The Link Between Obesity and Cancer

The Link between Obesity and Cancer provides a comprehensive review on the relationship between obesity and cancer, presenting global perspectives on obesity and cancer incidence that are followed by in-depth discussions on cancers for which we have new evidence of a causal relationship with obesity. Readers will gain fundamental knowledge on which cancer types are related to obesity. In addition, this updated resource provides significant knowledge for clinicians on when to act, along with specific management guidelines for patients, as well as how to understand potential risk factors and how to directly or indirectly minimize these risks.

The book also provides never-before-published scientific data for any researcher in the field, identifying molecular mechanisms and links behind the development of malignancy and promoting research in new and effective target pathways in developing therapeutic strategies.

• Provides essential knowledge on how to understand the link between obesity and cancer and why and how this occurs
• Presents a significant knowledge base for clinicians on when to act, along with patient management guidelines for patients with obesity and potential risk factors
• Contains new scientific data and findings for researchers that identify the molecular mechanisms and links behind the development of malignancy

• Language: English
• Publisher: Academic Press
• Release date: Sep 22, 2022
• ISBN: 9780323909662

Book preview

1: Introduction: The obesity pandemic

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

Keywords

Obesity pandemic; Cancer and obesity

1: Overview and definition of obesity

Obesity is a global, complex, multi-factorial, and generally preventable disease [1]. The global prevalence of obesity has doubled in past 40 years regardless of sex, age, ethnicity, or socioeconomic status. Today, more than one-third of the world's population are classified as obese or overweight [2]. If this trend continues, researchers estimate that by 2030, this number will hit over 50% [3].

Obesity is typically defined as excess body weight for height. Today, due to its simplicity and low cost, body mass index (BMI), defined as the weight in kilograms divided by the height in meters squared (kg/m²), is the most commonly used measure of obesity. The National Institutes of health (NIH) and World Health Organization (WHO) define overweight as having a BMI between 25.0 and 29.9 kg/m² and obesity as having a BMI greater than 30.0 kg/m²[4,5].

For children, criteria for overweight are based on the 2000 US Centers for Disease Control and Prevention (CDC) BMI-for-age growth charts in the United States. Here, at or above the age-specific 95% BMI percentile is defined as overweight. Those at risk for overweight are defined as having a BMI between 85th and 95th percentiles of the BMI-for-age growth chart [6].

Recently, there has been more evidence suggesting that abdominal fat rather than total body fat is an independent risk factor of cancer-related and cardiovascular outcomes. It has been suggested that the visceral and metabolically active fat surrounding the organs causes metabolic dysregulation, which in turn predisposes to disease. This is also known as the metabolic syndrome, which per international guidelines is a collection of dysmetabolic conditions that puts individuals in increased risk for cardiovascular disorders [7]. Nowadays, it is therefore common practice to measure waist and hip circumference as well as the waist-to-hip ratio. It should be noted that the waist circumference that is defined to increase the risk for disease is different depending on race. For instance, a waist circumference in European men > 94 and > 80 cm in European women are linked to higher cardiovascular risk, although in the Asian population, the cut off is 90 vs 80 cm in men and women, respectively [8].

2: Brief prevalence of obesity

Recent epidemiology studies have estimated that a total of 1.9 billion people worldwide were obese or overweight in 2015. This represents 39% of the world's population [3]. The prevalence is somewhat lower in women than men among ages between 20 and 44 years; however, from 45 to 49 years, the trend reverses between the genders. Generally, obesity rates start to increase from 20 years of age and peak between 50 and 65 years with a slight decline subsequently. An increase of nearly 50% has been seen in age-standardized prevalence in obesity over the past three and a half decades from 26.5% in 1980 to 39% in 2015, while the prevalence increased by 7% to 12.5% during the same time frame, accounting for an almost 80% increase [3]. Women had a greater prevalence rate of overweight and obesity than men in this period. The prevalence of obesity is in large uniform globally, although there are some variability between regions and countries [3].

3: Epidemiological studies

The American Medical Association (AMA) recognizes obesity as a disease. Whether it is a condition that leads to disease or a disease itself, there is a strong worldwide consensus that obesity is pandemic and needs to be treated and more importantly prevented (especially in children) owing to its significant comorbidities, mortality, and costs.

