Beyond the Classic ENdocrine Glands Flashcards
What are the hormones in adipose tissues?
The hormones in the adipose tissue:
Lipoprotein lipase (LPL):
-Triglyceride hydrolysis (lipolysis)
-Involved in receptor-mediated lipoprotein uptake
Hormone-sensitive lipase (HSL):
-When needed, fat stored as triacylglycerol (TG) is hydrolysed for energy use and released into circulation
How does fat act as an endocrine gland?
Various other molecules are actually synthesised and released by adipose tissue
Adipose tissue contains aromatase enzymes which can convert androgens to oestrogen
There are various more cytokines and other molecules that have been discovered to be released by adipose tissue:
Cytokines are released for local signalling but its still a blur between paracrine and endocrine
Leptin is synthesised and secreted by adipocytes, involved in a negative feedback loop with fat storage
Signals satiety to the brain as fat stores build up (stop eating)
Adiponectin increases insulin sensitivity
Resistin function not fully known but correlated with insulin resistance
How are leptin and obesity linked?
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 leptin treatment 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.
What is obesity?
Obesity is regarded as a state of chronic, low-level inflammation
The balance of signalling molecules is thrown off balance in obesity
Healthy adipose tissue:
Leptin signals satiety to the brain
Adiponectin increases insulin sensitivity
Resistin levels low
In obesity:
Leptin secretion high but resistant to leptin
Adiponectin secretion low
Insulin resistance, diabetes, and metabolic syndrome
Cytokines (e.g., IL-6, TNF-α)- Normal balance disturbed
Chemokines (chemotactic cytokines)- Attract macrophages
How could obesity cause inflammation?
There are a number of theories
One is that it may be related to hypoxia
As adipose tissue mass expands you generate new adipocytes but as well as that the existing adipocytes expand in volume because adipocytes store TG as a single droplet
So there will be a greater diffusion distance between adipocytes and capillaries
So metabolic changes associated with hypoxia may be one factor associated with inflammatory factors
Another possible explanation is to do with metabolic stress in the mitochondria, ER or both
This is due to the increased load of nutritional processing over nutrition
Another possibility is to do with visceral adipose tissue
Visceral adipose tissue’s blood supply will drain into the portal vein so that means that the signalling molecules from them will hit the liver first
Given this signalling to the liver many of these metabolic changes could be indirectly mediated via adipose tissue signalling adipose tissue interaction
What are the general disorders of energy metabolism associated with?
- Obesity (especially visceral) or a particular waist diameter
- Hypertension
- Hyperglycaemia (prediabetes)
- High serum triglycerides (but low HDL)
- Insulin resistance
How does the distribution of adipose tissue make a difference?
Visceral (VS) or intra-abdominal fat versus subcutaneous (SC) fat
Visceral adipose tissue is more strongly correlated with the negative effects of obesity than subcutaneous adipose tissue which in women is stored in the thighs and hips
VS and SC fat express different developmental genes
Different signalling profiles
Free fatty acids and adipocytokines released from VS fat drain directly to liver to alter metabolism
Why is it hard to lose weight as an obese person?
The body fights weight loss for people with obesity:
The body “remembers” its highest body weight and defends this body weight as the 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
Changes in hormones persist for at least 5-10 years following weight loss
How does the gut act as an endocrine organ?
Gastroenteropancreatic tract is the largest endocrine gland in the body
The incretin hormones:
GIP, also known as glucose-dependent insulinotropic peptide
GLP-1 (glucagon-like peptide 1)
There are many hormones which are secreted by parts of the GI tract
What are the appetite inhibitory and stimulatory pathways in the hypothalamus?
If you stimulate the ventromedial hypothalamus (the POMC/CART neurones) you supress food intake so it is anorexigenic
POMC is the initial gene product that is cleaved to produce ACTH
Activated by leptin, insulin, GLP-1, CCK etc.
If you stimulate the lateral hypothalamus it stimulates food intake o it is orexigenic
Contain neurones using NPY and AGRP
Activated by ghrelin increase and leptin decrease
How does the kidney act as an endocrine organ?
The kidney as an endocrine organ – secretion of erythropoietin in response to low partial pressure of oxygen in the circulation.
Stimulates the production of erythrocytes
Recombinant EPO can be used to treat anaemia due to renal failure, in critical illnesses and as a blood doping agent for endurance sports (although this would be disqualifying)
What is the biological clock?
Circadian rhythms are driven by the biological clock in the suprachiasmatic nucleus
Various circadian rhythms are under this nucleus’s control
Other rhythms respond to external daily cues
What are the rhythms driven by?
Plasma melatonin:
Melatonin is secreted by the pineal gland
Controlled by the SCN
The daily variation in the SCN is passed on to the pineal gland through a multi-step pathway
How does the pineal gland measure time?
Neural inputs to the pineal
from retina-> SCN
-> superior cervical ganglion
-> pineal gland
Synthesis of melatonin:
Darkness is the signal that stimulates melatonin production
There are direct projections from the retina to the SCN
These neural inputs are from a special class of retinal ganglion cells that don’t take in visual perception just overall light levels
During the day the firing of from those neural inputs inhibits the production of melatonin but as it gets darker the inhibition fades away
L-tryptophan —-> serotonin —> melatonin
How does disturbance of the circadian rhythm affect people?
Rhythms out of synchrony with dark/ light cycle
Epidemiological studies in, for example shift workers, long-distance flight crews and patients with sleep disorders have shown that they have a higher prevalence of cancer, psychological disorders, metabolic syndrome, diabetes and cardiovascular diseases.
