Inflammation and Obesity: A New and Novel Approach to Manage Obesity and its Consequences

Inflammation and Obesity: A New and Novel Approach to Manage Obesity and its Consequences is a comprehensive and up-to-date exploration of the correlation between obesity and inflammation. From the pathophysiology of obesity and inflammation, to the molecular mechanisms of obesity induced chronic inflammation, the book discusses how obesity and inflammation interact with other diseases. It highlights the hidden risk factors of obesity induced chronic inflammation, provides specific patient management guidelines regarding the higher inflammatory response in patients, and concludes with new therapeutic strategies to address inflammation in obese patients.

• Identifies the hidden physiological changes that accompany obesity, while also highlighting the challenge of managing obesity with a higher inflammatory response
• Discusses major hidden health risks of inflammation that accompany obesity, as well as management guidelines for obese patients
• Links the pathophysiology of inflammation and obesity to the therapeutic strategies that minimizes risk factors, thus opening new areas of research

• Language: English
• Publisher: Academic Press
• Release date: Sep 24, 2022
• ISBN: 9780323909617

Book preview

Chapter 1: Introduction to obesity and inflammation

Raman Mehrzad    Division of Plastic and Reconstructive Surgery, Rhode Island Hospital, The Warren Alpert School of Brown University, Providence, RI, United States

Key words

Obesity; Inflammation; Pandemic; Global

Obesity is a global, complex, multifactorial, and generally preventable disease. The global prevalence of obesity has doubled in the past 40 years regardless of sex, age, ethnicity, or socioeconomic status. Today, more than one-third of the world’s population is classified as obese or overweight. If this trend continues, researchers estimate that by 2030, this number will hit over 50%. Based on this, there is continuous research being pursued each year with new scientific articles, evidence, guidelines, and management coming out on this topic.

Inflammation is a biologic sequence of events evolutionary designed to maintain tissue and organ homeostasis. Different mediators and expression of receptors are timely released to restore tissues to their original condition [1]. Additionally, inflammation is a protective tissue response to injury or destruction of tissues that serves to destroy or dilute both the injurious agent and the injured tissues [2].

Two main types of inflammation exist: acute and chronic inflammation. Acute inflammation lasts for a brief period and is characterized by edema and migration of leukocytes. Chronic inflammation lasts for a long time and is characterized by the presence of lymphocytes and macrophages and the proliferation of blood vessels and connective tissue [3].

Obesity, a feature of metabolic syndrome, is associated with chronic with secretion of inflammatory adipokines usually from adipose tissue, such as leptin, interleukin (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP), and resistin [4,5]. In recent years, it has been proven that obesity is associated with a low-grade inflammatory state and process with increase in circulating levels of the above proinflammatory cytokines in healthy obese subjects [6]. The same phenomenon is also seen in obese children who have higher CRP levels than normal-weight children [6]. Weight loss, mainly through diet, has been demonstrated in some studies to be associated with reduction in circulating levels of IL-6, TNF-alpha, CRP, and other markers of inflammation, independently of age, sex, and BMI. Similarly, subjects who lose weight after gastric bypass show decrease of CRP and IL-6 levels [6]. Sustained inflammation is considered a strong risk factor for developing many diseases including metabolic syndrome, cancer, diabetes, and cardiovascular disease.

Consequently, obesity and metabolic disorder are accompanied by chronic low-grade inflammation, which could have fundamentally consequences to our health. Thus, this foundation has changed our view of the underlying causes and progression of obesity. Inflammatory cascades are activated early in adipose expansion and during obesity, lastingly skewing the immune system to a proinflammatory state. Moreover, numerous studies have demonstrated that one of the major consequences of obesity is not only the initiation of inflammation, but its relevant role in causing insulin resistance, impaired insulin secretion, and disruption of other aspects of energy homeostasis [5].

Importantly, obesity-induced inflammation is different from other inflammatory types in that it involves stimulatory activation of the innate immune system that impacts metabolic homeostasis, that in many cases last for many years, if not a lifetime. Obesity-related inflammation also results in inadequate responses such as necrosis and fibrosis that can lead to significant tissue damage. Furthermore, this type of inflammation is unique in that it encompasses multiple organs, including the skeletal muscle, brain, adipose, pancreas, liver, and heart [5].

