BASIC OBESITY MANAGEMENT ACCREDITATION 3

https://doi.org/10.33591/sfp.49.9.u1

Unit No. 1
UNDERSTANDING OBESITY: HOW AND WHY?
Dr Tham Kwang Wei, Dr Lam Chih Chiang Benjamin

ABSTRACT understanding that beyond the passive accumulation of

Obesity is currently recognised as a chronic disease excess energy as adiposity, obesity is a chronic, often
that is often relapsing and progressive. This relapsing and progressive disease resulting from a multitude
requires attention for long-term monitoring to
treat or prevent obesity-related complications. This
of factors. It has also led to weight bias and obesity stigma
article discusses the biology of weight regulation against people living with obesity (PwO), including by
as a basis for understanding obesity as a disease, healthcare professionals (HCPs).4 Despite being at further
and to appreciate the complex and multifactorial risk of many obesity-related diseases, PwO often do not seek
pathogenesis of obesity. With this understanding medical attention early, and the weight bias by HCPs also
of the factors involved in perpetuating obesity in impedes them from providing quality care.4
different individuals, the approach to patients with
obesity should be as comprehensive and systematic as As with many chronic diseases, the pathogenesis of obesity
with other chronic diseases. Management strategies
and treatment plans, which need to have long-term
involves many roots (aetiologies and associated factors).
weight maintenance and weight regain prevention in We now understand that there is a complex interplay of
mind, can be more individualised for patients with physiologic, genetic, epigenetic, and developmental factors
obesity. with variables of behavioural, psychological, socioeconomic,
medications, and environmental ones, both intrinsic and
SFP2023; 49(9): 6-11 extrinsic, leading to the pathogenesis and perpetuation of
obesity.5 Only by addressing these roots and understanding
Keywords: Obesity, chronic disease, pathogenesis, obesity as a chronic condition can we adequately manage
body weight regulation, weight maintenance and prevent obesity and its multitude of associated costly
comorbidities.4,5
INTRODUCTION
BIOLOGY OF WEIGHT REGULATION
Over the last 40 years, the prevalence of obesity has risen
substantially in almost all world regions, such that there are The body’s adipose tissue represents energy stores to survive
now more than 600 million obese adults and 100 million energy-scarce conditions. Hence, it would not be surprising
obese children worldwide.1 This increasing burden of obesity that that body weight (or more accurately, adipose tissue
has been identified in Singapore and other Asia-Pacific in the body) is tightly regulated by an extremely complex
countries.2 From 1992 to 2010, the prevalence of obesity neuroendocrine energy balance circuitry. This circuitry is
more than doubled from 5.1 percent to 10.8 percent. A composed of specific nuclei in various brain regions, most
parallel rise in the prevalence of diabetes mellitus has also prominently the hypothalamic arcuate nucleus (ARC), the
been seen, reflecting the burden of obesity.3 Based on body paraventricular nucleus, the lateral hypothalamic area, and
mass index (BMI) categories that indicate increased health the nucleus of the solitary tract of the hindbrain (refer to
risks in Asian populations, 52.5 percent of Singaporeans Figure 1).6,7
have a BMI in the moderate- to high-risk groups
Under relatively constant environmental conditions, this
(>23.0 kg/m2), heralding the potential for a greater burden
regulatory system senses and processes various metabolic
of adiposity-related comorbidities in Singapore.3
signals regarding the current energetic status and adjusts
Obesity has often been viewed as a result of a simple lack the metabolic responses to maintain a stable weight without
of self-discipline and willpower to “eat less and move more” conscious control.6 This homeostatic regulation of body
or plain laziness on the part of the person with obesity.4 weight is similar to that of other physiologic parameters,
This oversimplified perception results from the lack of such as body temperature, blood pressure or blood glucose,
where a “set point” seems to exist and deviation from this
“set point” elicits a compensatory response in the opposite
direction to restore this “set point”. Therefore, weight
DR THAM KWANG WEI
regains after weight loss is actually physiological8,9 and not
Senior Consultant Endocrinologist
President, Singapore Association for the Study of Obesity necessarily due to a failure of conscious efforts (to lose
weight). For example, energy expenditure is reduced in
DR LAM CHIH CHIANG BENJAMIN response to weight loss, in an effort to resist further weight
Senior Consultant loss so that the “set point” can eventually be restored.
Family and Community Medicine, Khoo Teck Puat Hospital However, in PwO, it has been observed that such responses
Vice-President, Singapore Association for the Study of can go beyond what is expected of the weight loss, and
Obesity based on experimental data, these responses can even persist
for years despite weight regain, further predisposing the
individual to further weight (re)gain.5,8,9

