Adipose Tissue and Obesity PDF

CHAPTER 23 – Obesity & Disorders of Nutrition What are the three classifications of adipose tissue? WHITE ADIPOSE TISSUE BROWN ADIPOSE TISSUE BEIGE ADIPOSE TISSUE (WAT) (BAT) (bAT) Most adipose...

CHAPTER 23 – Obesity & Disorders of Nutrition What are the three classifications of adipose tissue? WHITE ADIPOSE TISSUE BROWN ADIPOSE TISSUE BEIGE ADIPOSE TISSUE (WAT) (BAT) (bAT) Most adipose tissue in body is Derived from muscle tissue & lipid Origin: located within white white adipose tissue droplets or vacuoles (multilocular) adipose tissue, particularly in and rich in mitochondria that subcutaneous fat depots are beige Origin: contain iron, giving a brown color. A subpopulation of white Derived from connective tissue adipocytes that also contains Visceral (central) stores Exposure to cold, activation of multiple mitochondria and Subcutaneous (peripheral) stores SNS/catecholamines, and UCP1 but not in the amounts Muscle groups providing triiodothyronine (T3) à stimulate associated with brown adipose mechanical protection & sliding brown adipose tissue to rapidly tissue of muscle bundles generate heat (activation of Bone marrow uncoupling protein 1 Contribution: thermogenic UCP1 – nonshivering Emerge within white adipose tissue Structure: normal structure thermogenesis) with chronic exposure to cold, with contains: UCP1 = promotes mitochondrial exercise and with energy 1. Macrophages respiration and dissipates expenditure 2. Mast cells chemical energy as heat from o Known as “beiging” of 3. Neutrophils increased glucose and free fatty white adipose tissue à 4. Fibroblasts acid oxidation disappears with elevated 5. Endothelial cells Occurs at a rate 50-fold greater ambient temps 6. Blood vessels than white adipose tissue and o Chronic exposure to cold à 7. Nerves protects against obesity and white adipose tissue 8. Precursor adipocytes metabolic syndrome transdifferentitation to beige White adipocytes à contain a Neonates generate body heat adipose tissue (thermogenic) single triglyceride fat droplet or from brown adipose tissue o Warm adaptation à beige vacuole primarily located in the adipose tissue reverts to Visceral à store fat as interscapular and perirenal white adipose tissue triglycerides (primarily in the regions Exercise àpromotes browning form of very-low density Adults have visible brown of white adipose tissue lipoprotein VLDL) derived adipose tissue (UCP1) on PET Leptin and insulin together from hepatic and dietary stores scan; common in lean promote beige adipose tissue individuals located in the neck, (increasing energy expenditure Contributes to regulation of energy supraclavicular, axillary, and weight loss) homeostasis à secretion of paravertebral and perineal Obesity à beige adipose tissue adipokines that function like regions. is diminished hormones. Low nutritional state à Leptin and adiponectin are Bone marrow adipose tissue minimally produced by brown stimulation of the sympathetic found in all bones, but greater in adipose tissue à little effect on nervous system and release of long bones. appetite and satiety epinephrine / norepinephrineà Contribution: releases adipokines activate hormone-sensitive with autocrine, paracrine, and Inverse relationship between endocrine effects. lipase àlipolysis in white amount of brown adipose tissue, Increase levels = osteoporosis. adipose tissue à release free BMI, and age Variation of brown fatty acids and glycerol into adipose tissue and “brite” circulation adipocytes may participate in natural regulation of weight reduction 1 Know how adipose tissue provides insulation, mechanical support, and energy to the body. Adipose tissue: provides insulation and mechanical support and the body’s major energy reserve to fuel other tissues. Adipose tissue is an endocrine organ, and adipocytes secrete adipokines Adipocytes: fat storing cells, secrete adipokines Adipokines: Cell-signaling proteins that function like hormones, having autocrine, paracrine, and endocrine actions (regulation of energy homeostasis) Adipokines include all the biologically active substances synthesized by white adipose tissue Function in the control of food intake and energy expenditure, lipid storage, insulin sensitivity, immune and inflammatory responses, coagulation, fibrinolysis, angiogenesis, fertility vascular homeostasis, BP regulation, & bone metabolism. Store excess energy in the form of triglycerides (triglycerol) synthesize triglycerides from glucose mobilize energy in the form of free fatty acids (FFAs) and glycerol Most abundant adipose tissue in the body located in visceral white adipose tissue (central) and subcutaneous white adipose tissue (peripheral) stores, muscle groups (provides mechanical protection & sliding of muscle bundles), and bone marrow. Visceral adipocytes store fat as triglycerides primarily in the form of very-low-density-lipoprotein (VLDL) à derived from hepatic and dietary sources Low nutritional state à stimulation of the b-adrenergic SNS, release of catecholamines (Epi & Norepi) activate hormone-sensitive lipase à triggering lipolysis in white adipose tissue to release FFAs and glycerol into circulation. Pancreatic insulin can inhibit lipolysis by activation of insulin receptors in adipocytes. With obesity- adipocytes are resistant to insulin lipolysis. Positive energy balance à excess fat stored in mature