RGHR

Introduction

The adipose tissue is the largest endocrine organ in humans. It is mainly located beneath the skin (subcutaneous adipose tissue) but also in other areas (e.g., visceral adipose tissue and ectopic adipose tissue) [1-5]. It plays a vital role in the survival of humans. In addition to its mechanical and storage properties, adipose tissue has important metabolic and endocrine functions.

Excess adiposity is defined as the expansion of adipose tissue (e.g., hypertrophy and hyperplasia) leading to overweight/obesity and subsequent morbidity and mortality [6-8]. Obesity is a major health problem worldwide inflicting high cost to the society [9,10].

Management of excess adiposity requires multidisciplinary approaches including lifestyle (e.g., diet, exercise, and behavioral change), food supplements, drugs, medical devices, gut microbiome modulation, body contouring, and bariatric surgery [6,11-24].

Normal Adipose Tissue

The adipose tissue is the largest endocrine organ in humans (Figure 1). In normal young adults, the adipose tissue represents 8 to 19% of total body mass in men and 21 to 32% in women. It contains adipocytes, connective tissue, nerve tissue, vascular cells, and immune cells [2,5]. There are three types of adipose tissue, white adipose tissue (the predominant type), brown adipose tissue, and beige adipose tissue (new classification) [1-5].

Figure 1: The adipose tissue is the largest endocrine organ in humans. Copyright katerynakon (Kateryna Kon)/Depositphotos Inc.

Distribution

White Adipose Tissue

The white adipose tissue is located beneath the skin (subcutaneous adipose tissue) and other areas (e.g., visceral adipose tissue and ectopic adipose tissue) [1-5,25]. The subcutaneous white adipose tissue is the most abundant component of adipose tissue in lean subjects, representing approximately 80% of total adipose tissue (Figure 2). The visceral white adipose tissue is localized around several internal organs (e.g., epicardial adipose tissue). The ectopic white adipose tissue is localized within internal organs (e.g., liver and pancreas). These adipose tissues represent 6 to 20% of total adipose tissue.

Figure 2: The subcutaneous white adipose tissue represents approximately 80% of total adipose tissue in lean subjects. Copyright tussiksmail.gmail.com (Victor Josan)/Depositphotos Inc.

Brown Adipose Tissue

The brown adipose tissue is located primarily in the cervical, axillary, and paraspinal regions [1,2,5,25]. Brown adipose tissue represents approximately 1-2% of total adipose tissue [5].

Beige Adipose Tissue

The beige adipose tissue represents a new classification. It has been described as the presence of brown adipocytes within white adipose tissue [4,5].

Regulation

The white, brown, and beige adipose tissues are innervated by the sympathetic nervous system whose activation is necessary for the functions of different adipose tissues [4]. The metabolism of adipose tissue is also influenced by several hormones including growth hormone, leptin, insulin, and cortisol (non-exhaustive list).

Role

The white adipose tissue plays a vital role in the survival of humans. It is involved in heat insulation, dermal infection barrier, mechanical protection (cushion), and storage of excess energy as triglycerides. It is a highly active metabolic and endocrine organ involved in the production of adipocytokines (e.g., leptin, adiponectin, resistin, omentin, interleukin 6, and tumor necrosis factor alpha) which act at both local (autocrine, paracrine) and systemic (endocrine) levels, affecting energy homeostasis, insulin sensitivity, and neuroendocrine, cardiovascular, and immune functions (Figure 3) [1,2,4,5,25].

Figure 3. The white adipose tissue produces several factors called adipocytokines with autocrine, paracrine, and endocrine functions. Copyright edesignua (Tetiana Zhabska)/Depositphotos Inc.

The brown adipose tissue is involved in thermoregulation. It transfers energy from food into heat [1,4,5]. Although the mass of the brown adipose is relatively small, its contribution to metabolic health is important. It produces adipocytokines and exclusively secretes molecules called batokines (e.g., fibroblast growth factor). The exact role of the beige adipose tissue has yet to be determined [4,5].

Physiological Variations

Age

With aging, adipose tissue undergoes significant changes in mass, distribution, composition, and secretory profile due to chronic positive calorie balance, reduced physical activity, and lower basal metabolic rate [1,2,4,25,26]. White adipose tissue mass increases, peaks around 65-70 years, but decreases in very old ages. The increase in visceral adipose tissue mass is more pronounced in women [26]. There is an increase in the levels of most adipocytokines (e.g., leptin, adiponectin, resistin, interleukin 6, and tumor necrosis factor alpha) with aging [25]. Elevated levels of pro-inflammatory adipocytokines (e.g., interleukin 6 and tumor necrosis factor alpha) can negatively impact aging and lifespan by promoting chronic diseases (e.g., obesity, type 2 diabetes, and ischemic heart disease). In contrast, elevated levels of adiponectin, an anti-inflammatory adipocytokine, can be beneficial and responsible for the favorable metabolic phenotype of centenarians, explaining their extended longevity. Brown adipose tissue and beige adipose tissue masses also decrease with aging.

Gender

Overall, men have a lower total body adipose tissue percentage than premenopausal women but have more adipose tissue in the abdominal subcutaneous and visceral areas [3,25].

Disorders of Adipose Tissue

Disorders of adipose tissue affect mainly white adipose tissue. They include accumulation of lipophilic endocrinedisrupting chemicals (EDCs) responsible for several medical disorders, excess adiposity (e.g., hypertrophy and hyperplasia) leading to overweight/obesity and related comorbidities, and deficient adiposity (e.g., lipodystrophies).