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 UNDERSTANDING OBESITY: HOW AND WHY?

Figure 1. Model for regulation of the hindbrain presence of a combination of various gene alleles (giving rise
response7 to a high polygenic risk score) and epigenetic factors make
one susceptible to weight gain in a conducive obesogenic
environment (gene-environment interaction).11,14

Maternal obesity, malnutrition, gestational weight gain, or

weight loss, especially in early pregnancy, have been found
to result in childhood adiposity, adverse cardiometabolic
profiles, and insulin resistance, which may persist into
adulthood.15 The adverse effect of maternal obesity and
metabolic ill-health on offspring have been postulated to
be mediated through epigenetic modifications, which alter
gene function without any DNA defects.11 In the Growing
Up in Singapore Towards healthy Outcomes (GUSTO)
study involving a cohort of nearly 1,000 mother-offspring
sets, greater maternal adiposity and higher polygenic risk
scores linked to maternal obesity were associated with higher
Additionally, a different set of neuroendocrine signals guide birth weights and early childhood adiposity. This suggests
food intake based upon the reward value of the food, also that prenatal genetic influences and epigenetic factors can
known as the reward or “hedonic” system.6,10 The brain influence childhood adiposity, which can be lasting.16 Intra-
regions responsible for this reward system are dispersed uterine exposure to endocrine-disrupting chemicals has also
in the corticolimbic structures. A primary characteristic been postulated to be associated with childhood obesity.5
of this system is its ability to override the signals from Environmental and lifestyle factors favouring a positive
the homeostatic circuits as described.6 Hence, the reward energy balance and weight gain include increasing per
system is non-homeostatic regarding energy balance. This capita food supplies and consumption, particularly of
system integrates basic midbrain and hindbrain functions highly processed, energy-dense, and palatable foods that are
with more complex cortical functions involving arousal at often served in large portions. These factors are influenced
the sight of palatable food items and the procurement of by one’s socioeconomic situation, such as decreasing time
food, mediating the “liking” (level of pleasure or reward) spent in occupational physical activities, displacement of
and “wanting” (the motivation or drive to consume food), leisure-time physical activities with sedentary activities such
which are subconscious processes.6 In human studies, as television watching, use of electronic devices, growing use
functional MRI (fMRI) studies have shown overactivation of medicines that have weight gain as a side effect, stress,
of reward-encoding brain regions and/or deficiency in and inadequate sleep.11 More recent studies have identified a
cortical inhibitory networks in PwO.6,10 potential role for the gut’s microbial content in determining
a broad range of metabolic abnormalities, including
OBESITY AS A DISEASE: ABNORMAL obesity.17,18 The evidence supporting causation includes
PHYSIOLOGY AND ROOTS OF OBESITY animal studies that show that obesity, as a phenotype, is
transmittable via the transfer of gut microbiota from the
With the understanding of the biology of weight regulation,
obese (mice/humans) to germ-free mice,19,20 and mechanistic
obesity is now understood to signify abnormal physiology
studies that demonstrate the possible mechanisms linking
whereby there has been a surplus intake of energy and
the gut microbiota with obesity.17,21
an elevated body weight set point is now defended.5,8,9
A mismatch of as little as 3 percent can lead to a weight Apart from the mentioned factors mentioned that are linked
gain of 1-2 kg per year and, if persistent over the years, can to the pathogenesis of obesity, numerous other factors
ultimately result in severe obesity.5 The factors are known to contribute to or exacerbate obesity and may lead to the
cause this are complex and multiple. They range from genetic attenuation of obesity treatment (refer to Figure 2). These
to socioeconomic to environmental and emotional factors should also be considered and adequately addressed when
that are well-known to be potent modulators of appetite assessing and managing patients with obesity.22
and energy expenditure.7 Twin, family, and adoption studies
show that the rate of heritability of BMI is high, ranging
OBESITY AS A DISEASE: HEALTH
from 40 to 70 percent,11 demonstrating a major genetic CONSEQUENCES
component. In addition to syndromic and monogenic
forms of obesity (e.g., MC4R mutations, leptin deficiency), Obesity is not benign. The failure of adipose tissues to
which account for less than 5 percent of general obesity continually expand lead to pathological changes in the
in adults, genome-wide association studies (GWAS) have adipose tissue, which is characterised by macrophage invasion
identified more than 700 independent loci associated with and/or increased release of pro-inflammatory adipokines
BMI and/or obesity without.12-14 These, however, attribute and decreased release of anti-inflammatory adipokines such
to less than 5 percent of the inter-individual variation in as adiponectin (refer to Figure 3).23 In addition, this failure
BMI and traits linked to obesity. It is more likely that the to further expand and act as a “metabolic sink” results in