Therefore, outlining the reciprocal influence of obesity and inflammation is of crucial importance to not only find new therapeutic strategies to fight this pandemic but also to manage its complications. With this foundation, this book gathered a group of experts that has provided reviews that dive deeply into the mechanisms and links between obesity and inflammation, and furthermore, its consequences within different organ systems and our biology.

References

[1] Romano M. Inflammation resolution: does the bone marrow have a say?. Am J Hematol. 2008;83(6):435–436.

[2] Feuerstein G.Z., Libby P., Mann D.L. Inflammation—a new frontier in cardiac disease and therapeutics. In: Feuerstein G.Z., Libby P., Mann D.L., eds. Inflammation and cardiac diseases. Birkhäuser Basel; 2003:1–5.

[3] Seki H., Tani Y., Arita M. Omega-3 PUFA derived anti-inflammatory lipid mediator resolvin E1. Prostaglandins Other Lipid Mediat. 2009;89(3–4):126–130.

[4] Stępień M., Stępień A., Wlazeł R.N., Paradowski M., Banach M., Rysz J. Obesity indices and inflammatory markers in obese non-diabetic normo- and hypertensive patients: a comparative pilot study. J Lipids Health Dis. 2014;13:29.

[5] Ellulu M.S., Patimah I., Khaza'ai H., Rahmat A., Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017. ;13(4):851–863. doi:10.5114/aoms.2016.58928. Epub 2016 Mar 31 28721154 PMC5507106.

[6] Rodríguez-Hernández H., Simental-Mendía L.E., Rodríguez-Ramírez G., Reyes-Romero M.A. Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. Int J Endocrinol. 2013. ;2013:678159. doi:10.1155/2013/678159. Epub 2013 Apr 17 23690772 PMC3652163.

Chapter 2: The obesity pandemic: How we are failing our patients

Ronald Tyszkowskia; Raman Mehrzadb    a Private Practice, Allied Health, Women and Infants Hospital, Providence, RI, United States

b Division of Plastic and Reconstructive Surgery, Rhode Island Hospital, The Warren Alpert School of Brown University, Providence, RI, United States

Abstract

The meteoric rise in obesity rates worldwide is nothing short of astonishing. Without any respect for clinical guidelines, nutritional strategies, fad diets, dubious pharmacological agents, and surgical intervention, obesity has set its sights on claiming no less than 50% of the world’s population by 2050. Where will it end? How will we stop this pathologic behemoth? Only time will tell. But it serves us well to see where we are at, how we got here, and where we are heading if things don’t change.

Keywords

Obesity; Pandemic; BMI; Type 2 diabetes; Cancer; Bias

Obesity as a disease

Obesity is defined by the World Health Organization (WHO) as excessive fat accumulation that might impair health and is diagnosed at a BMI of ≥  30 kg/m²[1]. The 2017 Global Nutrition Reports showed that 2 billion adults and 40 million children are overweight, worldwide [2].

The US Department of Health and Human Services called obesity "the single greatest threat to public health for this century [3]."It is universally recognized as a significant health hazard and is associated with a decreased life expectancy of from 5 to 20 years, depending on the severity of the condition and the presence of associated comorbidities including cancer, cardiovascular disease, diabetes mellitus [4], and poor mental health; all of which have a negative effect on quality of life, work productivity, and healthcare costs. In 2005, the Center for Disease Control estimated that 365,000 people die annually from obesity [5]. And some studies predict that life expectancy will level off or decline by 2050 due to childhood obesity [6]. In the United States, it has been estimated that the health cost incurred by a single obese individual was $1901 per year in 2014, extrapolating to $149.4 billion at the national level [7]. In England, the total direct and indirect costs attributable to overweight and obese individuals were equivalent to 0.47%–0.61% of the GDP [8].

