Obesity and the endocrine control of food intake Flashcards
How is the arcuate nucleus involved in controlling food intake?
Above median eminence
Circumventricular region/organ
Incomplete blood brain barrier, allows access to peripheral hormones
Integrates peripheral and central feeding signals
Two neuronal populations: stimulatory (NPY/Agrp neuron) and inhibitory (POMC neuron)
What are the 2 neuronal populations of the arcuate nucleus?
NPY/Agrp neurons increase appetite
POMC neurons decrease appetite
Both sets of neurons extend to other hypothalamic and extra-hypothalamic regions
How do human CNS mutations affect appetite?
No NPY or Agrp mutations associated with appetite discovered in humans.
POMC deficiency and MC4-R mutations cause morbid obesity.
Mutations not responsible for the prevalence of obesity- but useful to explain signalling.
What is leptin?
Codes for 167 amino acid hormone.
Low when low body fat.
High when high body fat.
Central or peripheral administration decreases food intake and increases thermogenesis.
Activates POMC and inhibits NPY/Agrp neurons.
What effects does the absence of leptin have?
Hyperphagia
Lowered energy expenditure
Sterility
Anti-starvation hormone rather than anti-obesity hormone
Presence of leptin tells the brain that one has sufficient fat reserves for normal functioning- but high leptin has little effect
What is the role of insulin in food intake?
Insulin circulates at levels proportional to body fat.
Receptors in the hypothalamus.
Central administration reduces food intake.
How may insulin coordinate glucose and energy homeostasis?
Insulin regulates blood glucose and body adiposity.
Insulin lowers blood glucose concentration by suppressing its production by the liver and promoting its uptake into ‘insulin-sensitive’ tissues such as muscle and fat.
Insulin also crosses the blood brain barrier to enter the CNS, where it reduces food intake and consequently reduces absorption of glucose and other nutrients into the body.
Glucose-induced insulin secretion from the pancreas increases in proportion to body adiposity, owing to the capability of expanding fat stores to induce resistance to insulin’s glucose-lowering effects.
How does the hypothalamus regulate food intake and body weight?
Food intake balanced with energy expenditure.
Hypothalamus detects leptin, gherkin, PYY and other gut hormones, and has neural input from the periphery and other brain regions.
What is ghrelin?
28aa gastric peptide hormone released from the stomach.
Has a fatty acid group attached- activates the hormone.
Regulates (drives) hunger.
Stimulates NPY/Agrp neurons.
Inhibits POMC neurons.
Increases appetite.
What cell types secretes PYY and GLP-1?
L cells- enteroendocrine cell type in the intestines.
What does PYY3-36 do?
Directly modulates neurons in the arcuate nucleus.
Inhibits NPY release.
Stimulates POMC neurons.
Decreases appetite.
What is glucagon-like peptide-1, and what does it do?
Gut hormone coded for by the preproglucagon gene and released post-prandially.
Well-characterised incretin role in stimulating glucose-stimulated insulin release and also reduces food intake.
What is saxenda?
Long-acting glucagon-like peptide-1 receptor agonist (liraglutide).
Synthetic, modified so can bind to circulating proteins- longer half-life.
Double the dose used for T2DM to treat obesity.
What comorbidities is obesity associated with?
Depression.
Sleep apnoea.
Stroke.
Myocardial infarction.
Hypertension.
Diabetes.
Bowel cancer.
Osteoarthritis.
Peripheral vascular disease.
Gout.
Discuss the thrifty gene hypothesis (James Neel, 1962).
Specific genes selected for to increase metabolic efficiency and fat storage.
In the context of plentiful food and little exercise, these genes predispose their carriers to obesity and diabetes.
Evolutionarily sensible to put on weight.
Thin humans didn’t survive famines, so didn’t pass their genes on to modern humans.
Populations historically prone to starvation become most obese when exposed to Western diet and sedentary lifestyle, e.g. Pima Indians, Pacific Islanders.
