Beyond the Classic Endocrine Glands Flashcards
How is fat considered an endocrine gland?
Capable of synthesising several hormones such as:
- Leptin: signals satiety to the brain
- Adiponectin: increases insulin sensitivity
- Resistin
- Cytokines
Describe the relationship between leptin and obesity. PART 1
- Mutations of the leptin (LEP) gene in adipose tissue or the leptin receptor (LEPR) gene lead to development of early-onset morbid obesity.
- Leptin deficiency has been successfully treated with leptin, resulting in a reduction in fat mass.
Describe the relationship between leptin and obesity. PART 2
- Obesity is associated with leptin resistance (leptin levels are already high in obesity).
- Multiple interacting pathways control food intake and energy utilisation.
Obesity is regarded as a state of chronic, low-level inflammation.
Expand on this. PART 1
In healthy adipose tissue:
- leptin signals satiety to the brain
- adiponectin increases insulin sensitivity
- resistin levels low
Obesity is regarded as a state of chronic, low-level inflammation.
Expand on this. PART 2
In obesity:
- leptin secretion is high, but there is resistance to leptin
- adiponectin secretion is low
- insulin resistance, diabetes and metabolic syndrome
- adipose tissue expands, secrete chemokines (eg. chemotactic cytokines); attract macrophages
What is metabolic syndrome?
General disorder of energy metabolism associated with obesity, hypertension, hyperglycaemia, high serum triglycerides and insulin resistance
List some differences between visceral or intra-abdominal fat (VS) versus subcutaneous fat (SC).
- VS and SC express different developmental genes
- Different signalling profiles
- FFA and adipocytokines released from VS fat drained directly to liver - alter metabolism
Describe how obesity is a chronic disease. PART 1
- Body ‘remembers’ highest body weight and recognises it as its ‘new normal weight’.
- During weight loss, changes occur in appetite-regulating hormones which increase hunger.
Describe how obesity is a chronic disease. PART 2
- If people with obesity do not eat enough, the hormones trigger the body to conserve energy.
Describe the gut as an endocrine gland.
Gastroenteropancreatic tract is the largest endocrine gland in the body.
The incretin hormones:
- GIP (glucose-dependent insulinotropic peptide)
- GLP-1 (glucagon-like peptide 1)
Which three stimuli can signal the hypothalamus regarding regulation of food uptake?
- hormones secreted by the stomach and intestines
- vagal afferents to the nucleus of the tractus solitarius
- leptin secreted from adipocytes
In response to different stimuli, describe the appetite inhibitory pathway in the hypothalamus
- With increased food intake/ obesity, increase in leptin, insulin, PPY, oxyntomodulin, GLP-1 and CCK.
- Stimulate POMC/CART neurones, which stimulates the ventromedial hypothalamus.
- Results in inhibited food intake (anorexigenic, appetite suppressant).
In response to different stimuli, describe the appetite stimulatory pathway in the hypothalamus
- With fasting/ starvation, there is increased ghrelin and decreased leptin.
- Stimulates AGRP and NPY neurones, which stimulate the L hypothalamus.
- Results in increased food intake.
List some other ‘non-classical’ endocrine organs.
- heart
- kidney
- bone
- tumours
- pineal gland
How does the kidney stimulate the production of RBCs?
- Secretes EPO in response to low partial pressures of oxygen in the circulation.
- Stimulates the production of RBCs.
Describe biological clocks. PART 1
- Circadian rhythms are driven by the biological clock in the suprachiasmatic nucleus (SCN) above optic chiasm
- Other rhythms respond to external daily cues.
- SCN produces a 24-hour cycle spontaneously
Describe biological clocks. PART 2
- SCN affects melatonin, cortisol and core-body temperature.
- Circadian rhythms are not entrained to the light-dark cycle; so the day-night cycle doesn’t cause the rhythm, it simply corresponds to the rhythm.
How is the pineal gland thought to measure time?
- Nerves that provide neural input to the pineal gland from the retina.
- Goes from the retina to SCN) then to paraventricular nucleus (PVN), then to pineal gland (through the superior cervical ganglion).
- Darkness stimulates pineal gland to secrete melatonin. Light inhibits
What is the proof of the different effects of melatonin when dysregulated?
- Epidemiological studies in (for example) shift workers, long-distance flight crews and patients with sleeping disorders
- Higher prevalence of psychological disorders, metabolic syndrome, and CVS disease.
What are the steps in the synthesis of melatonin?
→L- tryptophan
→ Serotonin
→ Melatonin
What is recombinant EPO used for?
→ Treat anaemia due to renal failure
→ Blood doping agent
What does GLP do?
→ Potentiates insulin secretion in response to rising plasma glucose
→ Reduces appetite
What is GIP stimulated by?
→ Presence of fat and glucose in the small intestine
What does GIP do?
→ Inhibits gastric secretion and motility
→ potentiates release of insulin from beta cells in response to high blood glucose levels
What does ghrelin do?
→ strong stimulant for feeding and appetite
→ Stimulates growth hormone
What is secretin stimulated by?
→ Acidic pH in the lumen of the small intestine
What does secretin do?
→ Stimulates secretion of water and bicarbonate from the pancreas and bile ducts
What does CCK do and what is it stimulated by?
→ Stimulates secretion of pancreatic enzymes
→ Contraction of the gall bladder and emptying
→ Stimulated by presence of fatty acids and amino acids in small intestine
What does gastrin do and what is it stimulated by?
→ Stimulates gastric acid secretion
→ Stimulated by peptides and amino acids in gastric lumen
What is leptin released from?
Adipose tissue
Why is adipose tissue needed?
→ If fat was allowed to accumulate it would be toxic
→ Lipotoxicity
What is glucose converted to when it can no longer be stored as glycogen?
→ converted into fat
→ Stored in larger quantities
What happens when the body has excess fat and needs to store it?
→ Insulin stimulates LPL to break down TG into FFA
→ FFA enter the cell
What happens when the body needs fat for energy?
→ HSL (hormone sensitive lipase) breaks down fat stored as triglycerides
→ Adrenaline, glucagon,cortisol and GH stimulate this
What happens when free fatty acids are in the cell?
→ Become triglycerides again
What is the main source of triglycerides?
→ Chylomicrons from digestion
→ VLDL
What are free fatty acids bound to?
Albumin
How do triglycerides get inside cells?
→ As free fatty acids
→ hydrolyzed by lipoprotein lipase
What is the main function of adipocytes?
→ Store energy as triglycerides
→ Release them as free fatty acids