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UNDERSTANDING OBESITY: HOW AND WHY?

Figure 2. ROOTS of Obesity Fact Sheet. World Obesity Federation 202122

harmful ectopic fat deposition in lean tissues such as the Figure 3. Pathological changes in adipose tissue23
heart, liver, pancreas, and kidneys.23 These two phenomena
contribute to a pro-inflammatory and insulin-resistant
milieu, giving rise to metabolic complications such as type
2 diabetes mellitus (T2DM), non-alcoholic fatty liver
disease (NAFLD), and cardiovascular disease (CVD).23,24
Additionally, the mechanical forces resulting from excessive
adipose tissue can give rise to biomechanical consequences
(such as Obstructive Sleep Apnoea (OSA) and low back
pain), and obesity as a condition has been associated with
various psychosocial issues, impacting on mental health.25

All these adverse consequences affect the quality of life,

increase healthcare costs, and increase mortality.26 Therefore,
based on the current knowledge that the development of
obesity results from abnormal physiology, with attending
health consequences (complications, morbidities, and
mortality), obesity fulfils the criteria for a disease state and
is now determined to be a disease27 rather than just a lifestyle
risk factor. Several associations and organisations, including
the World Health Organisation (WHO), have now declared
obesity as a disease (refer to Figure 4). This is an important
first step to tackling the problem of obesity, which has
emerged as an epidemic that poses an unprecedented public
health challenge.27

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 UNDERSTANDING OBESITY: HOW AND WHY?

Figure 4. Organisations that have declared obesity in a 0.5 kg/week weight loss indefinitely, because this
as a disease27 calculation does not consider the homeostatic mechanisms
that will resist further weight loss, and in fact, will conspire
to regain weight to restore the original “set point”.8,9,30 It is
also important to note that the same diet and exercise plan
(often prescribed once in the beginning) will not suffice to
maintain that 500 kcal deficit per day as a declining weight
will mean declining energy expenditure.5,30 Nonetheless, the
point here is that asking all obese people to just “eat less and
exercise more” overly simplifies the obesity problem.4,27

