Synbiotics in Metabolic Disorders Mechanisms, Therapeutic
Potential, and Future Perspectives 1st Edition
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Synbiotics in Metabolic Disorders
Mechanisms, Therapeutic Potential,
and Future Perspectives
Edited by
Neeraj Mishra, Sumel Ashique, Arshad Farid,
and Ashish Garg
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First edition published 2025
by CRC Press
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ISBN: 9781032702414 (hbk)
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DOI: 10.1201/9781032702438
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Contents
List of Contributors...............................................................................................................................................................vii
About the Editors...................................................................................................................................................................xi
Chapter 1 An Introduction on Metabolic Disorders..........................................................................................................1
Yash Jasoria, Mohit Agrawal, and Hema Chaudhary
Chapter 2 Targeting Signaling Pathway and Mechanism of Prebiotics, Probiotics, and Synbiotics
to Manage Metabolic Disorders...................................................................................................................... 10
Monika Kaushik, Prathap Madeswaraguptha, Murugesan Vanangamudi,
Vijayaraj Surendran, Navaneetha Krishnan Subramaniyan, and Ashok Kumar
Chapter 3 Potential Role of Probiotics, Prebiotics, and Synbiotics in Management of Metabolic
Syndrome and Chronic Metabolic Disease..................................................................................................... 39
Md. Khokon Miah Akanda and Sanzia Mehjabin
Chapter 4 Synbiotics and Gut Microflora: Mechanisms and Therapeutic Rationality
and Clinical Applications for Management of Type 2 Diabetes..................................................................... 55
Nisha Sharma, Prakash Chandra Gupta, Swarnakshi Upadhyay, and Kamla Pathak
Chapter 5 Exploring Gut Microbiota as Therapeutic Target to Maintain Metabolic Health........................................... 68
Anas Islam, Aditya Singh, Asad Ahmad, Badruddeen, Juber Akhtar, Usama Ahmad,
Mohammad Irfan Khan, Mohammad Ahmad, and Yusuf Asad
Chapter 6 The Impact of Probiotic and Synbiotic Supplementation on Oxidative Stress
and Inflammation............................................................................................................................................90
Himanshu Sharma, Sanjesh Kumar, Sumel Ashique, Pratibha Bhowmick, Radheshyam Pal,
Arshad Farid, Roomah Javed, Farzad Taghizadeh‑Hesary, and Subhajit Mandal
Chapter 7 Correlation and Successive Role of Synbiotics to Manage Blood Pressure.................................................. 103
Himanshu Sharma, Monika Kaushik, Venishaa S, Rashmi Pathak, Arshad Farid,
and Mithun Bhowmick
Chapter 8 Synbiotics: A Novel Paradigm for Phenylketonuria Management by Targeting
Gut–Microbiota and Gut–Brain Axes........................................................................................................... 121
Sana Fatima, Muhammad Muzammal, Shaista Naz, Muzammil Ahmad Khan,
Alamgir Khan, Arshad Farid, and Wasim Shah
Chapter 9 Synbiotic: Potential Role in Hemochromatosis Management....................................................................... 135
Monika Kaushik, Himanshu Sharma, Prathap Madeswaraguptha,
Venishaa S., Murugesan, and Vananga Mudi
v
vi Contents
Chapter 10 Correlation between Synbiotic Supplements and Lipid Metabolism:
A Novel Strategy to Counter‑Attack Metabolic Disorders........................................................................... 151
Alamgir Khan, Arshad Farid, Fazal Haq, Sohail Ahmad, Amin Ullah,
