref | Google Scholar
  17. Martin CK, Redman LM, Zhang J, et al. Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J Clin Endocrinol Metab. 2011;96(3):837-845. doi:10.1210/jc.2010-1848 PubMed | Crossref | Google Scholar
  18. Rubino F, Nathan DM, Eckel RH, et al. Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations. Diabetes Care. 2016;39(6):861-877. doi:10.2337/dc16-0236 PubMed | Crossref | Google Scholar
  19. Garvey WT. Is Obesity or Adiposity-Based Chronic Disease Curable: The Set Point Theory, the Environment, and Second-Generation Medications. Endocr Pract. 2022;28(2):214-222. doi:10.1016/j.eprac.2021.11.082
    PubMed | Crossref | Google Scholar
  20. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: The COR‐BMOD trial. Obesity (Silver Spring). 2011;19(1):110-120. doi:10.1038/oby.2010.147
    PubMed | Crossref | Google Scholar
  21. Salminen P, Helmiö M, Ovaska J, et al. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial. 2018;319(3):241-254. doi:10.1001/jama.2017.20313 PubMed | Crossref | Google Scholar
  22. Hall KD, Ayuketah A, Brychta R, et al. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metab. 2019;30(1):67-77.e3. doi:10.1016/j.cmet.2019.05.008 PubMed | Crossref | Google Scholar
  23. Verrastro O, Panunzi S, Castagneto-Gissey L, et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial. 2023;401(10390):1786-1797. doi:10.1016/s0140-6736(23)00634-7 PubMed | Crossref | Google Scholar
  24. Wharton S, Liu A, Pakseresht A, et al. Real-World Clinical Effectiveness of Liraglutide 3.0 mg for Weight Management in Canada. Obesity (Silver Spring). 2019;27(6):917-924. doi:10.1002/oby.22462 PubMed | Crossref | Google Scholar
  25. Cohen RV, Park JY, Prager G, et al. Role of obesity-management medications before and after metabolic bariatric surgery: a systematic review. Br J Surg. 2024;111(12):znae284. doi:10.1093/bjs/znae284
    PubMed | Crossref | Google Scholar
  26. Alfadda AA, Al-Dhwayan MM, Alharbi AA, et al. The Saudi clinical practice guideline for the management of overweight and obesity in adults. Saudi Med J. 2016;37(10):1151-1162. doi:10.15537/smj.2016.10.14353
    PubMed | Crossref | Google Scholar
  27. Pop GN, Manole F, Buleu F, et al. Bridging the gap: A literature review of advancements in obesity and diabetes mellitus management. Appl Sci (Basel). 2024;14(15):6565. doi:10.3390/app14156565 Crossref | Google Scholar
  28. Marra M, Di Vincenzo O, Sammarco R, Morlino D, Scalfi L. Bioimpedance phase angle in elite male athletes: a segmental approach. Physiol Meas. 2020;41(12):125007. doi:10.1088/1361-6579/abcb5c
    PubMed | Crossref | Google Scholar
  29. Aleksandrova K, Egea Rodrigues C, Floegel A, Ahrens W. Omics Biomarkers in Obesity: Novel Etiological Insights and Targets for Precision Prevention. Curr Obes Rep. 2020;9(3):219-230. doi:10.1007/s13679-020-00393-y
    PubMed | Crossref | Google Scholar
  30. Gilmore LA, Duhé AF, Frost EA, Redman LM. The technology boom: a new era in obesity management. J Diabetes Sci Technol. 2014;8(3):596-608. doi:10.1177/1932296814525189 PubMed | Crossref | Google Scholar
  31. Tran KL, Park YI, Pandya S, et al. Overview of Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Patients with Type 2 Diabetes. Am Health Drug Benefits. 2017;10(4):178-188. Overview of Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Patients with Type 2 Diabetes – PMC PubMed | Google Scholar

Acknowledgments

Data were sourced and referenced in line with ethical standards of the General Data Protection Regulation (GDPR). We thank the World Obesity Federation Global Obesity Observatory for access to quality, relevant study materials.

Funding

Not reported

Author Information

Corresponding Author:
Chinua Onyebuchi
Department of Public Health
Liverpool John Moores University, UK
Email: chinuaonyebuchi@gmail.com

Co-Authors:
Adesewa Adebiyi Rachael
Department of Public Health
Western Illinois University, USA

Kelvin Aizebhughele
Department of Public Health
Health Science and Safety Institute, UK

Chijioke Eze, Chuba Samuel Jeremiah, Oluchi Hope Uzochukwu Obi
Department of Medicine
Nnamdi Azikiwe University Teaching Hospital, Nigeria

David Izuchukwu Onyebuch, Alswell Okechukwu Onyebuchi
Department of Medicine
V. N. Karazin Kharkiv National University, Kharkiv, Ukraine

Authors Contributions

Chinua Onyebuchi was responsible for the introduction, conceptualization, data collection, analysis, data charting, abstract, discussion, proofreading, and funding. Adesewa Adebiyi Rachael contributed to data collection, epidemiology, subgroup analysis, charting, and funding. Kelvin Aizebhughele handled data collection, case discussion, analysis, subgroup data charting, and funding. Chijioke Eze was involved in data collection, case discussion, analysis, table creation, and funding. David Izuchukwu Onyebuchi contributed to data analysis, discussion, and funding. Chuba Samuel Jeremiah handled referencing checks, methods, conclusion, and funding. Oluchi Hope Uzochukwu Obi worked on the systematic review, analysis, data tables, and funding. Alswell Okechukwu Onyebuchi was responsible for referencing checks, systematic review, conclusion, and funding.

Ethical Approval

Not applicable

Conflict of Interest Statement

The authors declare no conflicts of interest.

Guarantor

None

DOI

https://doi.org/10.63096/medtigo30623130

Cite this Article

Chinua O, Adesewa AR, Kelvin A, et al. Chemobiology of Obesity and Advances in Bariatrics: A Systematic Review. medtigo J Med. 2025;3(1):e30623130. doi:10.63096/medtigo30623130 Crossref

ALTMETRICS

Citations 2

Cite This