Understanding the biology of weight regulation and the

appreciation of the complex and multifactorial nature of
how this regulation can go wrong resulting in obesity would
indicate that there is no one-size-fits-all intervention or
solution.31 Considering the different (roots) factors that
lead to weight gain in different individuals (e.g., sleep
disruption in one patient, stress-eating or medications
causing weight gain in another) would necessitate a multi-
level and individualised multi-pronged approach to treating
obesity. Multi-level, apart from the individual, would
include the social and community, physical (environment),
and economic levels of interventions31, while a multi-
APPROACH TO MANAGEMENT OF OBESITY pronged approach at the individual level would encompass
AS A DISEASE AND ITS COMPLICATIONS not just the lifestyle and behavioural modifications but also
the possible combination with pharmacologic and even
Recognising obesity as a disease is a pertinent first step in
bariatric surgical procedures based on individualised risk-
the management of PwO. This will aid assessment using
benefit assessment.28,32,33
a systematic approach similar to how we approach any
chronic disease and devise management plans from an Since obesity is a chronic, often relapsing and progressive
aetiologic perspective.22,27 As with any disease state, its disease, weight regain (“relapse”) after weight loss is
management requires an understanding of how severe common, in part consequent to the physiologic counter-
the disease is.28 For obesity, management guidelines have response to negative energy balance. Long-term follow-
slowly moved from a BMI-centric approach, where the up for monitoring of weight regains and obesity-related
goal of therapy is to lose a given amount of weight (e.g., comorbidities is necessary and prudent.28,32 Management
5-10 percent) to a complications-centric approach, where strategies for weight maintenance/weight regain prevention
weight is no longer the major determinant of appropriate of at least 6-12 months should be considered during weight
treatment, but now based on the risk, presence, and severity loss treatment, understanding that there is also reduced
of obesity-related complications.28,29 For example, at least adherence to lifestyle changes with time.30,33 Some of these
10 percent weight loss is needed to improve NAFLD and measures may involve staying in frequent contact with the
OSA significantly.28,29 Hence, for a person with multiple patient even after weight loss is attained (e.g., once a month),
complications, including NAFLD and OSA, modest weight long-term use of anti-obesity medications, initiation of
loss (defined as 5-10 percent weight loss) may be inadequate, anti-obesity medications after weight plateau with lifestyle
and more aggressive treatment options effecting more than changes, and/or intermittent use of very low- or low-calorie
modest weight loss need to be considered. Although more diets.30,32,33
aggressive treatment may involve higher risk, the benefit of
treating the various obesity-related complications should Obesity stigma and discrimination that PwO face can be
outweigh this risk. Therefore, the main goal of therapy now pervasive and poses an often unrecognised detrimental
is to treat or prevent obesity-related complications, rather effect on their mental and physical health. This extends
than to purely lose weight per se.28 to the workplace, schools, healthcare settings, and social
circles. As HCPs, understanding obesity as a disease and
IMPORTANCE OF A MULTI-LEVEL AND its causes (roots) and refraining from using language
INDIVIDUALISED MULTI-PRONGED and narratives that unfairly stereotype our patients with
APPROACH TO TREAT OBESITY obesity as unmotivated and lazy is a form of addressing
the obesity stigma and helping our patients overcome this
It is now known that the simple calculations underlying discrimination. Educating patients and their families on the
the traditional adage of “eat less, exercise more” are fatally nature of obesity as a disease will also help to fight weight
flawed.30 Aiming for a 500 kcal deficit (energy expenditure bias and stigma. Compositely, such measures can help PwO
more than energy intake) per day, cumulating to 3,500 obtain the quality healthcare they need.4,27
kcal per week (equivalent to ~0.5 kg of fat) will not result

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UNDERSTANDING OBESITY: HOW AND WHY?