Muhammad Muzammal, and Muhammad Ajmal Khan
Chapter 11 Probiotics, Prebiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota........................... 160
Priyanka Ray, Mohammad Abdul Faseeh, Debojyoti Adak, and Himanshu Sharma
Chapter 12 Impact of Bacterial Metabolites on the Gut Environment to Manage Metabolic Disorders........................ 173
Sohail Ahmad, Maria Faraz, Muhammad Badar, Alamgir Khan, Roomah Javed,
and Arshad Farid
Chapter 13 The Potential Role of Prebiotics, Probiotics, and Synbiotics in Cancer Prevention
and Therapy................................................................................................................................................... 191
Phool Chandra, Himanshu Sharma, and Neetu Sachan
Chapter 14 Key Regulatory Aspects of Prebiotics, Probiotics, and Synbiotics in the Management
of Metabolic Disorders.................................................................................................................................. 214
Innocent Ayesiga, Shabnoor Iqbal, Yusuf Kyejjusa, Joash Okoboi, Timothy Omara,
Thomas Adelina, Delafrique Deogratias, Arthur Amule Anyole, Braize Ben Kagimu,
Denis Odongo, and Ivan Kahwa
Chapter 15 Synbiotics: Present Status and Future Prospectives to Control Metabolic Disorders................................... 245
Sanzia Mehjabin, Md. Khokon Miah Akanda, A. H. M. Nazmul Hasan,
and G. M. Masud Parvez
Index................................................................................................................................................................................... 257
Contributors
Debojyoti Adak Yusuf Asad
Department of Regulatory Affairs Biomedical Engineering Program, Department of
Quest Vitamins, Middle East FZE Dubai, United Arab Electrical and Computer Engineering
Emirates North Dakota State University
Fargo, North Dakota
Thomas Adelina
Department of Medicinal Chemistry and Pharmacognosy, Sumel Ashique
School of Pharmacy Department of Pharmaceutical Sciences
Catholic University of Health and Allied Sciences Bengal College of Pharmaceutical Sciences & Research
Mwanza, Tanzania Durgapur, India
Mohit Agrawal Innocent Ayesiga
School of Medical & Allied Sciences Ubora Foundation Africa
K.R. Mangalam University Kampala, Uganda
Gurugram, India
Muhammad Badar
Asad Ahmad Gomal Center of Biochemistry and Biotechnology
Faculty of Pharmacy Gomal University
Integral University Lucknow Dera Ismail Khan, Pakistan
Lucknow, India
Badruddeen
Mohammad Ahmad Faculty of Pharmacy
Faculty of Pharmacy Integral University Lucknow
Integral University Lucknow Lucknow, India
Lucknow, India
Mithun Bhowmick
Sohail Ahmad Department of Pharmaceutical Sciences
Gomal Center of Biochemistry and Biotechnology Bengal College of Pharmaceutical Sciences & Research
Gomal University Durgapur, India
Dera Ismail Khan, Pakistan
Pratibha Bhowmick
Usama Ahmad Department of Pharmaceutical Sciences
Faculty of Pharmacy Bengal College of Pharmaceutical Sciences & Research
Integral University Lucknow Durgapur, India
Lucknow, India
Phool Chandra
Md. Khokon Miah Akanda Teerthanker Mahaveer College of Pharmacy
Department of Pharmacy Teerthanker Mahaveer University
University of Asia Pacific Moradabad, India
Dhaka, Bangladesh
Hema Chaudhary
Juber Akhtar School of Medical & Allied Sciences
Faculty of Pharmacy K.R. Mangalam University
Integral University Lucknow Gurugram, India
Lucknow, India
Delafrique Deogratias
Arthur Amule Anyole Department of Pharmaceutical Sciences, Faculty of
Department of Pharmaceutical Sciences, Faculty of Medicine
Medicine Mbarara University of Science and Technology
Mbarara University of Science and Technology Mbarara, Uganda
Mbarara, Uganda
vii
viii Contributors
Maria Faraz Roomah Javed
Gomal Center of Biochemistry and Biotechnology Gomal Center of Biochemistry and Biotechnology
Gomal University Gomal University
Dera Ismail Khan, Pakistan Dera Ismail Khan, Pakistan