Accumulation of EDCs

EDCs are a heterogenous group of exogenous chemicals or chemical mixtures that interfere with the action of hormones. EDCs are present in a variety of products [27]. The majority of EDCs are highly lipophilic, stored in adipose tissue, and resistant to degradation. The chronic release of EDCs stored in adipose tissue can promote several medical disorders including diabetes, obesity, nonalcoholic fatty liver disease, infertility, and cancers (non-exhaustive list) [27].

Excess Adiposity

The body mass index (BMI) is used as a surrogate marker for adipose tissue mass and for defining overweight/obesity [6]. Overweight is defined as a BMI ≥ 25 and < 30 kg/m² and obesity as a BMI ≥ 30 kg/m². In some Asian countries (e.g., China and Japan), the thresholds to define overweight and obesity are lower.

The BMI may not be an accurate tool to assess obesity since it does not take body composition into account.

The expansion of the adipose tissue occurs when energy intake exceeds energy expenditure. The adipose tissue can expand by either hypertrophy (increase in the size of adipocytes) or hyperplasia (increase in the number of adipocytes). The excess adiposity leads to overweight/obesity. The subcutaneous white adipose tissue acts as a buffer for excess lipid storage (Figure 4). When this storage capacity is exceeded due to limited hypertrophy or hyperplasia, the excess fat accumulates outside of the subcutaneous area, causing visceral obesity. Obesity is a major health problem worldwide. Its prevalence has doubled in more than 70 countries since 1980 [8]. The number of adult subjects with obesity is around 650 million worldwide.

Figure 4: Excess fat deposits in the subcutaneous areas. Copyright CLIPAREA (Peter Lecko)/Depositphotos Inc.

Causes

The pathogenesis of excess adiposity leading to obesity is complex. Several factors can contribute (e.g., genetic, sociocultural, behavioral, environmental, and medical factors) (non-exhaustive list) [6].

Consequences

Excess adiposity leading to obesity is associated with increased morbidity/mortality and high cost for the society [6-10]. Multiple organs and systems are impacted by obesity (Figure 5) (Table 1). Visceral obesity is strongly associated with cardiometabolic risk factors, especially in women [28]. Nearly 4 million subjects die each year from the consequences of obesity. People with obesity spend approximately 30% more on medical care than people without obesity. The annual worldwide cost of obesity is more than $2 trillion.

Figure 5: Organs impacted by obesity (non-exhaustive list). Copyright Kittichai (Kittichai Songprakob)/Depositphotos Inc.

Table 1: Systems impacted by obesity and the resulting comorbidities (non-exhaustive list).

Management

In addition to preventive measures, management of excess adiposity requires multidisciplinary approaches including lifestyle (e.g., diet, exercise, and behavioral change), food supplements, drugs, medical devices, gut microbiome modulation, body contouring, and bariatric surgery (Table 2) [6,11-24].

Table 2. Anti-obesity tools approved and/or available in the USA (non-exhaustive list).

Any medical condition that can contribute to weight gain should be treated as appropriate. Subjects receiving medications known to induce weight gain should consider alternative treatment when possible.

Even a modest weight loss can decrease the risk of several comorbidities of obesity [6,29]. The ideal is a weight loss of at least 5 to 10% over 6 to 9 months followed by a long-lasting weight maintenance. Unfortunately, many subjects do not achieve longlasting benefits of weight loss due to difficulty with compliance as well as body adaptation in response to weight loss.

Lifestyle

For a clinically meaningful weight loss, an intense lifestyle intervention that includes in-person individual or group sessions is recommended [6]. Diet is an important component in the management of obesity (Figure 6). Several hypocaloric diets have been proposed. They differ in the amount of calorie (e.g., low calorie or very-low calorie) and macronutrient composition (e.g., low or high carbohydrate, low or high fat, and high protein) [11]. Hypocaloric diets result in weight loss regardless of macronutrient composition. The extent of caloric restriction should be adjusted to the baseline caloric intake and the physical activity.

Figure 9: Obesity is associated with important changes in gut microbiome (dysbiosis). Copyright ovocheva (Zhanna Kocherzhuk)/Depositphotos Inc.

Gut microbiome can be modulated to change the host metabolism and manage obesity. The tools include diet, prebiotics, probiotics, synbiotics, bariatric surgery, and gut microbiota transplantation. Diet (e.g., hypocaloric, low-fat, high-protein, and high-fiber diets) can increase the richness of gut microbiome and decrease the Firmicutes to Bacteroidetes phyla ratio and promote weight loss. Prebiotics (e.g., oligofructose-enriched inulin) and probiotics (e.g., fermented milk containing Lactobacillus gasseri species), by modulating gut microbiome, can manage weight gain and obesity. Bariatric surgery causes significant favorable changes in gut microbiome independently of body weight and further enhances weight loss. Clinical data on fecal microbiota transplantation in obesity are relatively limited but promising (Table 11) [18].

Table 11: Tools used for gut microbiome modulation in the management of obesity. Table modified from Heshmati HM (18).

The cost of gut microbiome modulation in the management of obesity is reported in Table 12.

Table 12: Average cost (without insurance coverage) of tools used for gut microbiome modulation in the management of obesity in the USA. Table modified from Heshmati HM (18).

Body Contouring

The remodeling of the body contour is achievable through several invasive or noninvasive methods. Liposuction is the most popular cosmetic procedure in the world and is considered safe for remodeling the body contour [19-22]. It is mainly used for the correction of deep and superficial fat accumulations. Small incisions are performed in different places depending on the area that needs treatment. A cannula is inserted, and the adipose tissue is broken loose from the fibrous stroma with multiple crisscross movements and removed (Figure 10). When properly performed, complications of liposuction are rare. To improve aesthetic results, excision surgery may be necessary for removing the excess skin.