This worldwide epidemic of obesity is not a new phenomenon. The International Obesity Task Force was formed in the mid-1990s with the aim of expanding awareness of this growing problem. The WHO in 1997 convened the Expert Technical Consultation on Obesity and published its findings in 2000. Obesity was officially classified as a disease in 1990 (ICD-10 E66.0) [9]. In 2013, the American Medical Association recognized obesity as a disease, of growing scientific, social, and political interest [10]. It stated that recognizing obesity as a disease will help change the way the medical community tackles this complex issue.

Classifying obesity as a disease also produced a significant amount of criticism as well. It has historically been a highly stigmatized condition that has long been generally regarded by the public as a reversible consequence of personal choices [3]. Michael Tanner wrote in The National Review in 2015 that this move was a symptom of another disease, the abdication of personal responsibility and an invitation to government meddling. [11]. Many other organizations have also adopted this terminology (Fig. 1)

Fig. 1

Fig. 1 Associations that have declared obesity as a disease [13].

Randolph Nesse wrote about disease classification: Our social definition of disease will remain contentious, however, because values vary, and because the label ‘disease’ changes the moral status of people with various conditions, and their rights to medical and social resources. [12].

Epidemiology

Despite the universally accepted premise that it needs to be addressed as an urgent public health issue, incidence continues to rise in the United States and globally. No country or subpopulation within a country has achieved a decrease in obesity, representing one of the biggest population health failures of our time [14]. Trends in obesity, which had leveled off briefly in 2009–12, project to 50% of adults by 2030. In the United States, rates of obesity will surpass 50% by 2030 in 29 states and not below 35% in any state [15]. Additionally, severe obesity (BMI ≥  35) will affect one in four and become the most common BMI category in women, black non-Hispanic adults, and low-income adults.

Extrapolating trends out to 2050 paints an even worse picture. Men in age group 31–40 (Fig. 2) project to an almost 70% rate of obesity by 2050. Interestingly, women also project to a slightly less percentage of obesity of 60%, but at a later age range of 61–70, possibly related to the hormonal variability of menopause (Fig. 3).

Fig. 3

Fig. 2 Estimated percentage of males who are obese at 2007 and 2050 [9] .

Fig. 4

Fig. 3 Estimated percentage of women who are obese at 2007 and 2050 [9] .

Global impact of obesity

Obesity worldwide

•In a majority of European countries, the prevalence of obesity has increased from 10% to 40% in the last 10 years [9].

•In England, prevalence has tripled in the last 10 years [9].

•In 2009, one in five Americans were morbidly obese [9]

•As the Western diet combined with modern food preparation techniques moves across the world, projected rates of obesity in Africa increase by 162%, in India by 150%, and in China by 104% by 2030 (Fig. 4) [16]. Fig. 5 shows the expected increase in rate of obesity as broken down by ethnic group.

Fig. 4 The percentage obese in 2000 vs 2030, with the percent increase. [16] .

Fig. 5 Predicted percentage of male population obese at 2006 and 2050 by ethnic group [9] .

Impact of increased incidence of obesity

In Fig. 6, the effect of obesity on quality of life is demonstrated over a 20-year period. Unhealthy obese patients show the greatest decrease in physical function and overall body pain.

Fig. 8

Fig. 6 Decline in physical function (A) and worsening of bodily pain (B) over two decades by initial metabolic and obesity status. Models include adjustment for 1991/1994 values of age, sex, ethnicity, occupational position, moderate-to-vigorous physical activity, smoking, alcohol, and fruit and vegetable consumption. [17].

This increase will inevitably coincide with an increase in medical costs and percentage of GDP directed to obesity-related costs.

Origins of the obesity epidemic

Studies into the origins of obesity can guide the clinician to target those with higher risk factors inherently and modify behavior strategically. Multiple literature reviews list those factors, which are summarized below.