Arshad Farid Braize Ben Kagimu
Gomal Center of Biochemistry and Biotechnology Department of Pharmaceutical Sciences, Faculty of
Gomal University Medicine
Dera Ismail Khan, Pakistan Mbarara University of Science and Technology
Mbarara, Uganda
Mohammad Abdul Faseeh
Department of Biopharmaceutics Ivan Kahwa
Quest Vitamins, Middle East FZE, Dubai, United Arab Department of Pharmacy, Faculty of Medicine
Emirates and
Pharm‑Bio Technology and Traditional Medicine Centre
Sana Fatima of Excellence
Gomal Center of Biochemistry and Biotechnology Mbarara University of Science and Technology
Gomal University Mbarara, Uganda
Dera Ismail Khan, Pakistan
Monika Kaushik
Nandani Goyal Amity Institute of Pharmacy
Department of Nutrition and Nutraceutical Amity University Madhya Pradesh
Dr Reddy`s Laboratories Limited Gwalior, India
New Delhi, India
Alamgir Khan
Prakash Chandra Gupta Gomal Center of Biochemistry and Biotechnology
School of Pharmaceutical Sciences Gomal University
Chhatrapati Shahu Ji Maharaj University Dera Ismail Khan, Pakistan
Kalyanpur, India
Mohammad Irfan Khan
Fazal Haq Faculty of Pharmacy
Institute of Chemical Sciences Integral University Lucknow
Gomal University Lucknow, India
Dera Ismail Khan, Pakistan
Muhammad Ajmal Khan
Shabnoor Iqbal School of Medicine
Department of Pharmacology University of Maryland
University of the Free State Baltimore, Maryland
Bloemfontein, South Africa
Muzammil Ahmad Khan
Anas Islam Gomal Center of Biochemistry and Biotechnology
Faculty of Pharmacy Gomal University
Integral University Lucknow Dera Ismail Khan, Pakistan
Lucknow, India
Akash Kumar
Aarzoo Jangra Department of Food Technology
Department of Food Technology SRM University Delhi‑NCR
SRM University Delhi‑NCR Sonepat, India
Sonepat, India
Ashok Kumar
Yash Jasoria Department of Internal Medicine
School of Medical & Allied Sciences University of Kansas Medical Center
K.R. Mangalam University Kansas City, Kansas
Gurugram, India
Contributors ix
Mukesh Kumar Denis Odongo
Department of Food Technology Department of Pharmaceutical Sciences, Faculty of
Guru Jambheshwar University of Science and Technology Medicine
(GJUS&T) Mbarara University of Science and Technology
Hisar, India Mbarara, Uganda
Sanjesh Kumar Joash Okoboi
Department of Pharmacology Department of Biochemistry, School of Health Sciences
Institute of Pharmaceutical Research, GLA University Soroti University
Mathura Soroti, Uganda
Mathura, India
Timothy Omara
Yusuf Kyejjusa Department of Chemistry, College of Natural Sciences
Department of Chemistry and Biochemistry, Faculty of Makerere University
Science Kampala, Uganda
Islamic University in Uganda
Mbale, Uganda Radheshyam Pal
and Department of Pharmacology
Department of Chemistry, Faculty of Science Pandaveswar School of Pharmacy
University of Lahore Pandaveswar, India
Lahore, Pakistan
G. M. Masud Parvez
Prathap Madeswaraguptha Department of Pharmaceutical and Biomedical Sciences,
Amity Institute of Pharmacy College of Pharmacy
Amity University Madhya Pradesh University of Georgia
Gwalior, India Athens, Georgia
Subhajit Mandal Kamla Pathak
Department of Pharmacology Faculty of Pharmacy
P.G. Institute of Medical Sciences Uttar Pradesh University of Medical Sciences
Chandrakona, India Saifai, India
Sanzia Mehjabin Rashmi Pathak
Department of Pharmacy Department of Pharmacy
Varendra University Invertis University
Rajshahi, Bangladesh Bareilly, India
Popat Mohite Bhupender Prajapati
AETs St. John Institute of Pharmacy and Research Shree S. K. Patel College of Pharmaceutical Education
Palghar, India and Research
Ganpat University
Muhammad Muzammal Mehsana, India
Gomal Center of Biochemistry and Biotechnology
Gomal University Jhilam Pramanik
Dera Ismail Khan, Pakistan Department of Food Technology
William Carey University
Shaista Naz Shillong, India
Gomal Center of Biochemistry and Biotechnology
Gomal University Abhijeet Puri