Lastly, obesity prevention remains key to reducing the 5. Schwartz MW, Seeley RJ, Zeltser LM, Drewnowski A, Ravussin E,
burden of disease associated with obesity as a population Redman LM, et al. Obesity Pathogenesis: An Endocrine Society
Scientific Statement. Endocr Rev. 2017 Aug 1;38(4):267-296. doi:
moving forward.31 Primary care practitioners are often the 10.1210/er.2017-00111. PMID: 28898979; PMCID: PMC5546881.
first point of patient contact. Initiating the conversation in 6. Yu YH, Vasselli JR, Zhang Y, Mechanick JI, Korner J, Peterli R.
obesity with patients and addressing childhood obesity are Metabolic vs. hedonic obesity: a conceptual distinction and its
important roles primary care practitioners play in tackling clinical implications. Obes Rev. 2015 Mar;16(3):234-47. doi:
10.1111/obr.12246. Epub 2015 Jan 14. PMID: 25588316; PMCID:
the obesity epidemic. With obesity being prevalent in PMC5053237.
women in their reproductive years, the potential impact of 7. Morton GJ, Blevins JE, Williams DL, Niswender KD, Gelling
maternal obesity on the adiposity and metabolic health of RW, Rhodes CJ, et al. Leptin action in the forebrain regulates
future generations may be colossal and under-addressed. the hindbrain response to satiety signals. J Clin Invest. 2005
Mar;115(3):703-10. doi: 10.1172/JCI22081. PMID: 15711637;
While major public health measures to drastically reduce PMCID: PMC548313.
maternal obesity for a downstream impact seem unlikely at 8. Sumithran P, Proietto J.The defence of body weight: a physiological
the present moment, HCPs can play an important role in basis for weight regain after weight loss. Clin Sci (Lond). 2013
educating women in their reproductive years to maintain Feb;124(4):231-41. doi: 10.1042/CS20120223. PMID: 23126426.
9. Maclean PS, Bergouignan A, Cornier MA, Jackman MR. Biology’s
a healthy weight to improve pregnancy outcomes and
response to dieting: the impetus for weight regain. Am J Physiol
potentially the health of future generations.15 Regul Integr Comp Physiol. 2011 Sep;301(3):R581-600. doi:
10.1152/ajpregu.00755.2010. Epub 2011 Jun 15. PMID: 21677272;
PMCID: PMC3174765.
CONCLUSION
10. Farr OM, Li CR, Mantzoros CS. Central nervous system regulation
of eating: Insights from human brain imaging. Metabolism. 2016
Obesity is now recognised as a disease and has been described May;65(5):699-713. doi: 10.1016/j.metabol.2016.02.002. Epub
as a complex, chronic medical condition with a major 2016 Feb 6. PMID: 27085777; PMCID: PMC4834455.
negative impact on human health.27 Many associations and 11. Heymsfield SB, Wadden TA. Mechanisms, Pathophysiology, and
organisations, including the World Health Organisation Management of Obesity. N Engl J Med. 2017 Jan 19;376(3):254-
266. doi: 10.1056/NEJMra1514009. PMID: 28099824.
(WHO), have now declared obesity as a disease, and this is
12. Tam V,Turcotte M, Meyre D. Established and emerging strategies to
an important first step to tackling the problem of obesity. crack the genetic code of obesity. Obes Rev. 2019 Feb;20(2):212-
Understanding the biology of weight regulation and the 240. doi: 10.1111/obr.12770. Epub 2018 Oct 23. PMID: 30353704.
appreciation of the complex and multifactorial nature 13. Yengo L, Sidorenko J, Kemper KE, Zheng Z, Wood AR, Weedon
of how this regulation can go wrong resulting in obesity MN, et al. Meta-analysis of genome-wide association studies for
height and body mass index in -700000 individuals of European
would indicate that there is no one-size-fits-all intervention ancestry. Hum Mol Genet. 2018 Oct 15;27(20):3641-3649. doi:
or solution31 and would necessitate a multi-level and 10.1093/hmg/ddy271. PMID: 30124842; PMCID: PMC6488973.
individualised multi-pronged approach to treating obesity 14. Singh RK, Kumar P, Mahalingam K. Molecular genetics of human
and its related conditions. Strategies for long-term weight obesity: A comprehensive review. C R Biol. 2017 Feb;340(2):87-
108. doi: 10.1016/j.crvi.2016.11.007. Epub 2017 Jan 13. PMID:
maintenance, chronic follow-up with monitoring of weight 28089486.
regain and obesity-related diseases, and addressing the 15. Godfrey KM, Reynolds RM, Prescott SL, Nyirenda M, Jaddoe VW,
stigma and bias that PwO face are pertinent for successful Eriksson JG, et al. Influence of maternal obesity on the long-term
obesity management. Primary care practitioners play a health of offspring. Lancet Diabetes Endocrinol. 2017 Jan;5(1):53-
64. doi: 10.1016/S2213-8587(16)30107-3. Epub 2016 Oct 12.
pivotal role in initiating the conversation in obesity and PMID: 27743978; PMCID: PMC5245733.
addressing obesity prevention. 16. Lin X, Lim IY, Wu Y, Teh AL, Chen L, Aris IM, et al. Developmental
pathways to adiposity begin before birth and are influenced by
genotype, prenatal environment and epigenome. BMC Med. 2017
REFERENCES
Mar 7;15(1):50. doi: 10.1186/s12916-017-0800-1. PMID: 28264723;
1. GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, PMCID: PMC5340003.
Reitsma MB, et al. Health Effects of Overweight and Obesity in 17. Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. Impact
195 Countries over 25 Years. N Engl J Med. 2017 Jul 6;377(1):13- of the gut microbiota on inflammation, obesity, and metabolic
27. doi: 10.1056/NEJMoa1614362. Epub 2017 Jun 12. PMID: disease. Genome Med. 2016 Apr 20;8(1):42. doi: 10.1186/s13073-
28604169; PMCID: PMC5477817. 016-0303-2. PMID: 27098727; PMCID: PMC4839080.
2. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult 18. Rial SA, Karelis AD, Bergeron KF, Mounier C. Gut Microbiota and
body-mass index in 200 countries from 1975 to 2014: a pooled Metabolic Health: The Potential Beneficial Effects of a Medium
analysis of 1698 population-based measurement studies with 19·2 Chain Triglyceride Diet in Obese Individuals. Nutrients. 2016 May
million participants. Lancet. 2016 Apr 2;387(10026):1377-1396. 12;8(5):281. doi: 10.3390/nu8050281. PMID: 27187452; PMCID:
doi: 10.1016/S0140-6736(16)30054-X. Erratum in: Lancet. 2016 PMC4882694.
May 14;387(10032):1998. PMID: 27115820. 19. Stephens RW, Arhire L, Covasa M. Gut Microbiota: From
3. Ministry of Health Singapore. Executive Summary on National Microorganisms to Metabolic Organ Influencing Obesity. Obesity
Population Health Survey 2016/17 [Internet]. Singapore: Ministry (Silver Spring). 2018 May;26(5):801-809. doi: 10.1002/oby.22179.
of Health [cited 2021 March 4]. Available from: https://www.moh. PMID: 29687647.
gov.sg/resources-statistics/reports/national-population-health- 20. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al.
survey-2016-17 Gut microbiota from twins discordant for obesity modulate
4. Rubino F, Puhl RM, Cummings DE, Eckel RH, Ryan DH, Mechanick metabolism in mice. Science. 2013 Sep 6;341(6150):1241214. doi:
JI, et al. Joint international consensus statement for ending stigma 10.1126/science.1241214. PMID: 24009397; PMCID: PMC3829625.
of obesity. Nat Med. 2020 Apr;26(4):485-497. doi: 10.1038/ 21. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et
s41591-020-0803-x. Epub 2020 Mar 4. PMID: 32127716; PMCID: al. Metabolic endotoxemia initiates obesity and insulin resistance.
PMC7154011. Diabetes. 2007 Jul;56(7):1761-72. doi: 10.2337/db06-1491. Epub
2007 Apr 24. PMID: 17456850.

