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OBESITY RELATIONSHIP, METABOLIC SYNDROME AND INSULIN
RESISTANCE: A SYSTEMATIC REVIEW
João Vitor Cavalcante Alves1
Abstract: Objective: The present study aims to describe the relationship of obesity with metabolic
syndrome and insulin resistance in obese patients. Methodology: The present study is a bibliographic
review that seeks to study articles on the biochemistry of obesity and insulin resistance. 18,955
PUBMED databases and Virtual Health Library of the Ministry of Health were consulted with the
following lters: randomized study articles and epidemiological review articles. Articles written in
English published between 2006 and 2023 were used in the research. The research was conducted
in 2 phases: articles and summaries screening phase that were used in the bibliographic review
where 7 articles were selected, then the work were read and built the Scientic article. RESULTS:
Longitudinal research of literature review points out that obesity develops an inammatory process
of dysfunctional adipocytes where cytokines ampha and macrophages are triggered causing
an accumulation of systemic fatty acids in the body’s tissues such as: liver and muscle pancreas
generating lipotoxicity and one one Systemic inammation that prevents adequate insulin signaling.
Metabolic syndrome was diagnosed in 45.5% of obese patients and insulin resistance at 29.1%. Insulin
resistance had an association with HDL-cholesterol (p = 0.032) and with metabolic syndrome (p
= 0.006). The body composition indicators were correlated with insulin resistance (p <0.01). The
values of 23.5 and 36.3% above the IMC reference point allowed to identify insulin resistance
and metabolic syndrome in patients. Conclusion: The present study sought to review the literature
on the relationship of obesity, biochemistry and insulin resistance. Studies indicate that 45.5% of
obsessed patients have metabolic diseases arising from obesity such as insulin resistance, tissue
lipotoxicity and diabetes, which occur due to the inammatory process of anf-alpha cytokines in
1 Medical student from the University Center of João Pessoa - Unipe
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adipose tissue dysfunctional obese patients leading to a signicant loss of the patient’s quality of life.
Keywords: insulin resistance; interference between organs; muscular atrophy; obesity.
Introduction
Obesity is a clinical condition whose prevalence has grown alarmingly in recent decades.
From 1975 to 2014, the number of obesity cases tripled, and by 2022, it is estimated that about 1
billion individuals around the world were obese. Obesity is now widely recognized as a global
pandemic, aecting adults, children and adolescents in various sociocultural and economic contexts.
Its classication as a pandemic stems not only from its universal reach, but also from the serious
consequences that entails for public health. Obesity is strongly associated with a number of adverse
conditions, including cardiovascular disease, metabolic diseases and a signicant increase in the
risk of various cancers. Additionally, this condition is linked to a considerable reduction in life
expectancy, underlining the urgent need for eective interventions. Among the metabolic conditions
most commonly associated with obesity are insulin resistance and type 2 diabetes indicate that
approximately 29.1% of obese patients develop these metabolic changes, which highlights the
complexity and severity of the impact of obesity on health metabolic. Insulin resistance, a pathological
state where body cells do not respond adequately to the hormone insulin, is a direct consequence of
obesity and is often present in individuals with metabolic syndrome. This syndrome is characterized
by a set of conditions, including arterial hypertension, dyslipidemia and hyperglycemia, which
together increase the risk of development of cardiovascular disease and type 2 diabetes. The
relationship between obesity, insulin resistance and metabolic syndrome is intrinsically linked,
creating one Metabolic deterioration cycle that compromises the health of the individual. This study
reviews the existing literature to analyze the interrelationship between obesity, insulin resistance
and metabolic syndrome, highlighting underlying pathophysiology and the mechanisms involved.
Understanding these mechanisms is crucial to identifying eective interventions and preventive
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strategies that can improve patients’ quality of life and reduce associated mortality. The importance of
this study lies in the need to face the global crisis of obesity and its metabolic complications, providing
insights for the implementation of public health policies and more eective clinical treatments.
Objective
The present study aims to describe the relationship of obesity with metabolic syndrome and
insulin resistance in obese patients.
Methodology
The present study consists of a comprehensive bibliographic review, with the objective
of investigating and analyzing the relationship between obesity, metabolic syndrome and insulin
resistance through biochemistry underlying these conditions. To ensure a strict and comprehensive
approach, a detailed search was conducted in the available scientic literature. Initially, two main
databases were consulted: PubMed and the Ministry of Health’s Virtual Health Library (BVS). These
databases were selected due to their wide coverage and relevance in health. The search was performed
using specic lters to rene the results and focus on studies with greater methodological robustness.