Dera Ismail Khan, Pakistan AETs St. John Institute of Pharmacy and Research
Palghar, India
A. H. M. Nazmul Hasan
Department of Pharmacy
University of Asia Pacific
Dhaka, Bangladesh
x Contributors
Priyanka Ray Navaneetha Krishnan Subramaniyan
Department of Pharmaceutics, Guru Nanak Institute of Department of Pharmaceutical Chemistry, Dr. Kalam
Pharmaceutical Science & Technology College of Pharmacy
Sodepur, Kolkata, India Thanjavur, India
Neetu Sachan Vijayaraj Surendran
Maharana Pratap College of Pharmacy Department of Pharmaceutical analysis, Dr. Kalam
Mandhana Kanpur College of Pharmacy
Kanpur, India Thanjavur, India
Wasim Shah Farzad Taghizadeh‑Hesary
Department of Life Science, University of Science and ENT and Head and Neck Research Center and Department
Technology of China The Five Senses Health Institute, School of Medicine, Iran
Anhui Province, China University of Medical Sciences
Tehran, Iran
Himanshu Sharma and
Teerthanker Mahaveer College of Pharmacy Clinical Oncology Department
Teerthanker Mahaveer University Iran University of Medical Sciences
Moradabad, India Tehran, Iran
Nisha Sharma Amin Ullah
School of Pharmaceutical Sciences Department of Health and Biological Sciences
Chhatrapati Shahu Ji Maharaj University Abasyn University Peshawar
Kalyanpur, India Peshawar, Pakistan
Aditya Singh Swarnakshi Upadhyay
Faculty of Pharmacy School of Pharmaceutical Sciences
Integral University Lucknow Chhatrapati Shahu Ji Maharaj University
Lucknow, India Kalyanpur, India
Sudarshan Singh Murugesan Vanangamudi
Office of Research Administration Amity Institute of Pharmacy
and Amity University Madhya Pradesh
Department of Pharmaceutical Sciences, Faculty of Gwalior, India
Pharmacy
Chiang Mai University S. Venishaa
Chiang Mai, Thailand Department of Nanoscience and Technology
Bharathiar University
Bhagavathi Sundaram Sivamaruthi Coimbatore, India
Office of Research Administration
Chiang Mai University
Chiang Mai, Thailand
and
Innovation Centre for Holistic Health, Nutraceuticals, and
Cosmeceuticals
Faculty of Pharmacy, Chiang Mai University
Chiang Mai, Thailand
About the Editors
Dr. Neeraj Mishra has been working as a Professor at Amity Dr. Arshad Farid is a distinguished academic and
Institute of Pharmacy, Gwalior, since July 2019. He has around researcher with a prolific career spanning over 15 years
20 years of teaching and research experience. He has more than in teaching and research. He is currently serving as an
100 publications of international and national repute on recent Assistant Professor in the Gomal Center of Biochemistry
concepts of novel drug delivery systems, oral delivery of syn‑ and Biotechnology at Gomal University, Pakistan. He
biotics, localized drug delivery, and targeted and controlled completed his Ph.D. in Biotechnology from the Centre of
drug delivery of nanocarriers and microparticles for the treat‑ Biotechnology and Microbiology (COBAM), University
ment of breast, colon, and neurodegenerative disorders. He has of Peshawar, Pakistan. His remarkable achievements have
also edited 10 books and authored 25 book chapters. He has garnered him international recognition, as evidenced
been granted three international patents and two Indian pat‑ by his selection for the British Council‑Charles Wallace
ents. Dr. Mishra is the recipient of the “Distinguished Professor Fellowship program for the academic year 2022–2023.
Award” 2019 from DST‑NSTMIS, SPAICS, Indore, and M.P. in In 2007, he was also awarded a prestigious scholarship
September 2019. Dr. Mishra has also received the “Outstanding to the University of Glasgow, UK, funded by the Higher
Scientist Award” 2020, 6th International Scientist Awards Education Commission (HEC) of Pakistan. He has authored
on Engineering, Science, and Medicine, 20–21 June 2020, or co‑authored more than 70 research papers and has been
Chennai, India. Dr. Mishra has received the “Distinguished granted nine patents.