white adipocytes, which hypertrophy and adipogenesis (hyperplasia, formation of new fat cells from preadipocytes) Chronic positive energy balance can overwhelm adipogenesisà fat storage only depends on hypertrophy The key physiological functions of white adipose tissue are insulation and energy storage Obesity à excess visceral adipose tissue is closely linked to metabolic complications (insulin resistance and type 2 diabetes) Brown adipose tissue: o participates in non-shivering thermogenesis through lipid oxidation 2  o distinct brown color of brown adipose tissue is attributed to its high mitochondrial density à critical for heat generation and lipid oxidation; § Proposed that brown adipose tissue is limited to neonates and is gradually replaced by white with aging § positron emission tomography/computed tomography studies have shown that brown adipose tissue is viable and functional in human adult § Various adipose tissues act as central regulators of energy homeostasis by storing excess energy as well as by controlling thermogenesis How does obesity produce a state of chronic, low-grade inflammation in white adipose tissue (WAT)? Obesity produces a state of chronic, low-grade inflammation (metabolic triggered inflammation) in WAT Macrophages, lymphocytes (proinflammatory CD8+ T cells), neutrophils, and mast cells à infiltrate enlarged adipocytes à release inflammatory cytokines (e.g., TNF-α, and IL-6). Macrophages change their phenotype from anti-inflammatory expression of cytokines (M2 macrophages) à expression of proinflammatory cytokines (M1 macrophages). The mechanisms of macrophage infiltration à related to adipocyte senescence, necrosis, and death. The inflammatory state is supported by à increased levels of leptin and resistin and decreased levels of adiponectin, and escalation of eicosanoid-generating prostaglandins and leukotriene B4 Inflammatory state and accelerated lipolysis à insulin resistance, metabolic syndrome, and complications of obesity (type 2 diabetes mellitus, cardiovascular disease, and cancer) What are the genetic, metabolic, and environmental factors that contribute to obesity? Genetic: Genotype and gene-environment interactions are important predisposing factors Single-gene defects (monogenic) are rare, and obesity is usually polygenic and associated with other phenotypes such as endocrine disorders (DM, hypothyroidism), and intellectual disability (Down and Prader-Wille syndromes) Single gene defects include the melanocortin-4 receptor gene (aka obesity gene), and leptin-receptor gene All single-gene defects are directly or indirectly related to leptin and melanocortin pathways (decrease appetite and regulate energy homeostasis) Metabolic: Cushing disease and syndrome, polycystic ovarian syndrome, growth hormone deficiency, hypothyroidism, & hypothalamic injury. Environmental factors: socioeconomic status (both high and low incomes), food intakes (low energy, energy-dense foods, and physical inactivity. Obesity is also associated with adverse social and psychological consequences (depression and mood disorders). 3 How does the arcuate nucleus (ARC) regulate food intake and energy metabolism by balancing the opposing effects of two sets of neurons? Located in hypothalamus à arcuate nucleus àbalancing the opposing effects of two sets of neurons à regulates food intake and energy metabolism 1. AgRP/NPY neurons à produces agouti-related protein (AfRP) and neuropeptide Y (NPY) a. Promote appetite, stimulate eating, and decrease metabolism (anabolic) b. Known as orexigenic neurons – stimulated by molecules called orexins 2. POMC/CART neurons à synthesize pro-opiomelanocortin-producing (POMC-producing) peptide and cocaine-and-amphetamine-regulated transcript (CART) a. Suppress appetite, inhibit eating, and increase metabolism b. Known as anorexigenic neurons – stimulated by molecules called anorexins Orexins (appetite Stimulants) Anorexins (appetite suppressants) Neuropeptide Y (NPY) Leptin Melanin-concentration hormone (MCH) Insulin Agouti-related protein (AgRP) Cholecystokinin (CCK) Ghrelin Glucagon-like peptide 1 (GLP-1) Galanin Peptide YY (PPY) Orexins A & B Corticotropin-releasing factor (CRF) Endocannabinoids Urocortin (A CRF satiety signaling hormone) Cortisol Cocaine0 and amphetamine-regulated transcript (CART) Alpha-melanocyte-stimulating hormone Bombesin Serotonin Calcitonin What are the methods of estimating or measuring the amount of adipose tissue in order to screen for obesity. 1. Anthropometric measurements (weight, height, and circumferences of various body diameters à waist-to- hip ratios and waist circumference) 2. Skinfold thickness (measured via skinfold calipers) 3. Ultrasound à measure peripheral body fat 4. Bioelectric impedance and underwater hydrostatic weighing to calculate total body fat 5. DEXA scans (dual energy x-ray absorptiometry) the ONLY method for directly measuring total body fat Use anthropometric and body diameter measurements to calculate BMI 1. Body mass indices (BMI) have been established based on height, weight, age, gender, and ethnicity (adult) a. BMI> than 25 kg/m2 is overweight b. BMI> than 30 kg/m2 is obesity c. BMI charts = ages 2 to 20 years 2. Waist circumference à adds information to assist with disease risk assessment (measures amount / distribution of body fat) 4 What is the differences between malnutrition and