Chapter 041. Weight Loss (Part 1) doc

Weight Loss Weight Loss: Introduction Significant unintentional weight loss in a previously healthy individual is often a harbinger of underlying systemic disease.. During the routine m

Chapter 041 Weight Loss

(Part 1)

Harrison's Internal Medicine > Chapter 41 Weight Loss

Weight Loss: Introduction

Significant unintentional weight loss in a previously healthy individual is often a harbinger of underlying systemic disease During the routine medical examination, changes in weight should always be assessed; loss of 5% of body weight over 6–12 months should prompt further evaluation

Physiology of Weight Regulation

The normal individual maintains body weight at a remarkably stable "set point," given the wide variation in daily caloric intake and level of activity Because of the physiologic importance of maintaining energy stores, voluntary weight loss is difficult to achieve and sustain

Appetite and metabolism are regulated by an intricate network of neural and hormonal factors The hypothalamic feeding and satiety centers play a central role in these processes (Chap 74)

Neuropeptides such as corticotropin-releasing hormone (CRH), α-melanocyte-stimulating hormone (α-MSH), and cocaine- and amphetamine-related transcript (CART) induce anorexia by acting centrally on satiety centers

The gastrointestinal peptides ghrelin, glucagon, somatostatin, and cholecystokinin signal satiety and thus decrease food intake Hypoglycemia suppresses insulin, reducing glucose utilization and inhibiting the satiety center

Leptin is produced by adipose tissue, and it plays a central role in the long-term maintenance of weight homeostasis by acting on the hypothalamus to decrease food intake and increase energy expenditure (Chap 74)

Leptin suppresses expression of hypothalamic neuropeptide Y, a potent appetite stimulatory peptide, and it increases the expression of α-MSH, which acts through the MC4R melanocortin receptor to decrease appetite Thus, leptin activates a series of downstream neural pathways that alter food-seeking behavior and metabolism

Leptin deficiency, which occurs in conjunction with the loss of adipose tissue, stimulates appetite and induces adaptive responses including inhibition of

hypothalamic thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (GnRH)

A variety of cytokines, including tumor necrosis factor α (TNF-α), interleukin (IL) 6 (IL-6), IL-1, interferon γ (IFN-γ), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF), can induce cachexia (Chap 17) In addition to causing anorexia, these factors may stimulate fever, depress myocardial function, modulate immune and inflammatory responses, and induce a variety of specific metabolic alterations

TNF-α, for example, preferentially mobilizes fat but spares skeletal muscle Levels of these cytokines may be increased in patients with cancer, sepsis, chronic inflammatory conditions, AIDS, or congestive heart failure

Weight loss occurs when energy expenditure exceeds calories available for energy utilization (Chap 72) In most individuals, approximately half of food energy is utilized for basal processes such as maintenance of body temperature In

a 70-kg person, basal activity consumes ~1800 kcal/d

About 40% of caloric intake is used for physical activity, although athletes may use >50% during vigorous exercise About 10% of caloric intake is used for dietary thermogenesis, the energy expended for digestion, absorption, and metabolism of food

Mechanisms of weight loss include decreased food intake, malabsorption, loss of calories, and increased energy requirements (Fig 41-1) Changes in weight may involve loss of tissue mass or body fluid content

A deficit of 3500 kcal generally correlates with the loss of 0.45 kg (1 lb) of body fat, but one must also consider water weight [1 kg/L (2.2 lb/L)] gained or lost Weight loss that persists over weeks to months reflects the loss of tissue mass

Figure 41-1