Sociodemographic factors associated with obesity [18]

•Older age

•Married

•Low wealth index

•Urban residency

•Female

•Easy accessibility of nutrient dense foods secondary to a free trade policy

•Rural to urban migration

•Higher education levels

•Pregnancy

Behavioral factors associated with obesity

•Consuming energy-dense food, such as confectionaries, sugars, soft drinks, fats, and alcohol

•Consuming pastry foods

•Consuming ultraprocessed food (refined carbohydrates)

•Excess alcohol consumption

•Monotonous diet or poor diet quality

•Evening snack induces obesity

•Irregular physical exercise or physical inactiveness

•Watching television or prolonged screen time

•Short sleep duration or shift work

•Stress

•Obesogenic environment (urbanization and industrialization)

•Smoking

•Frequent use of a taxi for transportation

The Quebec Family Study, an observational study published in 2014, looked at the contribution of familial resemblance and genetic effects on body fatness and behaviors related to energy balance [19]. Fig. 7 shows the common risk factors, high-fat diet, and lack of physical activity. But it also shows newer emerging risk factors of:

•low calcium intake,

•binge eating,

•lack of sleep,

•various combinations of the three.

Fig. 9

Fig. 7 Common and emerging risk factors for obesity from the 2014 Quebec Study [19] .

Since obesity has been so resistant to treatment, in that rates continue to rise, these risk factors can help us to identify vulnerable populations and dangerous behavior so that interventions can happen earlier before the disease sets in.

Obesity and disease

Obesity and its myriad of physiologic sequelae are a significant health issue. However, the problem does not stop there. It predisposes the affected individual to increased risk of a multitude of chronic, life-threatening illnesses. Type 2 diabetes and cancer are two disease states inexorably linked to obesity (Fig. 8).

Fig. 10

Fig. 8 The many comorbidities of obesity [20].

Type 2 diabetes

In total, 90% of type 2 diabetes is attributable to obesity, and obesity-related metabolic syndrome causes impaired glucose tolerance in 197 million people worldwide. The prevalence of type 2 diabetes is expected to increase to 366 million by 2033, with the most prominent increase in developing countries [16].

Type 2 diabetes mellitus (T2D) is one of the defining medical challenges of the 21st century [21]. Overconsumption of relatively inexpensive, calorically dense, inadequately satiating, highly palatable food in industrialized nations has led to unprecedented increases in obesity [21]. In the United States, the combined prevalence of diabetes and prediabetes is over 50% [22]. Although only a subset of obese people develops T2D, obesity is a major risk factor for T2D, and rates of T2D prevalence have paralleled those of obesity [23].

Obesity and cancer

Pan et al. [24] found that:

•Obese and overweight people had respective risks of 34% and 9% higher for all 19 cancers combined compared with subjects with a body mass index of less than 25 kg/m²[24].

•Obese people had an increased risk of non-Hodgkin’s lymphoma, leukemia, multiple myeloma, and cancers of the kidney, colon, rectum, breast (in postmenopausal women), ovary, pancreas, and prostate [24].

•Another study showed that in men, a 5 kg/m² increase in BMI was strongly associated with esophageal adenocarcinoma and with thyroid, colon, and renal cancers. In women, strong associations between a 5 kg/m² increase in BMI and esophageal adenocarcinoma and with endometrial, gallbladder, and renal cancers were noted [25].

•Among postmenopausal women in the United Kingdom, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese [26].

These observations provide strong evidence for the positive association between obesity and overall cancer and some site-specific cancers. If the association were causal, overweight and obesity would be responsible for 7.7% of overall cancer incidence [24].

Failures in management of obesity

Poor training

Current management strategies and/or practice prevention steps are proving to be ineffective. There has been very little implementation of comprehensive, policy-based approaches [27]. Additionally, health professionals are often poorly prepared to treat obesity [28]. They receive little nutritional training and are not prepared to assess diet and/or provide nutritional counseling [29].

A study that surveyed physicians at the University of Michigan [30] showed that few were confident in their ability to change patient behaviors. Only 10.8% of trainees and 17.3% of attending physicians reported that high self-efficacy for changing patients’ diet-related behaviors with a similar pattern was observed related to self-efficacy to change patients’ behaviors related to exercise.

Physicians were also asked about training in counseling by asking to agree with the following statement: I received adequate training in lifestyle counseling patients. Only 12.7% of trainees and 23.5% for attending physicians agreed that they had received adequate training in counseling on diet. Only 13.7% of trainees and 17.3% of attending physicians agreed that they had received adequate training in counseling on exercise.