starvation. MALNUTRITION Define: lack of nourishment from inadequate amounts of calories, protein, vitamins, or minerals caused by: improper diet alterations in digestion or absorption chronic disease combination of these factors STARVATION Define: reduction in energy intake leading to weight loss. 1. Therapeutic Short Term: a. initial rapid weight loss that reinforces the individual’s motivation to diet (ex. weight loss programs) 2. Therapeutic Long Term: a. facilitate rapid weight loss in morbidly obese persons (used in medically controlled environments) 3. Pathologic Long Term: a. long term starvation (poverty; chronic diseases of cardiovascular, pulmonary, hepatic and digestive systems; malabsorption syndromes, HIV infection and cancer) Short term starvation (extended fasting): Long term starvation: Duration: several days of total dietary abstinence or Duration: begins after several days of dietary deprivation. abstinence and eventually causes death. Patho: Body responds with mechanisms to protect Patho: absolute depravation of food à marasmus or protein mass protein-energy malnutrition (loss of muscle mass & For 4 to 6 hours after the last meal à body is in a body fat depletion) well-fed state & its energy requirement are Kwashiorkor à protein deprivation in the supplied by glucose from recently ingested presence of carbohydrate intake à loss of carbohydrates muscle mass with sustained body fat Once all available energy has been absorbed from the Marmasmic Kwashiorkor à combination of intestine à glycogen in the liver is converted to chronic energy deficiency and chronic or acute protein deficiency and inadequate glucose through glycogenolysis (splitting of glycogen micronutrients (edematous, severe, childhood into glucose) which takes about 4 to 8 hours to peak malnutrition) à gluconeogenesis begins Cachexia (cytokine induced malnutrition): Gluconeogenesis à formation of glucose physical wasting with loss of weight and muscle from noncarbohydrate molecules (lactate, atrophy, fatigue, and weakness. pyruvate, amino acids) and glycerol portion 1. Inflammatory mediators (TNF-a, interferon- of fats from lipolysis y, IL-1, IL-6) and increased catabolic Both glycogenolysis and glycogenesis takes response à cachexia of advanced cancer place in the liver 2. Cancer, AIDS, TB, and other chronic Both processes deplete stored nutrients and diseases contribute to cachexia thus cannot meet the body’s energy needs 3. NOT the same as food deprivation starvation; indefinitely. a healthy person’s body can adjust to Proteins continue to be catabolized to a starvation by slowing the metabolic rate – minimal degree à providing carbon for but in cachexia, the body cannot adjust. synthesis of glucose 5  Major characteristic of long-term starvation: decreased dependence on gluconeogenesis and increased use of ketone bodies as cellular energy Decreased insulin levels and increased glucagon levels, cortisone, epinephrine, and growth hormones àlipolysis in adipose tissueà liberates fatty acids àsupply energy to cardiac and skeletal muscle cells and ketone bodies à sustain brain tissue. o Fatty acid (ketone body) oxidation meets most of the energy needs of cells (some glucose is still needed as fuel for brain tissue) Supply of adipose tissues is depleted à proteolysis begins o Breakdown of muscle and visceral protein is the last process the body engages to supply energy for life Death à severe electrolyte balance and loss of renal, pulmonary and cardiac function Treatments: Starvation à inadequate ingestion of appropriate nutrients Medically induced starvation à body is maintained in a ketotic state until the desired amount of adipose tissue has been lysed Starvation by chronic disease, long term illness, malabsorption syndromes, chronic eating disorders enteral or parenteral nutrition Note: Refeeding Syndrome can occur when initiation of parenteral/enteral nutritional therapy and can be life threatening. Care must be taken to start feedings at about 20 kcal/kg/day. 6 What is anorexia of aging and what are the risk factors Define: a decrease in appetite or food intake in older adults and can occur in illness-free individuals and in the presence of an adequate food supply. Cause: multiple age-related changes (reduced energy needs, waning hunger, diminished senses of smell and taste, decreased production of saliva, altered gastrointestinal satiety control mechanisms and the presence of comorbidities) Central aging à decreased orexigenic signals (levels of ghrelin or ghrelin resistance and reduced NPY/NPY receptors) and increased anorexigenic signals (decreased levels of leptin, insulin, PPY, and CCK) à loss of appetite and diminished food intake Chronic low-grade inflammation with elevated cytokines à delayed gastric emptying and decreased motility of the small intestine Risk factors: functional impairments and deficiencies (e.g., loss of vision, poor dentition, inability to prepare foods) medical and psychiatric conditions (such as malabsorption syndromes and depression) loneliness and grief medications, including polypharmacy social isolation abuse or neglect Complications: malnutrition, physical frailty, mitochondrial dysfunction, reduced regenerative capacity, increased oxidative stress, and imbalanced hormonal levels Treatments: supportive strategies (improved food access and appearance, dental and eye care, social stimulation) 7