The lters applied included the selection of articles from randomized studies and epidemiological
reviews, ensuring that only the most relevant and reliable literature was considered. The survey
covered articles published between 2006 and 2023, ensuring the inclusion of recent and relevant data
for the current context. The descriptors used in the search were “insulin”, “resistance”, “obesity”
and “diabetes”. These terms were chosen to reect the main aspects of the theme under study and
facilitate the identication of articles that directly address biochemistry and interactions between
obesity, insulin resistance and diabetes. The review process was divided into two main phases. In the
rst phase, the initial screening of the articles and summaries was performed. At this stage, a total of
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18,955 articles were evaluated to select those who aligned with the established inclusion criteria. The
screening was made based on the relevance of the title, summary and, when necessary, of the full
text of the articles. After screening, 7 articles were selected that met the inclusion criteria and which
had an in -depth analysis of the topics of interest. In the second phase, the selected articles were read
in full and critically analyzed to extract relevant and relevant information about the biochemistry of
obesity and insulin resistance.
Results
P Russell (2004) suggests that accumulation of intramiellular triglycerides (IMTG) may
play a signicant role in the development of insulin resistance, particularly in obese and diabetic
patients. It has been observed that high levels of IMTGs are correlated with insulin resistance in
these individuals, which is not the case in resistance trained individuals (ETR). This dierence can
be attributed, in part, to variations in gene expression and key enzyme activities involved in the
transport and oxidation of fatty acids, as well as the state of peroxidation of IMTGs between obese/
diabetic patients and individuals ETR. The research points out that the homeostasis of fats and lipids
in the skeletal muscles can be interrupted by activation of kinase c (PKC) protein, which positively
interferes with various signaling pathways, including those mediated by insulin and IKK/NFKB. In
addition, increased peroxidation of IMTGs can reduce insulin sensitivity, raising tnf-alpha levels, a
proinammatory cytokine that increases the expression of cytokine signaling suppressor proteins
(PCS). Both PKC activation and increase in TNF-alpha and SOCS3 levels result in the inhibition
of IRS-1 tyrosine phosphorylation, a crucial step in insulin signaling road, which compromises its
activation and, consequently, downstream signaling.
C Lelliott (2004) addresses obesity and type 2 diabetes mellitus as the main public health
problems of the 21st century, highlighting the importance of developing eective strategies to prevent
and treat obesity. However, despite scientic advances in identifying weight regulatory pathways, the
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obesity epidemic continues to expand faster than scientic progress, especially in a aging population.
This can lead to an subsequent uncontrolled epidemic of complications associated with obesity.
The main focus of the research lies in the mechanisms that cause lipotoxicity, in order to identify
appropriate strategies to prevent or slow the development of metabolic syndrome. Previous studies
using transgenic mice and knockout models have revealed a signicant interaction between white
adipose tissue and skeletal muscle, where fatty acid synthesis (FA) on adipose tissue has reciprocal
eects on FA oxidation on skeletal muscle. Research suggests that adipose tissue dysfunction is a
crucial link between obesity, insulin resistance and type 2 diabetes, as it promotes the development
of lipotoxicity in peripheral tissues. In an energy -rich environment, adipose tissue reacts in ways
that depend on genetic and physiological factors, impacting the functions of other peripheral tissues.
The models proposed in research describe how adipose tissue can respond to an excessive energy
environment, inuencing the energy balance between dierent organs.
Thomas Plötz (2024) explores the harmful eects of free fatty acids (FFAS) on various
cell functions on pancreatic beta cells, which are essential for insulin production and regulation.
Traditionally, studies in this area have focused on the eects of more common physiological fatty
acids such as palmitic acid and oleic acid. However, this limited approach does not consider variations
in FFAS structure, such as chain length and saturation degree, which can signicantly inuence
lipotoxicity mechanisms. For a broader understanding of lipotoxicity mechanisms, research suggests
that it is necessary to investigate a wide range of structurally related FFAS. Studies using Endoc-
βH1 Human Beta Beta Line have allowed detailed analysis of FFAS structural-activity relationships,
providing deep insights on how dierent FFAs contribute to beta cell lipotoxicity. Research points
out that certain structural characteristics of FFAS play a crucial role in Development of lipotoxicity
in human beta cells. These ndings are particularly relevant in the context of obesity and type 2
diabetes, where there is an increase in triglyceride reserves. This accumulation of triglycerides is
associated with greater lipotoxicity, which can compromise the function of beta cells and contribute
to the progression of diabetes.
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Ruth C R Meex (2019) explores the relationship between insulin resistance, muscle loss and
type 2 diabetes, highlighting how these factors often coincide, especially in overweight patients.
Obesity and disorders in lipid metabolism play crucial roles in the development of insulin resistance,
particularly due to the increase in the mass of adipose tissue and the dysfunction of this tissue, which
result in a systemic overow of lipids and low -grade inammation, mediated by secretion altered
adipocins and cytokines. The study points out that the increased ow of fatty acids from adipose tissue
contributes to increased fat storage in the liver and skeletal muscle. This can lead to altered secretion
of hepatocinas, mitochondrial dysfunction and insulin signaling compromised in skeletal muscle.