Professor Award” 2021 from the Indian Pharmaceutical
Association, MP State Branch, Indore. Dr. Mishra has received Dr. Ashish Garg obtained a B.Pharm. in 2011 and a
the “Best Academician Award” in the Indian Pharmacy M.Pharm. in 2013 from Guru Ramdas Khalsa Institute
Graduate Association, M.P. State International Conference of Science and Technology, Pharmacy, Jabalpur, M.P.,
held on May 6, 2023, at DAVV Auditorium, Indore, India. India. He has pursued his Ph.D. from SRK University,
M.P. He has over 10 years of experience in both teaching
Dr. Sumel Ashique has been working as an Assistant Professor and research. He has authored more than 100 research
at the Department of Pharmaceutical Sciences, Bengal College and review articles published in national and international
of Pharmaceutical Sciences & Research, Durgapur 713212, journals of high repute. Additionally, he has edited ten
West Bengal, India. He has 3.5 years of teaching experience books and been awarded three patents and one design pat‑
and has published more than 50 research studies and review ent. He is presently working as an Associate Professor in
articles in internationally and nationally accredited, reputed the Department of Pharmaceutics at Guru Ramdas Khalsa
journals. He has been working in targeted drug delivery, nan‑ Institute of Science and Technology, Jabalpur, Madhya
otechnology, and gut microbiome. He has also been granted Pradesh, India.
5 patents from IP and Australia, and has authored more than
20 book chapters. He has edited 5 books under CRC Press,
Springer, Wiley, and Taylor‑Francis Publisher.
xi
1 An Introduction on
Metabolic Disorders
Yash Jasoria, Mohit Agrawal, and Hema Chaudhary
1.1 INTRODUCTION obesity, and diabetes has been the subject of much discus‑
sion. A symposium on the present level of knowledge on
An imbalance in the body’s distribution and metabolism these important public health concerns was arranged by
of macronutrients, such as proteins, lipids, and carbs, is the NIEHS Division of the National Toxicology Program.
referred to as a metabolic disease. Metabolic disorders Multiple exposures to the environment and T2DM were
can arise when abnormal chemical interactions disturb the shown to be linked, according to an assessment of the
body’s normal metabolic function. It can alternatively be body of research. Additionally, there was evidence for the
described as an inherited single gene aberration, most of “developmental obesogen” theory, which postulates that
which are autosomal recessive. Weight gain, type 2 diabe‑ exposure to chemicals may change the way adipocytes dif‑
tes mellitus (T2DM), and inflammatory bowel disorders ferentiate or how brain circuits that control food behavior
are among the metabolic conditions that are most prevalent develop, hence raising the risk of obesity. The effects may
globally. A genetic abnormality that results in an insuffi‑ be most evident if one follows a diet heavy in fat, carbs,
cient amount of an enzyme is known as an inherited met‑ or calories is followed later in life along with the growing
abolic disease. Inborn errors of metabolism are the term exposure. There is relatively little data on the relationship
used to describe these disorders, of which there are sev‑ between type 1 diabetes and exposure to environmental
eral kinds. When the pancreas or liver are not functioning chemicals(Thayer et al., 2012). In the European Union (EU),
correctly, metabolic disorders can also arise (Zakir et al., diabetes and obesity are on the rise. It is becoming more
2022). Individuals who have problems with the metabolism widely acknowledged that endocrine‑disrupting chemical
of tiny molecules may first exhibit acute sickness. Every (EDC) exposure has a role, separate and apart from physi‑
kid experiencing a sudden illness in which an underlying cal exercise and nutrition (Legler et al., 2015). Numerous
metabolic issue might be present should have basic labo‑ studies and acknowledgments indicate that throughout the
ratory testing completed. Slowly progressing encephalopa‑ last several decades, the prevalence of diabetes has grown
thies and systemic symptoms are typically seen in patients in both low‑ and middle‑income nations and high‑income
with metabolic abnormalities affecting a whole organelle. countries. Diabetes’s global impact is unknown, especially
A variety of bodily fluids include chemicals that can be uti‑ in low‑ and middle‑income nations (Seuring et al., 2015).