Practitioner bias

Obesity also affects provider’s attitudes toward their patients. Physicians are reported to be one of the most frequent sources of weight bias [31]. In fact, research has shown that negative stereotypes and stigma exist within a diverse group of healthcare providers including physicians, nurses, dieticians, and psychologists [32]. In 2010, the British Public Health Minister advocated for calling patients fat because obese did not have the necessary emotional impact. Her reasoning was that patients would be less worried about their weight if they were simply referred to as obese.

Weight stigmatization like this can lead to heightened risk of psychological distress, maladaptive eating behaviors, exercise avoidance, reduced healthcare utilization, and poorer outcomes in weight loss treatment [32]. So regardless of the effectiveness of any diet, exercise, or pharmaceutical approach, these biases can negate them.

Primary care providers engage in less patient-centered communication with patients they believe are not likely to be adherent [33]. A common explicitly endorsed provider stereotype about patients with obesity is that they are less likely to be adherent to treatment or self-care recommendations, are lazy, undisciplined, and weak-willed. Primary care providers have reported less respect for patients with obesity compared with those without [34,35], and low respect has been shown to predict less positive affective communication and information giving [36]. They may also allocate time differently, spending less time educating obese patients about their health [37].

Finally, physicians may fail to refer for diagnostic testing or to consider treatment options beyond advising the patient to lose weight [38], jumping to the conclusion that obesity is the root cause of the patient’s presenting symptoms.

Primary care nursing also falls victim to preexisting beliefs or prejudice toward obese patients. Brown showed that of 546 UK nurses surveyed in 2006 that only 8.2% believed that obese patients were motivated to change, while agreeing with statements that working with population was rewarding and to feeling empathy toward obese patients [39]. The emotional conflict demonstrated by this survey crystalizes the challenges practitioners face as they attempt to manage these patients despite the harsh societal prejudgments ingrained in our collective psyche.

A moving article, Voices of Patients with Obesity articulately states what patients are looking for from their doctors. Thirty years after classifying obesity as a disease, we are still failing to provide even basic care and understanding. As one of the authors of this articles pleads, I know you are behind, that you are dealing with patients with cancer and heart disease, rare diseases, and sinus infections. I know you need more than my allotted 15 minutes. But I am here today, and if you don’t have time to help me with a plan, who does? [40].

Practitioners have to be the bulwark against the seemingly unstoppable tide of obesity. It starts with us.

References

[1] Fontaine K.R. Years of life lost due to obesity. JAMA. 2003;289(2):187–193.

[2] Hawkes C., Fanzo J. Nourishing the SDGs: global nutrition report 2017. Bristol: Development Initiatives Poverty Research Ltd; 2017.

[3] United States. Dietary Guidelines Advisory Committee. Dietary guidelines for Americans, 2010. No. 232. US Department of Health and Human Services, US Department of Agriculture; 2010.

[4] Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288–298.

[5] Couzin J. A heavyweight battle over CDC's obesity forecasts. Science. 2005;770–771.

[6] Mann C.C. Provocative study says obesity may reduce US life expectancy: the rising incidence of obesity, especially among children and teenagers, is leading to a variety of diseases that could depress average life span. Science. 2005;307(5716):1716–1718.

[7] Kim D.D., Basu A. Estimating the medical care costs of obesity in the United States: systematic review, meta-analysis, and empirical analysis. Value Health. 2016;19(5):602–613.

[8] von Lengerke T., Krauth C. Economic costs of adult obesity: a review of recent European studies with a focus on subgroup-specific costs. Maturitas. 2011;69(3):220–229.

[9] Agha M., Agha R. The rising prevalence of obesity: part a: impact on public health. Int J Surg Oncol. 2017;2(7):e17.

[10] De Lorenzo A. Obesity: a preventable, treatable, but relapsing disease. Nutrition. 2020;71:110615.

[11] Tanner M. Obesity is not a disease. Natl Rev. 2013 Online.

[12] Nesse R.M. On the difficulty of defining disease: a Darwinian perspective. Med Health Care Philos. 2001;4(1):37–46.

[13] Kahan S., Zvenyach T. Obesity as a disease: current policies and implications for the future. Curr Obes Rep.