Chapter 23 Obesity/starvation/anorexia (week 11)

Functions regulated by adipokines

-appetitive -food intake and energy expenditure -lipid storage -insulin secretion and sensitivity -immune and inflammatory responses -coagulation -fibrinolysis -angiogenesis -fertility -blood pressure -bone

Leptin resistance

A condition where high Leptin levels are ineffective in inhibiting orexigenic satiety and promotes overeating and excessive weight gain (cause is unknown)

Anorexia of aging

A decrease in appetite of food intake in older adults in the presence of adequate food supply (can occur in non illness) Etiology: reduced energy needs, waning hunger, diminished senses of smell and taste, decreased saliva production, presence of comorbidities, etc

Anorexia nervosa

A psychological cause of long term starvation

Marasmic Kwashiorkor

A severe childhood malnutrition & edematous A combination of chronic energy deficiency and chronic or acute protein deficiency and inadequate micronutrient

Obesity produces what

A state of chronic low grade inflammation in WAT

What is the cellular basis of obesity

Adipocyte

Obesity

An increase in body adipose tissue and an endocrine and metabolic disorder where caloric intake exceeds caloric expenditure in genetically susceptible individuals

Glucagon like peptide 1 (GLP-1)

Anorexigenic hormone secreted by intestinal endocrine cells when nutrients enter the small intestine Stimulates pancreatic glucose dependent insulin secretion, decreases blood glucose levels, delays gastric emptying, suppresses appetite, increases satiety, and increases energy expenditure May be decreased in obese individuals

Enlarged adipose cell size results in what

Apoptosis, local hypoxia, cell and mechanical stress, and promotes inflammation

Long term starvation

Begins after several days of dietary abstinence and eventually causes death from proteolysis -protein energy malnutrition (marasmus): loss of muscle mass, body fat depletion, and absence of edema -protein deprivation in the presence of carbs intake (kwashiorkor): loss of muscle mass with sustained body fat and peripheral edema

Adipokines

Cell signaling proteins that function like hormones, having autocrine, paracrine, and endocrine actions -include all the biologically active substances synthesized by WAT -excess WAT causes dysregulation of the secretion and function of adipokines, contributing to the many complications of obesity

Liptoxicity

Chronic positive energy balance and obesity can overwhelm fat storage by adipocytes, resulting in altered lipid metabolism and insulin resistance Cellular function and death can occur when utilization capacity is exceeded

Brown adipose tissue (BAT)

Derived from muscle tissue Rich in mitochondria that contain iron (gives BAT the brown color) Neonates generate body heat from BAT (intrascapular and perirenal regions)

Bone marrow adipose tissue (MAT)

Found in all bones Increases in obesity and age in long bones Excessive mat is associated with osteoporosis and fracture

Central Leptin Resistance

High Leptin levels are ineffective at decreasing appetite and energy expenditure, a condition associated with obesity

The inflammatory state is supported by what

Increases Leptin, decreased adiponectin, and increased resistin

malnutrition

Lack of nourishment from inadequate amounts of calories, protein, vitamins, or minerals Etiology: improper diet, alterations in digestion or absorption, chronic disease, or a combination of factors

what is the product of the obesity gene

Leptin is and is expressed primarily by adipocytes Leptin levels increase after eating and act on the hypothalamus to inhibit orexigenic neurons and stimulate anorexigenic neurons to suppress appetite and increase energy expenditure

Beige adipose tissue (bAT)

Located in WAT particularly in the subcutaneous fat stores A sub population of white adipocytes that also contain multiple mitochondria but not like the amount in BAT bAT disappear with ambient temperatures and with warm adaption revert to WAT Leptin and insulin together promote bAT, increasing energy expenditure and weight loss (bAT is diminished in obesity p)

Anorexia

Loss of appetite

Excess fat is stored where

Mature white adipocytes when energy balance is positive

White adipose tissue (WAT)

Most adipose tissue in the body -derived from connective tissue -located in visceral or subcutaneous stores

Ghrelin resistance

Obesity is associated with a decreased plasma level of Ghrelin and plasma levels do not fall after eating

Adipokines can function as what

Orexins and anorexins and provide peripheral signals for the control of food intake and energy expenditure

Ghrelin

Produced by the stomach gastric mucosa in response to hunger and stimulus food intake and fat storage Prevents life threatening hypoglycemia by inhibiting insulin secretion and stimulating glucagon secretion Increases in response to fasting and chronic caloric restriction and decreases after food intake Stimulate the release of GH by the anterior pituitary

Adiponectin

Produced primarily by visceral adipose tissue but also by cardiomyocytes and skeletal muscle, increases energy expenditure Also has insulin- sensitizing and anti- inflammatory properties

Orexigenic neurons (stimulated by orexins)

Promote appetite, inhibit eating, and increases metabolism

Adipose tissue

Provides insulation and mechanical support Secretes hormone like signaling molecules called adipokines Contributes to immune cell function Major energy reserve to fuel other tissues

Bulimia nervosa

Psych disorder with recurrent episodes of binge eating with recurrent inappropriate compensatory behavior in order to prevent weight gain -self induced vomiting -misuse of laxatives -misuse of diuretics or other meds -fasting -excessive exercise Binge eating and innapropriate compensatory behaviors both occur on average at least once a week for 3 months

Starvation

Reduction in energy intake related to inadequate food sources leading to weight loss Etiology: poverty, chronic disease, malabsorption syndromes, HIV, malignancy

Peptide YY (PYY)

Released from intestinal endocrine cells in response to nutrients entering the intestine -inhibits gastric motility and mucosal secretion -decreases with obesity -increases satiety and decreases appetite by acting on the medullary brain stem

Cholecystokinin (CCK)

Secreted by proximal small intestine cells after food intake -gallbladder contraction, release of pancreatic enzymes and insulin, satiation, and reduced food intake

Short term starvation

Several days of total dietary abstinence or deprivation -once all available energy has been absorbed from the liver, glycogen in the liver is converted to glucose (glycogenolysis), and hepatic glucogenesis -depletes stored nutrients and body's energy needs are not met

Cachexia (cytokine induced malnutrition)

Skeletal muscle wasting, causing muscle atrophy with involuntary loss of weight leading to fatigue, and weakness Muscle atrophy results from negative protein and energy balance due to reduced food intake and abnormal metabolism Etiology: malignancy, heart failure, COPD, AIDS, RA, TB, etc

Anorexigenic neurons (stimulated by anorexins)

Suppress appetite, inhibit eating, and increases metabolism

Central regulation of food intake and energy balance

The arcuate nucleus (ARC) in the hypothalamus regulates food intake and energy metabolism by balancing the opposing effects of two sets of neurons

Peripheral regulation of food intake and energy balance

The gastrointestinal (GI) tract secretes a number of hormones that also control hunger and satiety