The purpose of epidemiological studies is to capture a baseline of where we stand in the issue of obesity and identify the determinants and consequences to later find strategies for prevention and interventions. Epidemiology of obesity covers different research activities with the aim to study and monitor risk factors, consequences, population trends, and to conduct studies on how to prevent and treat obesity [9].

Epidemiology studies in general are crucial to identify trends and patterns and later develop guidelines and recommendation for the population. Many of the current strategies have emerged from data of epidemiological studies [9]. For instance, the knowledge of the consequences of obesity has made us be aware that this is health danger to our population and thereby, we now measure BMI, waist circumference, track progress of weight gain and loss, etc. It has also resulted in emphasizing treatment options for patients who are at risk of obesity or are in the class of different stages of obesity. Therefore continuous reports of these data are important to be able to refine our recommendations for patients and decrease mortality and morbidity. Moreover, studies on epidemiology encourage other research areas to actively analyze various molecular mechanisms, which further can identify targets for pharmaceutical approaches. A couple of examples of this are medications such as Orlistat (Xenical) and Lorcaserin (Belviq). These drugs target enzymes, receptors, and hormones that have been found to play a role in fat absorption and appetite [10,11].

4: Health consequences of obesity

Obesity has many serious health consequences. It affects nearly all physiological functions in the body adversely and increases the risks of cardiovascular diseases, hypertension, hyperlipidemia, chronic kidney disease, diabetes, cancers, musculoskeletal disorders, and poor mental health, just to name a few [12–16]. This area of research has grown significantly over the past few years, partly because obesity is an epidemic and partly because we now also have better quantitative methods in the field with the availability of body size or adiposity measurements in all epidemiological or clinical studies. Although these studies continue to improve our understanding of the disease and its healthcare consequences, there are still many questions that remain between the relationship of adiposity and how it brings different disease states and the impact of obesity on mortality [9].

5: Brief etiology of obesity

The etiology of obesity is molecularly simple to understand. Higher calorie intake than calorie expenditure results in a net positive calorie excess that in turn causes weight gain. Although this is simple mathematics, the actual regulation of body weight and fat is very complex and is a complicated interrelation of behavioral, genetic, endocrine, psychosocial, and environmental factors. Although we understand many of the causes of obesity, understanding these interrelations and other contributing factors are still elucidated. One of the issues with studies that determine predictors of obesity is that it has many methodological problems such as reverse causation, confounding, and imprecise diet and physical exercise. In general, calorie intake and expenditure are many times subjective and not always easy to measure properly by patients or clinicians. Furthermore, obesity could at times bring certain behaviors and vice versa, and therefore reverse causation bias is a common encountered issue. These problems result in limitations when attempting to design study methods and making accurate conclusions.

6: Cost of obesity

The healthcare costs of obesity in the United States are enormous. The cost of obesity is in the hundreds of billions range in the United States only per year and a significant portion of the gross domestic product in Europe when accounting for both direct and indirect costs. More detailed report of the economic impact is given in Chapter 5[17,18].

7: Goal of obesity research

The major objective of research in obesity is to prevent it from happening and to treat those who are affected by it. Many studies on different dietary strategies and lifestyle modifications have been done at different levels: individual, community, school, and society levels. While we have many different tactics on prevention and treatment of obesity, sufficient and sustainable interventions are yet to be found. This is true since regardless of the numerous strategies, the obesity trend is still growing which proves that the problem is very complex [9].

8: Obesity and cancer

There is consistent evidence that higher amounts of body fat are associated with increased risks of a number of cancers. A population-based study using BMI and cancer incidence data from the GLOBOCAN project estimated that, in 2012 in the United States, about 28,000 new cases of cancer in men (3.5%) and 72,000 in women (9.5%) were due to overweight or obesity [19]. The percentage of cases attributed to overweight or obesity varied widely for different cancer types but was as high as 54% for gallbladder cancer in women and 44% for esophageal adenocarcinoma in men.

