Metabolism and growth Flashcards
Growth
Implies development from the time of birth/ conception(?) to the time of maturity.
Generally implies increase in size resulting from cell multiplication and cell expansion, as well as maturation of tissues.
Obesity
Excess body fat has accumulated to the extent that it may have a negative effect on health.
Malnutrition
Results from eating a diet in which one or more nutrients are either not enough or too much such that the diet causes health problems.
Malnutrition often refers to undernutrition, however can refer to overnutrition
When does prenatal growth occur?
From conception to birth
What hormones are important for foetal growth?
Insulin, insulin like growth factors (IGF-1), and GH/ placental GH to a lesser extent.
What is the most important factor that drives foetal growth?
Substrate delivery from the mother is the most important factor
What is post-natal growth?
From birth to adulthood.
How much does mass increase in post-natal growth?
20 fold
Major determinants of post natal growth are…
Major determinants include hormones (GH, action via IGF1/2, thyroid hormones, sex steroids), genetic (parents height), socio-economic factors, chronic disease and psychological factors.
Why are infants of diabetic mothers at risk?
Maternal hyperglycaemia leads to foetal hyperinsulinemia (as leads to stimulation of IGF-1 production and deposition of adipose tissue). Therefore foetus has increased fat deposits, length and lean body mass.
What is the cause of leprechaunism?
Insulin receptor failure - leads to severe dwarfism.
What does pancreatic agenesis have on infant?
Neonatal diabetes - average 50% reduction in body weight
What is Beckwith-Wiedemann syndrome?
Excessive IGF2 production and somatic overgrowth
What can issues in foetal growth lead to?
Leads ti abnormal physiological responses and predisposing to later diseases. Possible related to altered hormonal sensitivity resulting in resetting of homeostatic circuits to a different level.
IGF1 role?
Growth following birth
IGF2 role?
Gestational growth
Insulin role
Insertion of GLUT4 into cells for glucose uptake
GH role
Variety of actions
Increase IGF secretion from liver
Increase protein synthesis
Decrease glucose uptake into adipose and increase lipolysis
Decrease of glucose uptake into muscle and increase amino acid uptake
Human placental lactogen role
Modifies the metabolic state of the mother during pregnancy to facilitate the energy supply of the foetus.
Decreases maternal insulin sensitivity to increase maternal blood glucose.
Decreases maternal glucose utilisation, and increases lipolysis to free fatty acids for availability to the mother, so that relatively more glucose can be utilised by the foetus.
What releases HPL?
Placenta
HPL effect on glucose and insulin
Decrease insulin sensitivity, decrease maternal blood glucose utilisation
What overall changes occur in chronic malnutrition?
The body must maintain substrate supplies for vital functions, divert protein synthesis away from muscle to liver, supress general growth to maintain function
What hormones control changes in chronic malnutrition?
GH/IGF1 and thyroid hormones
Reduced fasting insulin and a subnormal insulin response to a glucose load - slight glucose intolerance.
This diverts amino acids from muscles to other tissues (esp liver) for glycogenesis and protein synthesis.
How are amino acids diverted to liver in starvation (which hormone has main effect)?
Cortisol
What happens to GH in starvation
Large increase
What happens to GH sensitivity in starvation?
GH resistance, high GH, low IGF
What happens to IGF in starvation?
Falls
What does low IGF mean in starvation?
Enhanced lipolysis, and low levels of IGF1 suppress general protein synthesis and growth.
What is a good indicator of starvation/malnutrition?
IGF1
Marasmus
More common form of protein-caloric malnutrition.
Leads to muscle wasting with no oedema, lows of adipose tissue (heart brain and liver least affected), low blood glucose, ketosis, reduced BMR, reduced plasma insulin, impaired immunity.
Kwashiokor
Generalised oedema with areas of pigmentation, child is withdrawn and will not eat, thin discoloured hair, hepatomegaly with fatty degeneration, diarrhoea, not necessarily underweight
Reduced albumin, VLDL synthesis, reduced plasma branched chain FA
Associated with relatively higher carbohydrate intake: foods with low protein/energy ratio.
Carbohydrate stimulates insulin secretion and increased muscle protein synthesis at expense of liver.
Marasmus vs Kwashiokor muscle
Higher carbohydrate intake in kwashiokor - higher insulin secretion - increases muscle protein synthesis at liver expense
Lower carb in marasmus - muscle wasting
What controls our body weight regulation?
Hypothalamus
What is the role of adipose?
A dynamic buffer of circulating fatty acids and triglycerides. It’s buffer function gives control of storage and mobilisation required to maintain insulin sensitivity
What hormone does adipose release?
Leptin
Role of leptin
Produced by adipose cells and enterocytes in the small intestine to regulate food intake by inhibiting hunger (acts on POMC/CART neurons in the arcuate - alpha MSH to ventromedial nuclei/ PVN in the hypothalamus) - raises metabolism (in turn diminishes fat storage in the adipocytes) and depletes appetite
Where is adiponectin produced and what is its role?
Produced primarily from adipose: reduces hepatic glucose production and increases muscle glucose utilisation.
Increases insulin sensitivity
Anti-inflammatory adipokine
What is acylation stimulating protein?
Acts locally on adipocytes to increase triglyceride formation by increasing glucose uptake and triglyceride synthesis.
Has an additive effect with insulin. Suppresses lipolysis and FA release.
Adiponectin in obesity
Levels are reduced in obesity.
ASP in obesity?
Levels are increased in obese humans.
Visceral fat vs subcutaneous fat
Located within the abdominal wall whereas subcutaneous fat is located beneath the skin but above the abdominal muscle wall.
Visceral fat has recently been discovered to be a significant producer of hormones, particularly those involved in inflammatory tissue responses.
What is likely to drive obesity? Treating it endocrinologically?
Leptin resistance or deficiency
What is likely to drive obesity? Treating it as an inflammatory disease?
Obese adipose tissue secretes various inflammatory cytokines (IL6, TNFalpha) and dysregulation of anti-inflammatory adipokines (e.g. adiponectin) - leads to disease.
How do obesity and type II diabetes have dual pathology?
TNF alpha from adipocyte inflammation partially blocks insulin signalling via interference with intracellular signal transduction pathways and decreased GLUT4 transporters.
Leads to insulin resistance (inability of cells to respond adequately to normal levels of insulin) - beta cells produce insufficient insulin and the liver inappropriately releases glucose into the blood - loss of beta cells due to apoptosis.
The plasma concentration of this hormone is a sensitive marker of chronic malnutrition
IGF-1
A hormone which increases insulin sensitivity
Adiponectin
Deficiency of this hormone is a rare cause of morbid hyperphagia and obesity
Leptin
The major site in the body for the regulation of energy balance
Hypothalamus
A molecule which contributes significantly to insulin resistance in obesity
TNF alpha
Release of growth hormone is inhibited by each of the following
Somatostatin (GHIH), Circulating GH, circulating IGF1, hyperglycemia, glucocortocids, dihydrotestosterone
Release of growth hormone is stimulated by
Somatocrinin (GHRH), Ghrelin, androgens, oestrogen, hypoglycaemia, REM sleep, fasting, vigorous exercise
