Physiology of appetite and weight Flashcards
What are the medical problems that are associated with obesity?
Metabolic syndrome / type 2 diabetes Cardiovascular disease, respiratory disease, liver disease Cancer Reproductive dysfunction Joint problems - gout and osteoporosis. Psychological morbidity
What is metabolic syndrome and what is the underlying pathophysiological mechanism?
Constellation of closely associated CV risk factors:
visceral obesity, dyslipidaemia, hyperglycaemia, hypertension.
Insulin resistance.
What is metabolic syndrome associated with?
Central (visceral) fat and BMI > 30
Outline the pathophysiology of obesity
Increased free fatty acids - gluconeogenesis, dyslipidaemia and lipolysis of visceral fat.
Pro-inflammatory cytokines TNF-alpha and IL-6 (from white adipose tissue) - insulin resistance. decreased expression of GLUT 4, decreased tyrosine kinase activity of insulin receptor.
What increases the risk of cardiovascular disease?
Metabolic syndrome plus increased: blood volume and blood viscosity vascular resistance hypertension left ventricular hypertrophy coronary artery disease stroke
How does obesity affect the respiratory system?
Obstructive sleep apnoea
Hypoxia / hypercapnia
Pulmonary hypertension - right heart failure
Accidents - daytime somnolence
How does obesity affect the GI and liver?
Non-alcoholic fatty liver, non-alcoholic steatohepatitis, may progress to cirrhosis. portal hypertension, hepatocellular cancer.
Gallstones and reflux.
How does obesity affect the reproductive system?
Polycystic ovarian syndrome - oligomenorrhoea, hirsutism, acne, subfertility, endometrial hyperplasia, insulin resistance.
Male hypogonadism.
Adverse pregnancy outcomes.
What are the causes of obesity?
Genetic factors
Environmental factors: poor diet, lack of exercise, socio-economic factors.
Fetal programming: stimuli/insults at critical periods have persistent biological effects, ‘stressors’ in utero (lower the birth weight, higher the morning cortisol as adults).
Gut microbiome: differences in gut bacteria due to high fat diet, transplantation of faecal material alters insulin sensitivity.
Other: hypothyroidism, Cushing’s syndrome.
What are the slow-acting hormones that regulate body weight?
leptin and insulin signals % body fat to hypothalamus - reduce food intake, increase energy expenditure.
What are the rapid-acting peptides that regulate meal sizes?
Released from GI tract.
Cholecystokinin (CCK) reduces eating
Ghrelin increases eating
PYY reduces eating and acts via hypothalamus.
Which brain structure is involved in regulating appetite and weight?
Arcuate nucleus of the hypothalamus
What is the function of leptin in humans and what occurs during obesity?
‘Starvation signal’, permissive effect on puberty.
Very rare: Leptin deficiency, mutation of leptin receptor.
Usually: increased [leptin] with increased fat, may be leptin resistant and reduced CNS leptin transport.
What are the pharmacological therapies available for obesity, what are their mechanism of action and adverse effects?
Orlistat inhibits lipases in lumen of gut. prevents hydrolysis of dietary fat into absorbable free fatty acids.
Flatulence, oily faecal leakage, diarrhoea, reduced absorption of fat soluble vitamins so have to supplement.
Metformin increases insulin sensitivity by increasing peripheral uptake of glucose, decreasing gluconeogenesis.
What are the surgical treatments for obesity?
Laparoscopic adjustable banding: restrictive only,
inject / withdraw saline to adjust diameter of band.
Roux-en-Y gastric bypass: restrictive, malabsorptive, alterations in gut hormones and bile acid flow contribute to weight loss.