T h e S i n g a p o r e F a m i l y P h y s i c i a n V o l 4 9(9) O c t – D e c 2 0 2 3 : 1 0
 UNDERSTANDING OBESITY: HOW AND WHY?

22. World Obesity Federation. ROOTS of Obesity Fact Sheet 28. Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL,
[Internet]. World Obesity [cited 2021 March 4]. Available from: Jastreboff AM, et al. AMERICAN ASSOCIATION OF CLINICAL
https://www.worldobesityday.org/assets/downloads/Roots_of_ ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF
Obesity.pdf ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE
23. González-Muniesa P, Mártinez-González MA, Hu FB, Després JP, GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH
Matsuzawa Y, Loos RJF, et al. Obesity. Nat Rev Dis Primers. 2017 OBESITY. Endocr Pract. 2016 Jul;22 Suppl 3:1-203. doi: 10.4158/
Jun 15;3:17034. doi: 10.1038/nrdp.2017.34. PMID: 28617414. EP161365.GL. Epub 2016 May 24. PMID: 27219496.
24. Cuthbertson DJ, Steele T, Wilding JP, Halford JC, Harrold JA, 29. Cefalu WT, Bray GA, Home PD, Garvey WT, Klein S, Pi-Sunyer FX,
Hamer M, et al. What have human experimental overfeeding et al. Advances in the Science, Treatment, and Prevention of the
studies taught us about adipose tissue expansion and susceptibility Disease of Obesity: Reflections From a Diabetes Care Editors’
to obesity and metabolic complications? Int J Obes (Lond). 2017 Expert Forum. Diabetes Care. 2015 Aug;38(8):1567-82. doi:
Jun;41(6):853-865. doi: 10.1038/ijo.2017.4. Epub 2017 Jan 12. 10.2337/dc15-1081. PMID: 26421334; PMCID: PMC4831905.
PMID: 28077863. 30. Hall KD, Kahan S. Maintenance of Lost Weight and Long-Term
25. Obesity: preventing and managing the global epidemic. Report Management of Obesity. Med Clin North Am. 2018 Jan;102(1):183-
of a WHO consultation. World Health Organ Tech Rep Ser. 197. doi: 10.1016/j.mcna.2017.08.012. PMID: 29156185; PMCID:
2000;894:i-xii, 1-253. PMID: 11234459. PMC5764193.
26. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono 31. Amarasinghe A, D’Souza G. Individual, social, economic, and
C, et al. Global, regional, and national prevalence of overweight environmental model: A paradigm shift for obesity prevention.
and obesity in children and adults during 1980-2013: a systematic International Scholarly Research Notices. 2012;2012.
analysis for the Global Burden of Disease Study 2013. Lancet. 2014 32. Bessesen DH, Van Gaal LF. Progress and challenges in anti-
Aug 30;384(9945):766-81. doi: 10.1016/S0140-6736(14)60460-8. obesity pharmacotherapy. Lancet Diabetes Endocrinol. 2018
Epub 2014 May 29. Erratum in: Lancet. 2014 Aug 30;384(9945):746. Mar;6(3):237-248. doi: 10.1016/S2213-8587(17)30236-X. Epub
PMID: 24880830; PMCID: PMC4624264. 2017 Sep 14. PMID: 28919062.
27. Upadhyay J, Farr O, Perakakis N, Ghaly W, Mantzoros C. Obesity 33. Kheniser K, Saxon DR, Kashyap SR. Long-term weight loss
as a Disease. Med Clin North Am. 2018 Jan;102(1):13-33. doi: strategies for obesity. J Clin Endocrinol Metab. 2021 Feb
10.1016/j.mcna.2017.08.004. Epub 2017 Oct 21. PMID: 29156181. 17:dgab091. doi: 10.1210/clinem/dgab091. Epub ahead of print.
PMID: 33595666.

LEARNING POINTS
• Obesity is now recognised as a chronic disease that is complex and of a multifactorial nature.
• Understanding the various roots in the individual will allow interventions to be tailored to address
these aetiologies and aggravating factors. There is no one-size-fits-all solution, and management
necessitates a multi-level and individualised multi-pronged approach to treating obesity and its
related conditions.
• Long-term follow-up is required for assessment of treatment, monitoring of weight regain and
obesity-related diseases. Alongside addressing the obesity stigma and bias, these practices are
pertinent in managing and preventing obesity and its related complications.

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