These processes not only exacerbate insulin resistance, but are also associated with the development
of muscle atrophy, suggesting that insulin resistance and muscle loss can be two sides of the same
coin. Although the exact connection between lipid accumulation, type 2 diabetes and muscle atrophy
is still largely unexplored, research suggests that lipid disorders in peripheral tissues such as liver and
skeletal muscle play an important role. These disorders may aect peripheral sensitivity to insulin and
muscle mass through common pathways such as mitochondrial dysfunction and cytokine -mediated
inammation.
G Las (2010) investigates the role of autophagy, a cellular catabolic process, in the health of
pancreatic beta cells and their implication in diabetes. Autophagia, involved in both cellular survival
and cell death, is crucial for adequate insulin secretion and the viability of beta cells. In experimental
models, such as transgenic mice that do not have beta cell autophagia, a decrease in these cells and a
reduction in insulin secretion in response to glucose was observed. Several studies indicate that stress
can stimulate autophagia in beta cells. The increase in the number of autofagosomes was observed
in several in vivo models of diabetes, such as mice DB/DB, mice fed with rich fat diet, PDX-1
Knockout mice, as well as in vitro models of glucotoxicity and lipotoxicity. The pharmacological and
molecular inhibition of autophagia has shown to increase susceptibility to cell stress, suggesting that
autophagia can play a protective role against diabetes relevant stresses. However, recent discoveries
release doubts about these conclusions. In diabetic pancreas and beta cells exposed to fatty acids,
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it was observed the accumulation of abnormal morphology autofagosomes and the suppression of
expression of lysomal genes, suggesting a compromise in the self -lled turnover. This indicates that
under certain conditions, autophagia may be impaired, contributing to cell dysfunction rather than
protecting against stress.
Takashi Kadowaki (2022) Research on cardio-renal metabolic disease (CRM) explores the
complex interaction between metabolic disorders, cardiovascular disease (CVD) and renal dysfunction,
highlighting the interconnection between these conditions and their implications for global health.
CRM is dened as multidirectional interaction between metabolic diseases such as type 2 diabetes
(T2D), various types of cardiovascular diseases, and chronic kidney disease (CKD). Type 2 diabetes
increases the risk of heart failure, a well -known aspect that has only recently received more attention
in treatment. In addition, there are variations in the risk of heart failure based on ethnicity, and
atherosclerotic heart disease is a well -established T2D complication. Many patients with T2D also
develop CKD, with a particularly high risk among Asians compared to their western counterparts.
The research also points out that CVD increases the risk of CKD and vice versa, with heart failure
present in approximately half of patients with CKD. Molecular mechanisms involved in CRM diseases
include hyperglycemia, insulin resistance, renin-angiotensin-aldosterone hyperactivity, advanced
glycation product production, oxidative stress, lipotoxicity, endoplasmic reticulum stress, calcium
handling abnormalities, mitochondrial dysfunction, poor energy production and chronic inammation.
Pathophysiological manifestations of these processes include diabetic cardiomyopathy, vascular
endothelial dysfunction, cardiac and renal brosis, glomerular hyperlling, renal hypoperfusion,
venous congestion, tolerance reduction to metabolic dysfunction, and calcication of atherosclerotic
plaques.
Conclusion
The present study sought to review the literature on the relationship of obesity, biochemistry
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and insulin resistance. Studies indicate that 45.5% of obese patients have had metabolic diseases
arising from obesity, such as insulin resistance, tissue lipotoxicity and diabetes. These conditions are
attributed to the proinammatory process of TNF-Alpha cytokines in obese patients’ dysfunctional
fat, which results in a signicant loss of quality of life. As with respiratory complications that can be
divided into bass and light, the metabolic consequences of obesity also vary in gravity. Laryngospasm,
for example, is a severe complication, while the persistent stricker and cough are considered less severe
but still important. Similarly, insulin resistance and lipotoxicity can be seen as severe manifestations
of obesity, while other metabolic complications may have a less immediate but equally impactful
presentation. Eective prevention and management of these metabolic complications follow a similar
approach to respiratory complications: require early identication and adequate intervention. In the
case of obesity and insulin resistance, prophylactic strategies include the implementation of lifestyle
changes such as diet and exercise, and, when necessary, directed pharmacological interventions.
Just as the use of simulators and training is eective in diculty management, education and
continuous training on health practices and obesity control are crucial to improving results and
reducing the impact of metabolic diseases. Therefore, recognizing and treating obesity and its
complications associated holistically and early is fundamental to prevent disease progression and
improve patients’ quality of life. Proper management with integrated interventions can lead to
signicant improvement in metabolic health and reduce the adverse eects associated with obesity.
References
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