A 2016 study summarizing worldwide estimates of the fractions of different cancers attributable to overweight/obesity reported that, compared with other countries, the United States had the highest fractions attributable to overweight/obesity for colorectal cancer, pancreatic cancer, and postmenopausal breast cancer [20].

There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancers [21].

There are a number of mechanisms that might explain the relationship between obesity and cancer, including pathways related to inflammation, insulin resistance, and sex hormones. There is limited evidence suggesting that obesity may also be associated with poor prognosis among patients with colorectal cancer, breast cancer, endometrial cancer, ovarian cancer, and pancreatic cancer. With this foundation, these findings support efforts to assist patients to prevent weight gain on an individual level as well as on a population level. Whether and to what extent overweight or obese cancer patients benefit from weight loss strategies is unclear and needs to be addressed in future studies. This book therefore focuses on providing previous and new scientific-based knowledge about obesity and its relationship with different cancer types [22].

References

[1] American Medical Association. AMA adopts new policies on second day of voting at annual meeting [Internet]. [cited 2014 Apr 7]. Available from: http://www.ama-assn.org/ama/pub/news/news/2013/2013-06-18-new-ama-policies-annual-meeting.page. 2013.

[2] Global Burden of Disease Study 2015. Global burden of disease study 2015 (GBD 2015) obesity and overweight prevalence 1980–2015. Seattle, United States: Institute for Health Metrics and Evaluation (IHME); 2017.

[3] Chooi Y.C., Ding C., Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10. doi:10.1016/j.metabol.2018.09.005 [Epub 2018 Sep 22].

[4] World Health Organization. Obesity. Available at http://www.who.int/topics/obesity/en. 2008.

[5] Kumanyika S.K., Obarzanek E., Stettler N., Bell R., Field A.E., Fortmann S.P., et al. Population-based prevention of obesity: the need for comprehensive promotion of healthful eating, physical activity, and energy balance: a scientific statement from American Heart Association Council on Epidemiology and Prevention, Interdisciplinary Committee for Prevention (formerly the expert panel on population and prevention science). Circulation. 2008;118(4):428–464. doi:10.1161/CIRCULATIONAHA.108.189702.

[6] US Centers for Disease control and Prevention. Overweight and obesity. Available at: http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm. 2008.

[7] Alberti K.G., Eckel R.H., Grundy S.M., Zimmet P.Z., Cleeman J.I., Donato K.A., Fruchart J.C., James W.P., Loria C.M., Smith Jr. S.C. International diabetes federation task force on epidemiology and prevention., Hational heart, lung, and blood institute., American Heart Association., world heart federation., international atherosclerosis society., International Association for the Study of obesity. Circulation. 2009;120(16):1640–1645.

[8] Alberti K.G., Zimmet P., Shaw J. IDF Epidemiology Task Force Consensus Group. Lancet. 2005;366(9491):1059–1062.

[9] Hu F.B. Obesity epidemiology. USA: Oxford University Press; Mar 21, 2008 Chapter 1: Introduction to Obesity epidemiology.

[10] Jain S.S., Ramanand S.J., Ramanand J.B., Akat P.B., Patwardhan M.H., Joshi S.R. Evaluation of efficacy and safety of orlistat in obese patients. Indian J Endocrinol Metab. 2011;15(2):99–104.

[11] Brashier D.B., Sharma A.K., Dahiya N., Singh S.K., Khadka A. Lorcaserin: a novel antiobesity drug. J Pharmacol Pharmacother. 2014;5(2):175–178.

[12] Singh G.M., Danaei G., Farzadfar F., et al. The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLoS One. 2013;8(7):e65174.

[13] Czernichow S., Kengne A.P., Stamatakis E., et al. Bodymass index, waist circumference and waist-hip ratio: which is the better discriminator of cardiovascular disease mortality risk?: evidence from an individual-participant meta-analysis of 82 864 participants from nine cohort studies. Obes Rev. 2011;12(9):680–687.

[14] Lauby-Secretan B., Scoccianti C., Loomis D., et al. Body fatness and cancer–viewpoint of the IARC working group. N Engl J Med. 2016;375(8):794–798.

[15] Anandacoomarasamy A., Caterson I., Sambrook P., et al. The impact of obesity on the musculoskeletal system. Int J Obes (Lond). 2008;32(2):211–222.

