Beyond the Classic Endocrine Glands Flashcards
How is fat considered an endocrine gland?
It is capable of synthesising several hormones such as:
- Leptin: signals satiety to the brain
- Adiponectin: increases insulin sensitivity
- Resistin
- Cytokines
- Androgens
- Oestrogens
Describe the relationship between leptin and obesity.
Mutations of the leptin (LEP) gene in adipose tissue or the leptin receptor (LEPR) gene expressed in the hypothalamus lead to abnormal eating behaviour and the development of early-onset morbid obesity. Leptin deficiency has been successfully treated with leptin, resulting in a reduction in fat mass.
However, LEP mutations are rare, and thus a leptin treatment is only rarely effective.
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.
In healthy adipose tissue:
- leptin signals satiety to the brain
- adiponectin increases insulin sensitivity
- resistin levels low
In obesity:
- leptin secretion is high, but there is resistance to leptin
- adiponectin secretion is low
- insulin resistance, diabetes and metabolic syndrome
- cytokines (eg. IL-6, TNF-α); the normal balance is disturbed
- chemokines (eg. chemotactic cytokines); attract macrophages
What is metabolic syndrome?
It is the general disorder of energy metabolism associated with:
- obesity (especially visceral)
- hypertension
- hyperglycaemia (prediabetes)
- high serum triglycerides (but low HDL)
- insulin resistance
List some differences between visceral or intra-abdominal fat (VS) versus subcutaneous fat (SC).
- VS and SC express different developmental genes
- they have different signalling profiles
- free fatty acids and adipocytokines released from VS fat are drained directly to the liver to alter metabolism
Describe how obesity is a chronic disease.
The body ‘remembers’ its highest body weight and defends this body weight as its ‘new normal weight’.
During weight loss, changes occur in appetite-regulating hormones which increase hunger.
If people with obesity do not eat enough, the hormones trigger the body to conserve energy. These changes in hormones persist for at least 5-10 years following weight loss.
Describe the gut as an endocrine gland.
The 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 and stimulatory pathways in the hypothalamus
APPETITE INHIBITORY:
With increased food intake/ obesity, there is an increase in leptin, insulin, PPY, oxyntomodulin, GLP-1 and CCK. These stimulate POMC/CART neurones, which stimulates the VM (ventromedial) hypothalamus. This results in inhibited food intake (anorexigenic, appetite suppressant).
APPETITE STIMULATORY:
With fasting/ starvation, there is increased ghrelin and decreased leptin. This stimulates AGRP and NPY neurones, which stimulate the L hypothalamus. This 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?
The kidney acts as an endocrine organ and secretes erythropoietin in response to low partial pressures of oxygen in the circulation. This stimulates the production of RBCs.
Describe biological clocks.
Circadian rhythms are driven by the biological clock in the suprachiasmatic nucleus. Other rhythms respond to external daily cues. The suprachiasmatic nucleus produces a 24-hour cycle spontaneously; it 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?
There are nerves that provide neural input to the pineal gland from the retina. It goes from the retina to the suprachiasmatic nucleus (SCN), then to the paraventricular nucleus (PVN), then to the pineal gland (through the superior cervical ganglion).
It (darkness) stimulates the pineal gland to secrete melatonin.
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 have shown that they have a higher prevalence of cancer, psychological disorders, metabolic syndrome, diabetes and cardiovascular disease.