lized to assess the effectiveness of therapy as well as serve Mammalian populations have experienced significant
as indications of the existence and advancement of certain and persistent increases in body weight, similar to what
metabolic diseases (Guerrero et al., 2018). Genetics, dietary has happened to human populations. This is true even in
modifications, physical activity, and aging have all been the absence of the factors that are generally thought to be
connected to the current epidemics of metabolic diseases, the main causes of the obesity epidemic in humans due
which include obesity, T2DM, liver lipid problems, and to their effects on diet and physical activity (Klimentidis
metabolic syndrome. The prevalence of these metabolic et al., 2011).
disorders is rising quickly, but there is also strong evidence According to Trasande et al. (2012), there are many met‑
that other environmental variables could also be involved abolic systems that bisphenol A exposure can affect. This
(Heindel et al., 2017). implies that exposure to bisphenol A at levels relevant to
the environment may cause an increase in body mass and
1.2 LIST OF METABOLIC DISORDER consequently lead to obesity in humans. Adult studies have
recently looked into this idea. The skyrocketing costs of
1.2.1 Obesity health care associated with treating co‑morbidities associ‑
There are health hazards linked to obesity. In adults, the ated with obesity‑related conditions include dyslipidemia,
prevalence of obesity was a little over 36% in 2011, whereas hyperglycemia, hypertension, liver and gallbladder disor‑
in children, it was 17%. In comparison to males (34.3%), ders, insulin resistance, and T2DM (Legler et al., 2015).
women (38.3%) had a greater prevalence of obesity. There Obesity is also associated with neurological problems, can‑
was no discernible sex difference among all the youngsters cer, and obstructive sleep apnea. Determining the causes of
(Ogden et al., 2015). The hypothesis that exposure to envi‑ obesity has therefore grown to be a significant public health
ronmental pollutants has a role in the rising prevalence of concern (Heindel et al., 2017).
DOI: 10.1201/9781032702438-11
2 Synbiotics in Metabolic Disorders
1.2.2 Type 2 Diabetes sickness that advance. One of the hallmarks of steatohepa‑
titis is hepatocellular membrane damage and inflammation.
Diabetes is another form of metabolic disease, which is Among young people, NAFLD is one of the most frequent
characterized by elevated blood sugar levels brought on by causes of persistent liver disease (Anderson et al., 2015).
deficiencies in either or both of the actions or production Clinically, dyslipidemia, hypertriglyceridemia, insulin
of insulin. Long‑term harm, malfunction, and failure of resistance, high blood pressure, and/or T2DM are common
several organs, including the kidneys, eyes, nerves, heart, in people with NAFLD, and they are all risk factors for
and blood vessels, are linked to diabetes’s persistent hyper‑ CVDs. In actuality, NAFLD is rather common in people
glycemia (American Diabetes Association, 2010). Some who have elements of MetS. More than 76% of people with
of the elements that lead to the decrease in insulin action T2DM, for example, have been observed to have NAFLD.
known as insulin resistance include an increase in inflam‑ Furthermore, NAFLD is present in more than 90% of indi‑
matory signaling, the activation of endoplasmic reticulum viduals who are extremely obese and undergoing bariatric
(ER) stress pathways, and the direct damage that excess lip‑ surgery. NAFLD patients have many risk factors for CVD,
ids and other metabolic fuels bring to organs and tissues. which makes CVD‑related mortality one of the primary
A metabolic component to the malfunctioning of β‑cells causes of death for these individuals. The incidence of
observed in T2DM is addressed. The typical increase in NAFLD was determined using a selected group of studies
pyruvate cycling caused by glucose is inhibited by exces‑ that monitored healthy nondrinkers for the development of
sive lipid exposure (Muoio and Newgard, 2008). Diabetes NAFLD at baseline but did not have NAFLD. We included
type 2 has been associated with several environmental longitudinal studies of NAFLD patients to evaluate the
exposures. Evidence was also presented in support of the effects of hepatocellular carcinoma (HCV) on NAFLD
“developmental obesogen” theory, which suggests that outcomes, including liver‑related mortality, cardiac mortal‑
chemical exposure may change how the brain develops cir‑ ity, and total mortality. Histological progression was deter‑
cuits that control eating habits or the differentiation of adi‑ mined using liver samples (Younossi et al., 2016).