[16] Anstey K.J., Cherbuin N., Budge M., et al. Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev. 2011;12(5):e426–e437.

[17] 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.

[18] 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.

[19] Arnold M., Pandeya N., Byrnes G., et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol. 2015;16(1):36–46.

[20] Whiteman D.C., Wilson L.F. The fractions of cancer attributable to modifiable factors: a global review. Cancer Epidemiol. 2016;44:203–221.

[21] Avgerinos K.I., Spyrou N., Mantzoros C.S., Dalamaga M. Obesity and cancer risk: emerging biological mechanisms and perspectives. Metabolism. 2019;92:121–135. doi:10.1016/j.metabol.2018.11.001 Epub 2018 Nov 13. PMID: 30445141.

[22] Pischon T., Nimptsch K. Obesity and risk of Cancer: an introductory overview. Recent Results Cancer Res. 2016. ;208:1–15. doi:10.1007/978-3-319-42542-9_1. 27909899.

2: Physiology of obesity and metabolism

Jacqueline J. Chua; Raman Mehrzadb    a The Ohio State University College of Medicine, Columbus, OH, United States

b Division of Plastic Surgery, Brown University, Providence, RI, United States

Abstract

In order to understand the links between obesity and cancer, we must first understand how obesity develops and the systemic impact it has on the human body. To do so, we must recognize that adipose tissue has functions beyond fat storage. It is a living organ that communicates with the rest of the body to maintain homeostasis, and it becomes dysfunctional when it undergoes stress, which occurs in conditions like obesity. This chapter will provide an overview of metabolism and the functions of adipose tissue in non-obese individuals and then describe how these processes become deranged in the obese state, leading to systemic metabolic dysfunction and metabolic syndrome.

Keywords

Metabolism; Energy balance; Glucose; Insulin; Obesity

1: Metabolism and energy balance

Metabolism describes the processes through which living organisms convert food and nutrients into the energy required to support the functions necessary for growth and survival. In humans, energy expended can be grouped into three main categories: activity-induced energy expenditure, thermic effect of food, and resting energy expenditure [1]. Activity-induced energy expenditure is primarily composed of the energy used for physical activity as well as thermogenesis (e.g., shivering), while thermic effect of food is the energy that must be used to digest food. Resting energy expenditure, also called basal metabolic rate, is the energy used at rest to maintain functions necessary for growth and survival; two-thirds of all energy expended are used for basal metabolism. Resting energy expenditure varies from individual to individual, with most of the variation explained by body mass, especially fat-free mass [2,3]. As a result, men and younger individuals, who generally have higher fat-free mass, tend to have higher basal metabolic rates than women and older individuals [4].

When the same amount of energy is taken in as is expended, an organism is at energy balance [5]. However, when energy is in excess, such as when an individual overeats, that unexpended energy is then converted mostly into fat and stored for future use. Conversely, when energy is deficient, the fat can be metabolized and used. Based on this simple framework of energy balance as energy intake vs energy expenditure, humans should continually experience huge fluctuations in weight almost on a daily basis. Instead, body weight remains relatively stable with weight gains and losses usually occurring gradually over time, and this is because the body tightly regulates energy balance through controlling its components. Contributors to energy intake, expenditure, and storage are all modulated by a myriad of physiologic processes. As will be explained later on in this chapter, these processes are often dysfunctional in the obese individual, leading to metabolic consequences.

2: Regulation of energy balance

All aspects of energy balance in the human body are tightly regulated by various signaling and feedback mechanisms. This section will describe the major regulators of energy balance in normal human physiology.

2.1: Physiologic control of energy intake

Energy intake is mainly a function of appetite or the drive to consume food, and appetite is primarily controlled by the brain, which receives signals from the periphery regarding the energy status of the body. One crucial region of the brain for appetite is the nucleus tractus solitarius of the brainstem [6]. During food intake, a large number of hormones are released into circulation by the gastrointestinal tract as it digests the food. These hormones, including cholecystokinin, glucagon-like peptide 1, amylin, and ghrelin, act on the vagus nerve, which has sensory neurons throughout the gut that respond to these hormones as well as mechanical changes such as distention and contraction [7]. The vagus nerve then integrates and transmits these signals to the brainstem, which is in communication with the hypothalamus as well as other areas of the brain. Most of these gut hormones signal satiety, except ghrelin, which signals hunger [8–11].

