Porth's Essentials of Pathophysiology, 4e

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Disorders of Nutritional Status

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factor, and the percentage of dietary fat independent of total caloric intake may play a part in the development of obesity. Psychological factors include using food as a reward, comfort, or means of getting attention. Eating may be a way to cope with tension, anxiety, and mental fatigue. AdiposeTissue Adipose tissue is no longer simply viewed as a reser- voir for energy storage. Adipose tissue is now known to express and secrete a variety of bioactive peptides, known as adipocytokines (e.g., leptin, tumor necrosis factor- α [TNF- α ], interleukin-6 [IL-6]) that have auto- crine, paracrine, and endocrine effects on the brain, liver, skeletal muscle, and other tissues of the body. 24 In addition, adipose tissue expresses numerous recep- tors that allow it to respond to afferent signals from traditional hormone systems as well as the central ner- vous system. Through this interactive network adipose tissue is integrally involved in coordinating a variety of physiologic processes including energy metabolism, neuroendocrine function, and immune function. It is the dysfunctional aspects of these processes that are impli- cated in the pathogenesis and adverse effects of adipose tissue excess or obesity. AdiposeTissue as an Endocrine Organ Adipose tissue is now recognized as an endocrine organ that produces several hormones, including leptin , an important mediator of body weight, and adiponec- tin , which regulates sensitivity to insulin and may be involved in the pathogenesis of type 2 diabetes. 24,25 Leptin (from the Greek meaning “thin”), a peptide released from adipocytes, has led to renewed interest in the function of adipose tissue and its role in energy homeostasis. Leptin acts through binding to and activa- tion of specific leptin receptors found in several periph- eral tissues and in many areas of the brain, including specific regions of the hypothalamus. Receptors in these hypothalamic regions are known to be involved in appetite, food intake, sympathetic nervous system activity, temperature regulation, and insulin release by the pancreatic beta cells. Leptin levels rise following food intake, signaling the sensation of satiety, and fall during fasting, stimulating the sensation of appetite. Congenital leptin deficiency has been associated with hyperphagia (excessive eating) and obesity, impaired thermogenesis, insulin resistance, and hyperlipidemia, all reversed by leptin treatment. 25 The biology of leptin in normal individuals and its involvement in obesity and obesity-related diseases is uncertain. Adipose tissue also secretes adiponectin , which regu- lates sensitivity to insulin and may be involved in the pathogenesis of type 2 diabetes. 24,25 Whereas dysfunc- tional adipose tissue increases the levels of certain other hormones and adipocytokines, the levels of adiponectin are decreased, leading to decreased insulin sensitivity, proatherosclerosis, and a proinflammatory milieu that can predispose the individual to metabolic syndrome

(see Chapter 33) and its associated complications (includ- ing type 2 diabetes and cardiovascular disease). 15,16 AdiposeTissue and the Inflammatory Process Recent evidence suggests that excess adipose tissue is also associated with a chronic inflammatory response, which is characterized by abnormal cytokine produc- tion; increased synthesis of acute-phase reactants, such as C-reactive protein; and activation of proinflammatory signaling pathways. 26 Systemic chronic inflammation has been proposed to have an important role in the pathogen- esis of obesity-related insulin resistance and development of type 2 diabetes. It might also contribute to a state of endothelial dysfunction, an abnormal lipid profile, hyper- tension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular dis- ease. 26,27 Although there is evidence that the proinflamma- tory pathways are activated in adipose tissue in obesity, the source of the inflammatory mediators remains unclear. Besides adipocytes, adipose tissue contains a connective tissue matrix and macrophages, which may contribute to the production of inflammatory mediators. Types of Obesity Two types of obesity based on distribution of fat have been described: upper body and lower body obe- sity. Upper body obesity is also referred to as central , abdominal , or visceral obesity. Lower body obesity is also known as peripheral or gluteal-femoral obesity. Persons with upper body obesity are often referred to as being shaped like an “apple,” compared with those with lower body obesity, who are more “pear” shaped (Fig. 10-3). The obesity type is determined by dividing the waist by the hip circumference. A waist-to-hip ratio greater than 1.0 in men and 0.8 in women indicates upper body obesity. Research suggests that fat distribu- tion may be a more important factor for morbidity and mortality than overweight or obesity.

A B FIGURE 10-3. Distribution of adipose tissue in (A) upper body or central (visceral) obesity and (B) lower body or peripheral (subcutaneous) obesity. People with upper body obesity are often described as having an “apple-shaped” body and those with lower body obesity as having a “pear-shaped” body.