pocytes, which raises the risk of obesity. During later life,
the effects may be most apparent if a diet heavy in calories,
carbohydrates, or fat is combined with the growing expo‑ 1.2.4 Metabolic Syndrome
sure (Thayer et al., 2012). The metabolic syndrome is a group of metabolic disorders
Diabetes is expected to affect 2.8% of people globally in that includes insulin resistance, glucose intolerance, obe‑
2000 and 4.4% of people globally in all age categories by sity, dyslipidemia, hypertension, and hyperinsulinemia
2030. Between 2000 and 2030, there were 171 million more (Dallongeville et al., 2004). More than one in four persons
people worldwide estimated to have diabetes. Although in the US suffers from the metabolic syndrome, which has
diabetes affects males more frequently than women, more become epidemically common in contemporary culture.
women than men have the disorder. By 2000 and 2030, the More than 20 years ago, it was believed that insulin resis‑
number of people living in cities in emerging nations is tance was a major factor in the development of the meta‑
expected to double. It appears that the rise in the percentage bolic syndrome. There has been a great deal of conversation
of adults over 65 is the most significant demographic shift about the part that insulin resistance plays in the metabolic
affecting diabetes prevalence worldwide (Wild et al., 2004). syndrome. Atherosclerosis, cholesterol gallstones, and
One of the main controllable risk factors for T2DM is increased biliary cholesterol production can all result from
obesity. Obesity and diabetes are linked to a higher risk insulin resistance alone, in addition to glucose intolerance.
of death, especially from cardiovascular disease (CVD). This contends that, contrary to what some experts have
Increased rates of type II diabetes, dyslipidemia, hyperten‑ said, the metabolic syndrome is more than just a group of
sion, acid reflux disease, and several cancers have also been problems that need to be taken into account and managed
associated with being overweight. The high proportion of separately. In actuality, the metabolic syndrome is a condi‑
obese people with diabetes suggests that more should be tion in which a common pathophysiological disturbance—
done to reduce obesity because it can be changed to reduce insulin resistance—is the cause of many, but not all, of its
the chance of developing diabetes. In addition to treating components (Haas and Biddinger, 2009).
obesity medically and surgically, these initiatives should
focus on obesity prevention. One of the biggest studies on
purposeful weight loss among diabetes is the look AHEAD 1.3 THE ROLE OF GENETICS IN
experiment (Nguyen et al., 2011). METABOLIC DISORDERS
1.3.1 Role of Genetics Factors in Obesity
1.2.3 NAFLD and Hyperlipidemia
The “obesogenic environment” and alterations in lifestyle
The non‑alcoholic fatty liver disease, or “NAFLD,” refers to that have led to more availability to calories and less energy
a buildup of fat in the liver that is not brought on by chronic expenditure have been emphasized in the hunt for explana‑
liver disease or heavy alcohol consumption. Steatosis, tions of the current obesity pandemic. Long acknowledged
fibrosis, and finally cirrhosis are the stages of this spectrum are the genetic components of obesity, but genetics is also
An Introduction on Metabolic Disorders 3
playing a bigger role in this relatively quick transforma‑ factors. A significant genetic component to T2DM is also
tion in the population. Analysis of genetic components in suggested by a wealth of research (Lyssenko and Laakso,
unprecedented depth has been made possible by the tech‑ 2013). According to the findings of twin studies, the
nological revolution in genotyping that has coincided with heritability of T2D is thought to vary from 30% to 70%.
the obesity pandemic. This includes examining the role of Nearly 70 loci for T2D have been found by genome‑wide
several genetic factors in more prevalent types of obesity, as association studies (GWASs) since the development of
well as single genes that cause unusual forms of the disease high‑throughput genotyping methods. On the other hand,
(Waalen, 2014). A genome‑wide association research and the impact of a single locus on T2D is quite small, and the
a Metabochip meta‑analysis of body mass index (BMI), a heredity of T2D appears to be partially accounted for by
metric frequently used to quantify adiposity and define obe‑ all observed loci. Geneticists are becoming mystified about
sity in up to over 3 lakh individuals, were employed in an T2D, which was formerly referred to as their nightmare or
examination into the genetic foundations of obesity (Locke headache. Investigative work is currently being done to try
et al., 2015). As per Speliotes et al. (2010), 2.8 million single and unravel this riddle by finding unusual or low‑frequency
nucleotide polymorphisms (SNPs) in a maximum of 123,865 genetic variations with greater impacts. Another problem
people were demonstrated to be associated with BMI, so is that it is very impossible to connect genetic variations
serving as genetic markers for predisposition to obesity. linked to disease pathogenesis since most genetic vari‑
Up to 125,931 more individuals had focused follow‑up on ants found by GWAS are found in non‑coding areas of the