The arcuate nucleus of the hypothalamus in the brain is also able to detect the energy status of the body in order to regulate appetite [12]. Within the arcuate nucleus, there are two groups of neurons that regulate appetite—the NPY/AgRP and POMC, so named because these neurons produce neuropeptide Y (NPY) and Agouti-related peptide (AgRP) and proopiomelanocortin (POMC), respectively [13]. These neurons have opposite effects on appetite; NPY and AgRP are orexigenic, meaning that they stimulate food intake, while POMC is anorexigenic, meaning that it suppresses food intake. NPY, AgRP, and POMC neuropeptides exert their effects on appetite by acting on other nuclei within the hypothalamus, primarily the ventromedial hypothalamus and lateral hypothalamus. The ventromedial hypothalamus acts as the brain's satiety center and recent research has revealed a neural circuit from the ventromedial hypothalamus to the paraventricular thalamus that inhibits food intake [14]. On the other hand, the lateral hypothalamus acts as the brain's hunger center and likely mediates feeding behavior through GABA signaling to other areas of the brain [15,16].

The arcuate nucleus is sensitive to a variety of hormones and nutrients in circulation. By far the most well-studied influencers of arcuate nucleus activity are leptin and insulin. Leptin and insulin are often called adiposity signals in the literature because their levels are proportional to the amount of adipose tissue; thus, signaling by these hormones to the arcuate nucleus indicates energy storage levels in the body [17]. Indeed, both leptin and insulin have been shown to reduce food intake through their effects on the arcuate nucleus [18,19]. In addition, like the brain stem, the arcuate nucleus is also responsive to gut hormones, especially glucagon-like peptide 1, which has been shown to cause weight loss in mice specifically due to changes in appetite [20,21]. There is also evidence for arcuate nucleus sensing of glucose, fatty acids, and amino acids [6]. For example, glucokinase, an enzyme that is well-known regulator of glucose homeostasis in the liver and pancreas [22], has also been found in neurons of the arcuate nucleus and was found to increase food intake, with a preference for glucose-containing foods in rats, through NPY release [23].

2.2: Physiologic control of energy expenditure

As mentioned previously, the largest component of energy expenditure is the basal metabolic rate, which is mostly a function of fat-free body mass. Fat-free body mass, which is generally a sum of the muscle and organs, is much more metabolically active than adipose tissue and therefore contributes to most of resting energy expenditure [24]. The brain, musculoskeletal system, and other organ systems together use about 75% of resting energy expenditure. The brain on its own consumes about 240 kcal/kg/day, while adipose tissue generally consumes only 4.5 kcal/kg/day [25]. This is logical considering that adipose tissue mass consists primarily of stored lipids and considering the tremendous number of energy-consuming functions that are performed by our muscle and organs.

In humans, thyroid hormone controls the level of metabolic activity throughout the body and thus plays a major role in regulating the level of resting energy expenditure. Thyroid hormone stimulates breakdown of glucose, fat, and proteins to produce ATP, which is the basic energy unit used for metabolic processes. At the same time, it can modulate the efficiency of ATP production in the mitochondria through activating uncoupling proteins, resulting in heat production [26]. The importance of thyroid hormone in energy regulation is evident in individuals who have excess or inadequate thyroid hormone. For example, patients with Graves’ disease, an autoimmune condition that induces hyperthyroidism, often develop symptoms such as weight loss, tremors, heart palpitations, and heat intolerance [27], while those who have hypothyroidism commonly experience lethargy, cold intolerance, and weight gain [28].

