Comorbidities of Obesity

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Obesity, especially visceral adiposity, is associated with morbidity and mortality through endocrine and mechanical processes. Clinical manifestations due to effects of obesity on the cardiovascular, respiratory, gastrointestinal, musculoskeletal, immune, and integumentary systems have been described. Further studies are needed to understand the pathologic processes underlying these clinical manifestations to improve disease prevention.

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Energy Homeostasis

The obesity epidemic is driven by an imbalance between energy intake, which is primarily behaviorally dependent, and energy expenditure, which is, in part, involuntary. This excess energy intake must be stored as fat in adipocytes, which are part of the body's largest endocrine unit. When energy expenditure is required, fat within the adipocytes is oxidized to release free fatty acids (FFAs) for gluconeogenesis and energy use.1, 2, 3

Pathophysiology of Increased Inactivity and Increased Energy Expenditure

Relatively little is known about the physiology of inactivity.

The pathologic adipocyte causes metabolic dysregulation

Simply put, obesity causes disease and dysfunction through 2 specific mechanisms: the interaction of hormones and regulatory cytokines produced by fat cells or adipocytes, and the mechanical adjustments associated with increased body mass. The clinical manifestations thus listed will occur in relation to the pathophysiologic mechanisms that cause that condition.

Cardiovascular Disease

Through the mechanisms of hyperglycemia, prothrombotic state, proinflammatory mediation, elevated blood pressure, and atherogenic dyslipidemia, visceral obesity increases the risk of cardiovascular disease.16, 18 This clustering of risk factors is clinically known as metabolic syndrome or insulin resistance syndrome. Metabolic syndrome is discussed in detail in a separate article.

The triad of the atherogenic process—atherosclerosis, inflammation, and thrombosis—is modulated by insulin

Skin manifestations of obesity

Obesity causes abnormalities in several functions of the skin, including in the effects on the sebaceous gland, sebum production, skin barrier function, and sweat production. It also promotes changes in lymphatics, collagen structure and function, wound healing, and subcutaneous fat.88 Two gene products are thought to mediate these skin abnormalities in obese patients, leptin and pro-opiomelanocortin.88 Some of the major problems with the skin are listed briefly.

The major metabolic

Musculoskeletal disability and pain associated with obesity

Obesity can cause several effects on musculoskeletal function. Adiposity is positively related to musculoskeletal pain and injury, especially in the back, hip, knee, ankle, and foot.92 Biomechanical adaptations caused by the sheer bulk and force of increased fat mass affect locomotion, balance, and strength and cause pain. Obese individuals have an altered center of gravity, and some inertia is apparent due to increased anteroposterior sway. Postural control and balance may be intact and is

Summary

Obesity, especially visceral adiposity, appears to be associated with several clinical conditions and can cause profound disease and disability. Adipocyte regulatory adipokines may be responsible for disease promotion and progression in several of these conditions. The sheer bulk of mass, weight, and displacement exacerbates others. Further studies will be needed to truly solidify these connections and to make them indisputable. Indeed Bays and colleagues2 propose labeling the metabolic

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