42 SNPs. identified 18 new loci (P < 5 × 10 −8) connected to genome (Hara et al., 2014).
BMI, one of which contains a copy number variation near
GPRC5B, and verified the existence of 14 previously iden‑
tified loci linked to obesity susceptibility. MC4R, POMC, 1.3.3 Role of Genetic Factors in Lipid
SH2B1, BDNF, and other critical hypothalamic regulators Disorder Metabolism
of energy balance map in close proximity to the incretin
receptor GIPR. Further insights into the regulation of body It is uncertain that both heredity and environment affect
weight in humans may come from examining genes found blood lipid levels. Age appears to have less of an impact
in recently related loci. on some blood lipids than on others due to hereditary vari‑
Very few types of obesity are known to have single gene ables. Though its impact on other blood lipids and apolipo‑
mutations or chromosomal abnormalities, such as those proteins appears to be smaller in the elderly, early infancy
causing Prader–Willi and Bardet–Biedl syndromes. These seems to have a significant role in predicting total choles‑
types of obesity are often signs of genetic diseases. It is terol levels later in life (Heller et al., 1993). It is uncertain
hypothesized that additional environmental variables might how much heredity and environmental factors affect blood
alter these genetic predispositions because many individu‑ lipid levels. Age appears to have less of an impact on some
als who contain genetic variations associated to elevated blood lipids than on others due to hereditary variables.
BMI are not fat (Goldstone and Beales, 2008). Though its impact on other blood lipids and apolipoproteins
appears to be smaller in the elderly, early infancy seems
to have a significant role in predicting total cholesterol
1.3.2 Role of Genetic Factors in Diabetes levels later in life. A large‑scale, nationally representative
Genetic factors influence diabetes type 1 and type 2. The population‑based sample survey was used to demonstrate
highly polymorphic HLA class II genes that control the the strong connections between blood lipids and the poly‑
immune system are located in a region on chromosome 6 morphisms and haplotypes in ITGB3, PON1, and APOE
that accounts for more than half of the inherited susceptibil‑ across the three principal racial/ethnic groupings in the US
ity to insulin‑dependent diabetes mellitus. Diabetes suscep‑ population. Essential components that influence plasma
tibility and resistance are predicted by alleles of HLA‑DQβ, lipoprotein concentrations may shed light on the molecu‑
according to an analysis of the DNA sequences of diabet‑ lar processes controlling blood lipid and cholesterol levels
ics. Additionally, the autoimmune response to the islet cells (Chang et al., 2010).
that produce insulin is characterized by residue 57 of the A deficiency in low‑density lipoprotein receptor (LDLR)
β‑chain, which is a component of the DQ molecule (Todd endocytosis unique to a particular cell type is the hallmark
et al., 1987). For more than 30 years, clinical indicators, dia‑ of autosomal recessive hypercholesterolemia. Individuals
betes‑associated autoantibodies, family history, and genetic with this illness have decreased liver LDLR‑mediated
risk factors have been used to describe people with T1D. absorption of low‑density lipoproteins (LDL), but normal
More than 20 additional genetic variations linked to type 1 fibroblast function is unaffected (Garuti et al., 2005).
diabetes have been found through whole‑genome research Dyslipidemia is a clinical condition commonly observed
(Vehik et al., 2013). as the primary risk factor for cardiovascular ailments.
More than 90% of cases of the illness are T2DM, which Dyslipidemias have a substantial hereditary component,
is rapidly increasing in both prevalence and incidence even though secondary variables may contribute to their
around the world. Diabetes type 2 is an incurable condition clinical presentation. The genes encoding for proteins
brought on by a confluence of hereditary and environmental that interact with the LDLR, such as APOB, PCSK9, and