In addition to regulation of basal metabolic rate, energy expenditure can also be altered in cold conditions through modulating non-shivering thermogenesis [29]. While shivering thermogenesis involves energy utilization and contraction of the muscles, non-shivering thermogenesis utilizes uncoupling of metabolic reactions in the mitochondria; nutrients are therefore broken down without the additional processes that produce ATP, resulting in heat production. In humans, brown adipose tissue plays a major role in non-shivering thermogenesis, and, because it breaks down fatty acids to fuel this process, regulators of non-shivering thermogenesis in this tissue are of particular interest as a potential weight loss treatment [30]. Indeed, cold exposure of human subjects increased energy expenditure and brown adipose activity, resulting in fat reduction [31]. Current research indicates that sympathetic nervous system activity from the hypothalamus, which sets body temperature, as well as thyroid hormone together activates thermogenesis in adipose tissue [30].

3: Regulation of metabolism

Thus far, we have discussed influencers of energy balance overall through describing regulators of energy intake and expenditure. However, to understand obesity development and its sequelae, one must also understand how metabolism, not just metabolic rate, is regulated. This section will provide a broad overview of glucose and lipid metabolism and the role of adipose tissue in these processes in normal physiology.

3.1: Glucose metabolism

After a meal, glucose taken in via the digestive system enters the bloodstream and is then absorbed by tissues and organs throughout the human body at different rates [32]. In humans, the brain, splanchnic bed (liver and gut), and skeletal muscle are the largest consumers of glucose; in total, these organs take up about 75% of glucose taken in after a meal. Simplistically, the pancreatic enzyme insulin controls glucose absorption and utilization by various organs after a meal through regulation of glucose transporters (GLUTs) found on the surface of cells [33]. The pancreas senses glucose in the bloodstream via GLUT2, a glucose transporter that is not sensitive to insulin and allows for passive diffusion of glucose into pancreatic islet cells [34]. In response to glucose, pancreatic islet cells secrete insulin into the bloodstream, and insulin then stimulates the translocation of GLUT4 to the surface of skeletal muscle and adipose tissue cells. GLUT4 is a high affinity glucose transporter, and movement of GLUT4 to the surface allows for a high rate of glucose intake into these cells [35]. Glucose consumed during a meal is also stored by the liver, which, like the pancreas, takes in glucose through GLUT2 [36]. As the liver is the center for glycogenesis, the storage of glucose as glycogen, this passive diffusion of glucose ensures that the liver only generates glycogen during times of high glucose gradient in the bloodstream, such as after a meal.

Conversely, during times of fasting, glucose levels in the bloodstream drop, triggering the release of glucagon from the pancreas and the breakdown of glycogen in the liver [37]. The breakdown of glycogen regenerates glucose, which is then transported out of the liver cells through GLUT2 [36]. These processes of glycogen breakdown and glucose generation are inhibited after meals by insulin, but insulin levels drop during fasting, allowing them to proceed [38].

In addition to direct control of glucose metabolism through modulation of GLUT activity, hormones can regulate glucose metabolism through the central nervous system [12]. As discussed previously, insulin and leptin are both able to affect brain signaling to suppress appetite. These same hormones have also been shown to activate parasympathetic and sympathetic neuronal pathways to the pancreas, liver, and muscles, inducing insulin secretion and glucose uptake, while decreasing glucagon and glucose release into the bloodstream [39].

3.2: Lipid metabolism

When fatty acids are consumed during food intake, the digestive system converts them into triglycerides, which consist of three fatty acid chains connected by a glycerol backbone, and binds them to lipoproteins to form chylomicrons that can be transported in the bloodstream for utilization [40]. In muscle and adipose tissue, the endothelium lining the vasculature contains lipoprotein lipase (LPL), which breaks down the triglycerides of chylomicrons into free fatty acids that can then be transported into cells [41]. Chylomicrons that are stripped of some of their triglycerides are called chylomicron remnants, and the triglycerides are repackaged in the liver as very low-density lipoproteins or VLDL. LPL similarly acts on triglycerides of VLDL, releasing free fatty acids for transport into cells. Free fatty acids transported into the cells are utilized for energy or stored in lipid droplets [42]. In adipocytes, lipid droplets are large and take up almost the whole volume of the cell, clearly demonstrating the fat storage function of adipocytes. As free lipids are toxic to the cell, the lipid droplet is structured not only to store fat and protect it from enzymatic degradation but also to sequester lipids from the rest of the